Published online: 2020-06-17 Original article Educational nurse-led telephone intervention shortly before colonoscopy as a salvage strategy after previous bowel preparation failure: a multicenter randomized trial Authors Marco Antonio Alvarez-Gonzalez 1, 2, 3, Miguel Ángel Pantaleón Sánchez 1, 2, Belén Bernad Cabredo 4, Ana García- Rodríguez 5, Santiago Frago Larramona 6, Oscar Nogales 7, Pilar Díez Redondo8, Ignasi Puig del Castillo9, Cristina Romero Mascarell10, Noemí Caballero11, Iván Romero Sánchez-Miguel 12, Rocío Pérez Berbegal1, Domingo Hernández Negrín13, Gema Bujedo Sadornill 4, Alicia Pérez Oltra 5, Gemma Casals Urquiza1, Jaume Amorós Martínez14, Agustín Seoane Urgorri 1, 3, Inés Ana Ibáñez Zafón 1, Antonio Z. Gimeno-García 13 Institutions © 2020. The Author(s). 1 Department of Digestive Diseases, Hospital del Mar, This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying Barcelona, Spain and reproduction so long as the original work is given appropriate credit. Contents 2 Department of Medicine, Universitat Autònoma de may not be used for commecial purposes, or adapted, remixed, transformed or Barcelona, Barcelona, Spain built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) 3 IMIM, Hospital del Mar Medical Research Institute, Barcelona, Spain G R A P H I C A L ABS T R AC T 4 Department of Digestive Diseases, Hospital Universitario de Burgos, Burgos, Spain Successful bowel Successful bowel 5 Department of Digestive Diseases, Hospital de preparation (ITT analysis) preparation (PP analysis) Viladecans, Barcelona, Spain 100% 100% 6 Department of Digestive Diseases, Hospital Santa P = 0.12 P = 0.001 Bárbara, Soria, Spain 90% 90% 7 Department of Digestive Diseases, Hospital Gregorio 80% 80% Marañón, Madrid, Spain 8 Department of Digestive Diseases, Hospital del Rio 70% 70% 77,3% 83,5% Hortega, Valladolid, Spain 60% 72% 60% 72% 9 Department of Digestive Diseases, Altahia Xarxa Asistencial Universitaria de Manresa, Barcelona, Spain 50% 50% 10 Department of Digestive Diseases, Consorci Sanitari de Control (n = 329) Control (n = 329) Terrassa, Barcelona, Spain Intervention (n = 322) Successful call (n = 267) 11 Department of Digestive Diseases, Hospital Germans ARD1 5.3 % ARD1 11.5 % Trias i Pujol, Badalona, Spain (95%CI) (−1.4 % to 12 %) (95%CI) (4.9 % to 18.1 %) 12 Department of Digestive Diseases, Hospital 12 de NNT2 19 P-value 0.001 Octubre, Madrid, Spain Multicenter RCT: Our reinforced education did 13 Department of Digestive Diseases, Hospital 657 patients with inadequate not result in a significant Universitario de Canarias, La Laguna, Spain bowel preparation improvement in bowel 14 Open University of Catalonia, Barcelona, Spain preparation. We evaluated a nurse-led education by phone close to In the 83 % of cases where the submitted 24.12.2019 endoscopy appointment as a patient was contactable and accepted after revision 22.4.2020 salvage strategy focused on received the intervention, bowel published online 17.6.2020 these difficult-to-prepare preparation significantly patients. improved. Bibliography 1 ARD, Absolute Risk Difference. 2 NNT, Number Needed to Treat Endoscopy 2020; 52: 1026–1035 DOI 10.1055/a-1178-9844 ISSN 0013-726X 1026 Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). Supplementary material Methods We performed a multicenter, endoscopist-blind- Online content viewable at: ed, randomized controlled trial. Consecutive outpatients https://doi.org/10.1055/a-1178-9844 with previous inadequate bowel preparation were enrolled. Both groups received the same standard bowel preparation Scan this QR-Code for the author commentary. protocol. The intervention group also received reinforced education by telephone within 48 hours before the colonos- copy. The primary outcome was effective bowel prepara- tion according to the Boston Bowel Preparation Scale. In- tention-to-treat (ITT) analysis included all randomized pa- tients. Per-protocol analysis included patients who could be contacted by telephone and the control cases. Results 657 participants were recruited by 11 Spanish hos- Corresponding author pitals. In the ITT analysis, there was no significant difference Marco A. Álvarez-González, MD, PhD, Department of between the intervention and control groups in the rate of Digestive Diseases, Hospital del Mar de Barcelona, Passeig successful bowel preparation (77.3 % vs. 72 %; P = 0.12). In Marítim de la Barceloneta, 25–29, 08003 Barcelona, Spain the intervention group, 267 patients (82.9 %) were contac- Fax: +34-93-2483254 ted by telephone. Per-protocol analysis revealed signifi- marcoalgo@gmail.com cantly improved bowel preparation in the intervention group (83.5 % vs. 72.0 %; P = 0.001). ABSTR AC T Conclusion Among all patients with previous inadequate Background The most important predictor of unsuccess- bowel preparation, nurse-led telephone education did not ful bowel preparation is previous failure. For those patients result in a significant improvement in bowel cleansing. with previous failure, we hypothesized that a nurse-led edu- However, in the 83 % of patients who could be contacted, cational intervention by telephone shortly before the colo- bowel preparation was substantially improved. Phone edu- noscopy appointment could improve cleansing efficacy. cation may therefore be a useful tool for improving the quality of bowel preparation in those cases. Introduction social media applications [11 – 13]. International guidelines [8, The quality of bowel preparation represents a key factor affect- 14] recommend the use of enhanced instructions for bowel ing the efficacy of colonoscopy. The European Society of Gastro- preparation, although there is no consensus on which educa- intestinal Endoscopy recently raised the quality threshold for tional tool is the best or how to implement it. Furthermore, adequate bowel preparation to ≥ 90 % [1]. However, in clinical there are no studies that specifically address the usefulness of practice, between 20 % and 30 % of patients do not achieve suc- repeated instructions in patients after previous bowel prepara- cessful bowel preparation [2]. Inadequate bowel cleansing re- tion failure; reinforced education for bowel preparation may re- sults in harmful consequences, such as aborted procedures, present an effective tool to improve compliance with instruc- missed lesions, diagnostic delays, and increased risks and tions in these patients. healthcare costs [3, 4]. A history of unsuccessful bowel prepara- The aim of this study was to evaluate the effectiveness of a tion represents the most relevant predictor for inadequate bow- nurse-led educational intervention by telephone shortly before el preparation [5]. A retrospective study showed that more than the colonoscopy appointment as a salvage strategy to improve 23 % of patients with previous inadequate bowel preparation bowel cleansing after previous bowel preparation failure. also failed to achieve successful bowel cleansing in repeat pro- cedures and could be considered a difficult-to-treat patient Methods group [2, 6, 7]. Unfortunately, the best approach for patients Study design with failed bowel preparation has not yet been determined [8]. Modifiable and nonmodifiable factors affect the quality of A prospective, multicenter, endoscopist-blinded, randomized bowel preparation. Among the modifiable risk factors, patient controlled trial (RCT) was conducted to determine whether an adherence to instructions plays a leading role in achieving ade- educational intervention may increase bowel preparation suc- quate bowel cleansing [9]. Few medical explorations require so cess after previous bowel preparation failure. The study was rigorous and complex a preparation as bowel cleansing, so it performed between January 2017 and June 2018, and was con- may be considered a major barrier for some patients undergo- ducted in 11 tertiary hospitals in Spain, with the Hospital del ing colonoscopy [10]. Mar of Barcelona being the coordinating center. The study pro- In recent years, multiple strategies to reinforce patient edu- tocol was approved by the ethics committee of the coordinat- cation have demonstrated improved bowel cleansing quality, ing center (6605/l) and the recruiting centers. We followed such as visual aids, face-to-face sessions, telephone and short the Declaration of Helsinki ethical guidelines and registered message service (SMS) communications, and smartphone and Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). 1027 Original article the study protocol at ClinicalTrials.gov (NCT03055689). Writ- centralized at the coordinating center (Hospital del Mar de Bar- ten informed consent was obtained from all enrolled patients. celona) and were conducted by two trained endoscopy nurses. The main purpose of the telephone intervention was to rein- Study population, treatment allocation, and force the instructions of the bowel preparation based on three masking aims: 1) to ensure compliance with the low-fiber diet and the Consecutive outpatients aged 18 – 85 years with previous in- laxative intake protocol in terms of both timing and dose; 2) to adequate bowel cleansing according to the Boston Bowel Prep- emphasize the importance of properly performing the bowel aration Scale (BBPS) [15] were invited to participate. We includ- preparation protocol to guarantee adequate visualization and ed patients with any indication for colonoscopy, such as surveil- detection of concerning lesions; and 3) to clarify any patient lance, diagnosis, and screening. Exclusion criteria included the doubts about the bowel preparation protocol. The content of inability to follow instructions or to use a telephone, including the call was the same as the standard education given in the hearing problems, unwillingness to participate, severe renal booklet to both groups (see Appendix 1s in the online-only impairment, active inflammatory bowel disease, pregnancy or supplementary material). breastfeeding. Consenting patients were randomized into blocks of six indi- Outcome measures viduals in each center using a computer-generated block ran- The primary outcome was the rate of successful bowel prepara- domization table with a 1:1 allocation rate to the control group tion, as measured by the BBPS [20]. Success was defined as all and the intervention group. A colonoscopy appointment was colon segments scoring ≥ 2 points. Missing efficacy data due scheduled for within 3 months. A research nurse provided bow- to nonattendance at the colonoscopy appointment were impu- el preparation instructions and self-administered question- ted as bowel preparation failures. In patients with partial co- naires. The patients were asked to provide at least two tele- lectomy or an incomplete colonoscopy due to a stricture, bowel phone numbers for themselves or their family members so preparation success was defined when all evaluable segments that the nurses could contact them. In all case, the nurse-led had ≥ 2 points. Similarly, bowel preparation failure was record- education was always addressed to the patient directly. ed when one or more segments had a rating < 2 points. Skilled endoscopists (> 1000 colonoscopies each) who were Secondary end points included the BBPS scale for patients in blinded to the randomization rated the bowel cleansing using whom the colonoscopy was performed, complete colonoscopy the BBPS. Before starting the study, all endoscopists underwent rate, overall and proximal (to the splenic flexure) colon lesions a calibration exercise to improve consensus and minimize inter- detected, such as adenomas and serrated lesions. Additional observer variability. All colonoscopies were performed under secondary outcomes, which were planned a priori but not listed deep sedation. Following guideline recommendations, seda- in the registered protocol at ClinicalTrials.gov, were attendance tion was administered by a gastroenterologist, or by an anes- at the colonoscopy appointment, adherence to the diet and thesiologist in patients with risk factors [16]. laxative intake, cancer, mean adenoma per patient, and adeno- mas or serrated lesions in the distal colon. Standard bowel preparation protocol Both groups received the same bowel preparation protocol Data collection based on international guideline recommendations [14, 17]. We recorded variables known to potentially impact bowel First, all participants received standard education, which con- cleansing [2, 7, 21, 22]. Before the colonoscopy, all participants sisted of a face-to-face visit by an endoscopy nurse who provid- completed self-administered questionnaires relating to the diet ed verbal and written instructions detailed in a booklet. The and laxative intake protocol. booklet was the same for all centers and was written in plain At the colonoscopy appointment, an investigator collected language and with some pictures to facilitate the understand- the questionnaires. After the procedure, endoscopists, who ing of the instructions. Second, a low-fiber diet was implemen- were blinded to the intervention allocation, registered the bow- ted 7 days before the colonoscopy, as this diet has been shown el cleansing quality and any relevant information regarding de- to be better tolerated and may be more effective than a clear tected lesions. Research electronic data capture (REDcap), a se- liquid diet [18]. We also recommended a discontinuation of cure web application, was used to collect and manage all data oral iron treatment 7 days before the colonoscopy. Finally, a collected from the 11 hospitals. split-dose laxative regimen was instructed, with the second dose starting 5 hours before the colonoscopy. A total of 4 L of Statistical analysis polyethylene glycol (PEG) was chosen as the laxative, according The sample size was estimated to demonstrate the superiority to a previous publication [19]. of the educational intervention. Using an estimated bowel preparation success rate of 70 % for the control group, we cal- Reinforced educational intervention culated a 10 % improvement with the intervention, with an α- In addition to the standard bowel preparation protocol, the inter- risk of 0.05, 80 % power, and a dropout rate of 10 %, resulting vention group received reinforced education via a nurse-led tele- in 326 patients per arm. phone call within 24 – 48 hours prior to the colonoscopy appoint- The intention-to-treat (ITT) analysis included all randomized ment. To ensure consistency of the intervention, all calls were patients. The per-protocol analysis compared outcomes in pa- 1028 Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). n = 657 Randomized 2 canceled colonoscopy 4 canceled colonoscopy n = 329 n = 322 ITT Control group Intervention group n = 55 (17 %) Patients whose telephone intervention failed n = 329 n = 267 (83 %) PP Control group Patients successfully contacted by telephone ▶ Fig. 1 Flow-chart of the study. ITT, intention to treat; PP, per protocol. tients who were successfully contacted by telephone and the ican Society of Anesthesiologists score, with more class I pa- control group. tients in the control group. There were no significant differen- Three post-hoc analyses were conducted. First, we analyzed ces between the two groups in terms of the initial failed colo- bowel preparation success according to several risk factors; noscopy (▶ Table 1). The median waiting time from the sche- Bonferroni correction was performed for significant P values. duling visit to the colonoscopy was 30 days in both groups. Second, we analyzed telephone contact availability in the inter- vention group. Finally, an economic analysis was developed to Primary outcome quantify the direct costs of the telephone intervention compar- In the ITT analysis, the rate of successful bowel preparation was ed with the cost of an unsuccessful bowel preparation. The not significantly higher in the telephone group than in the con- average cost of the telephone intervention was based on the trol group (77.3 % vs. 72.0 %; P = 0.12); the absolute risk differ- 2019 Hospital del Mar collective agreement. The hourly cost of ence (ARD) was 5.3 % (95 %CI – 1.4 % to 12.0 %) and the number a trained nurse was €33. We assumed that an unsuccessful needed to treat (NNT) was 18.9 cases (▶ Table 2). bowel preparation in a public health system would result in the The per-protocol analysis revealed a significantly higher bow- loss of opportunity for a valid colonoscopy. The cost of a colo- el preparation success rate in the intervention group (83.5 % vs. noscopy was obtained from the Public Health System of Catalo- 72.0 %; P = 0.001), with an ARD of 11.5 % (95 %CI 4.9 % to 18.1 %) nia [23] and was estimated to be in €320. (▶ Table 2). The qualitative variables were compared between groups by the Pearson’s chi-squared test or Fisher’s exact test if applicable. Secondary outcomes Continuous variables are expressed as the means with 95 % con- In the ITT analysis, there were no significant differences be- fidence intervals (CIs) and were compared using Student’s t tween the groups in the colonoscopy attendance rate. Bowel test. Two-tailed P values of < 0.05 were considered statistically cleansing adequacy in patients who underwent colonoscopy significant. Stata software version 15.1 (StataCorp LLC, College was not significantly different between the groups for all three Station, Texas, USA) was used by our research statistician to colon segments or in the right colon, but there was a trend to- perform the analysis. ward better cleansing adequacy in the transverse and left colon in the telephone group. There was also a trend toward a better Results complete colonoscopy rate in the telephone group. There were no differences in adherence to the diet, laxative intake or the Patient characteristics interval between the last dose and the colonoscopy between A total of 657 outpatients with previous inadequate bowel prep- the groups (▶ Table 2). aration were recruited. After randomization, six patients can- In the per-protocol analysis, there was significantly better celed their colonoscopy appointment. Finally, 329 individuals colonoscopy attendance in the telephone group. Segmental in the control group and 322 in the intervention group were in- bowel cleansing was significantly better in the left colon, and cluded in the ITT analysis. The research nurses successfully con- there was a trend toward more adequate cleansing globally tacted 267 (82.9 %) patients in the telephone group and these and in the right and transverse colon. There was also a signifi- patients were included in the per-protocol analysis (▶ Fig. 1). cantly higher rate of a complete colonoscopy. Comparison of the baseline characteristics between the con- There were no differences in the adenoma detection rate, trol and intervention groups showed an imbalance in the Amer- but there were more patients with multiple adenomas and ser- Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). 1029 Original article ▶ Table 1 Baseline characteristics of the patients regarding the initial ▶ Table 1 (Continuation) failed colonoscopy. Variable Control Telephone P Variable Control Telephone P (n = 329) (n = 322) value (n = 329) (n = 322) value ▪ Oral 30 (9.1) 31 (9.6) Interval, median (IQR), days 30 (44.5) 30 (39) 0.92 ▪ Written 184 (55.9) 183 (56.8) Age, median (IQR), years 63.7 (17.6) 64.4 (15.7) 0.38 ▪ Oral and written 112 (34.3) 108 (33.5) Male sex, n (%) 185 (56.2) 179 (55.6) 0.87 Morning schedule, n (%) 235 (71.4) 216 (67.1) 0.30 BMI, median (IQR) 27.1 (5.3) 26.7 (7.1) 0.93 Medical education provider, n (%) 0.54 Diabetes mellitus, n (%) 79 (24.0) 61 (18.9) 0.12 ▪ Nurse 93 (28.3) 87 (27.0) Abdominal/pelvic surgery, 138 (41.9) 135 (41.9) 0.99 n (%) ▪ Physician 101 (30.7) 104 (32.3) Partial colectomy, n (%) 35 (10.6) 30 (9.3) 0.52 ▪ Secretary 133 (40.4) 131 (40.7) Constipation, n (%) 123 (37.4) 125 (38.8) 0.78 Complete colonoscopy rate, 170 (51.7) 165 (51.2) 0.91 n (%) Tricyclic antidepressants, 28 (8.5) 32 (9.9) 0.53 n (%) IQR, interquartile range; BMI, body mass index; ASA, American Society of Anesthesiologists; MCSP, magnesium citrate plus sodium picosulfate; PEG, Calcium blockers, n (%) 27 (8.2) 20 (6.2) 0.33 polyethylene glycol. Medical conditions associated with poor bowel cleansing but affecting < 5 % Opiates, n (%) 14 (4.3) 17 (5.3) 0.54 of patients (cirrhosis, stroke, severe renal impairment, Parkinson disease or dementia) are not represented. Illiteracy, n (%) 7 (2.1) 6 (1.9) 0.81 ASA class, n (%) 0.04 ▪ I 133 (40.4) 100 (31.1) rated lesions in the telephone group (▶ Table 3). There was also a trend toward a higher distal adenoma detection rate and ▪ II 171 (52.0) 193 (59.9) mean adenoma per patient in the telephone group (▶ Table 3). ▪ III 25 (7.6) 29 (9.0) For patients randomized to the intervention group, we com- pared patients who were successfully contacted with those who Indication, n (%) 0.81 were impossible to reach (Table 1s). There were no significant ▪ Screening 87 (26.4) 85 (26.4) differences in their baseline characteristics. ▪ Surveillance 96 (29.2) 95 (29.5) Analysis of bowel preparation success according to several risk factors revealed that the telephone intervention was parti- ▪ Diagnostic 145 (44.1) 142 (44.1) cularly effective when the indication for the colonoscopy was Referring physician, n (%) 0.31 symptoms. In contrast, we could not show any improvement in ▪ Gastroenterologist 76 (23.1) 74 (23.0) patients with diabetes mellitus, constipation or without ab- dominal or pelvic surgery (▶ Table 4). ▪ Primary care 187 (56.8) 199 (61.8) Regarding the cost-effectiveness analysis, the mean dura- ▪ Other specialties 65 (19.8) 49 (15.2) tion of the telephone intervention was 8.1 minutes. The mean First colonoscopy, n (%) 143 (43.5) 155 (48.1) 0.13 cost of the nurse-led telephone intervention was €5.1, includ- ing 15 % of nonpersonnel costs. Considering an NNT of 18.9 Laxative, n (%) 0.51 telephone calls to prevent one bowel preparation failure, €96 ▪ MCSP 94 (28.6) 87 (27.0) would be spent in preventing one failure. Therefore, the imple- ▪ PEG + ascorbate, 2 L 99 (30.1) 82 (25.5) mentation of the nurse-led telephone education would be cost- effective, saving €224 per bowel preparation failure. ▪ PEG ,4 L 128 (38.9) 143 (44.4) Dosing, n (%) 0.72 Discussion ▪ Split dose 2 days 208 (63.2) 207 (64.3) This is the first multicenter trial to assess an educational inter- ▪ Split dose same day 33 (10.0) 28 (8.7) vention for improving bowel preparation in patients at high risk ▪ Day before 85 (25.8) 86 (26.7) of poor bowel cleansing. In the whole group (ITT analysis), a Interval ≤ 5 hours, n (%) 174 (52.9) 164 (50.9) 0.53 telephone interview conducted by a trained nurse 24 – 48 hours before the colonoscopy did not show any significant benefit in Instructions, n (%) 0.56 bowel preparation quality in patients with previous bowel prep- aration failure. However, in patients who could actually be con- tacted by telephone and who received the educational inter- 1030 Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). ▶ Table 2 Outcome measures in the intention-to-treat and per-protocol analyses. Variable Control (n = 329) Telephone (n = 322) ARD (95 %CI) P value Successful bowel preparation, n/N (%) ▪ ITT 237/329 (72.0) 249/322 (77.3) 5.3 (–1.4 to 12.0) 0.12 ▪ PP 237/329 (72.0) 223/267 (83.5) 11.5 (4.9 to 18.1) 0.001 Colonoscopy attendance, n/N (%) ▪ ITT 302/329 (91.8) 303/322 (94.1) 2.3 (–1.6 to 6.2) 0.25 ▪ PP 302 /329 (91.8) 263 /267 (98.5) 6.7 (3.4 to 10.0) 0.001 BBPS score ≥ 2 in all segments, n/N (%) ▪ ITT 237/302 (78.5) 249/303 (82.2) 3.7 (–2.6 to 10.0) 0.25 ▪ PP 237/302 (78.5) 223/263 (84.8) 6.3 (0.0 to 12.7) 0.05 Right colon BBPS score ≥ 2, n/N (%) ▪ ITT 235/284 (82.7) 242/284 (85.2) 2.5 (–3.6 to 8.5) 0.42 ▪ PP 235/284 (82.7) 218/248 (87.9) 5.2 (–0.8 to 11.1) 0.10 Transverse colon BBPS score ≥ 2, n/N (%) ▪ ITT 255/290 (87.9) 269/291 (92.4) 4.5 (–0.3 to 9.3) 0.07 ▪ PP 255/290 (87.9) 235/253 (92.9) 5 (0.0 to 9.9) 0.05 Left colon BBPS score ≥ 2, n/N (%) ▪ ITT 259/301 (86.0) 274/303 (90.4) 4.4 (–0.7 to 9.5) 0.10 ▪ PP 259/301 (86.0) 242/263 (92.0) 6 (0.9 to 11.1) 0.03 Complete colonoscopy, n/N (%) ▪ ITT 265/302 (87.7) 280/303 (92.4) 4.7 (–0.1 to 9.4) 0.06 ▪ PP 265/302 (87.7) 244/263 (92.8) 5 (0.2 to 9.9) 0.046 Adherence to low-fiber diet, n/N (%) ▪ ITT 264/300 (88.0) 256/302 (84.8) –3.2 (–8.7 to 2.2) 0.25 ▪ PP 264/300 (88.0) 222/262 (84.7) –3.3 (–9.0 to 2.4) 0.26 Laxative intake > 75 %, n/N (%) ▪ ITT 294/301 (97.7) 296/300 (98.7) 1 (–1.1 to 3.1) 0.36 ▪ PP 294/301 (97.7) 256/260 (98.5) 0.8 (–1.5 to 3.1) 0.50 Interval*< 5 hours, n/N (%) ▪ ITT 232/277 (83.8) 238/276 (86.2) 2.5 (–3.5 to 8.4) 0.42 ▪ PP 232/277 (83.8) 206/237 (86.9) 3.2 (–2.9 to 9.3) 0.31 ARD, absolute risk difference; CI, confidence interval; ITT, intention-to-treat population; PP, per-protocol population; BBPS, Boston Bowel Preparation Score. * Interval refers to the interval between the start of the last laxative intake and the colonoscopy. vention (per-protocol analysis), bowel preparation success in- without differences between the two interventions. Unlike creased by 11.5 %. these two RCTs, it is important to note that the present study Two previous single-center RCTs investigated educational re- included only patients who had previous unsuccessful bowel inforcement by telephone. Liu et al. [11] demonstrated that tel- preparation, which has been identified as the most significant ephone re-education on the day before the colonoscopy in- factor predicting poor bowel preparation, making our patients creased the rate of adequate bowel preparation (70.3 % vs. a truly difficult-to-prepare population. This could also explain 81.6 %; P = 0.001). Another RCT showed that educational inter- the low telephone contact rate. In addition, our patients had vention by telephone or SMS prior to colonoscopy improved higher rates of nonmodifiable risk factors for poor bowel prepa- bowel preparation in both groups compared with controls [12], ration than the other studies, which included a nonselected Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). 1031 Original article ▶ Table 3 Detected lesions. such as split dosing, a short interval between the final laxative dose and the colonoscopy, and specific verbal and written in- Variable Control (n = 329) Telephone (n = 322) P value structions explaining the bowel preparation. We chose 4 L of PEG rather than low-volume PEG, following the evidence from Mean adenoma per patient (95 %CI) a recent RCT in patients with bowel preparation failure [19]. ▪ ITT 0.84 (0.66 to 1.03) 1.14 (0.89 to 1.4) 0.07 Furthermore, pump irrigation, which has been proven effective ▪ PP 0.84 (0.66 to 1.03) 1.1 (0.84 to 1.35) 0.11 for increasing bowel cleansing [25], was included for all pa- tients in the trial. Although other approaches may be consid- Overall adenoma detection rate, n/N (%) ered, such as additional laxative intake the same day or the ▪ ITT 117/302 (38.7) 130/303 (42.9) 0.30 next day following the examination, or the administration of ▪ PP 117/302(38.7) 116/263 (44.1) 0.20 enemas through the colonoscope, the implementation of these strategies in clinical practice is limited by scheduling problems. Proximal adenoma detection rate, n/N (%) Despite the heterogeneity of the interventions for reinfor- ▪ ITT 78/302 (25.8) 94/303 (31.0) 0.16 cing medical education before colonoscopy, in general they ▪ PP 78/302 (25.8) 85/263 (32.3) 0.09 have been shown to improve cleansing quality [26]. In our study, we applied our best knowledge to deliver instructions at Distal adenoma detection rate, n/N (%) the colonoscopy request time, such as a clearly written leaflet ▪ ITT 62/302 (20.5) 82/303 (27.1) 0.06 and a nurse-led face-to-face interview to individualize bowel ▪ PP 62/302 (20.5) 71/263 (27.0) 0.07 preparation. In addition, the telephone interview shortly before the colonoscopy appointment was conducted by an experi- Multiple adenoma (≥ 3), n/N (%) enced nurse because it allows direct bidirectional communica- ▪ ITT 29/302 (9.6) 45/303 (14.9) 0.049 tion that may increase the comprehension and adherence to in- ▪ PP 29/302 (9.6) 39/263 (14.8) 0.06 structions. The timing of the telephone call shortly before the colonoscopy appointment was chosen because laxative intake Overall serrated detection rate, n/N (%) and dosing are the most important factors affecting the quality ▪ ITT 27/302 (8.9) 45/303 (14.9) 0.03 of bowel preparation [27]. Telephone intervention planned well ▪ PP 27/302 (8.9) 40/263 (15.2) 0.02 in advance of the colonoscopy may have increased the adher- ence to the recommended diet. However, recent studies have Invasive neoplasia, n/N (%) shown that diet restrictions are not so important in increasing ▪ ITT 5/302 (1.7) 6/303 (2.0) 0.77 bowel preparation effectiveness [18, 28], and the reminder ▪ PP 5/302 (1.7) 5/263 (1.9) 0.83 about laxative intake may fade over time. A face-to-face visit to educate patients may be at least as ef- CI, confidence interval; ITT, intention-to-treat population; PP, per-protocol fective, if not better than a telephone call. However, visits re- population. quire more resources, are more rigid in terms of patient and nurse availability, and have more scheduling limitations. These issues would probably make a face-to-face intervention more population. Therefore, our intervention may be considered as a expensive and more difficult to implement than a telephone salvage strategy for difficult-to-prepare patients, and the ap- call. In our trial, an initial face-to-face visit was required in order parent negative results of the intervention could be under- to conduct the RCT. During this visit, the investigators educa- mined by the characteristics of the included sample [6]. ted patients regarding bowel preparation instructions. Such The abovementioned studies have several flaws. First, a education, given by experienced investigators, may have re- strikingly low rate of adequate bowel cleansing in both the con- duced the potential benefit of the telephone intervention. trol and intervention groups was found [11] compared with As expected, we found that the benefit of this telephone in- large prospective studies in unselected populations [24]. Sec- tervention was limited to those patients who could be contac- ond, regular instructions provided by a nurse and colonoscopy ted, with a positive effect on cleansing quality overall and per in such a short time frame raises concerns about the quality of segment; 17 % of the patients could not be contacted and thus the standard education [11]. Third, these studies were focused did not benefit. We did not find significant differences in the on patients at low risk of poor bowel preparation, such as a baseline characteristics between patients who were contacted screening population, which probably benefits less from this and those who were not. However, information about the so- type of intervention. Fourth, the studies lacked important in- cioeconomic status that may have influenced the applicability formation such as the nonattendance rate or the contact rate of the telephone intervention was not analyzed. for the telephone intervention. Finally, the results may not be The telephone intervention was particularly effective in pa- extrapolated to Western populations, and the single-center tients who were referred for symptoms, whereas there was no settings prevent external validation. significant benefit in screening or surveillance patients. It is well Inadequate bowel preparation is a major burden requiring known that the baseline bowel preparation success rate is higher innovative solutions. In our trial, we decided to include a num- in patients referred for screening colonoscopy, as these patients ber of measures that have proven efficacy in bowel cleansing, usually have fewer comorbid conditions. The past experience of 1032 Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). ▶ Table 4 Bowel preparation success by subgroups of risk factors. Variable Control, n/N (%) Telephone, n/N (%) ARD (95 %CI) LR* Corrected P value Diabetes mellitus 4.85 0.35 ▪ Yes 52/79 (65.8) 42/61 (68.9) 3 (–12.6 to 18.0) ▪ No 185/250 (74.0) 207/261 (79.3) 5.3 (–2.0 to 12.6) Abdominal/pelvic surgery 5.08 0.32 ▪ Yes 99/138 (71.7) 96/135 (71.1) –0.6 (–11.3 to 10.0) ▪ No 138/191 (72.3) 153/187 (81.8) 9.6 (1.1 to 17.9) Constipation 6.8 0.13 ▪ Yes 83/123 (67.5) 89/125 (71.2) 3.7 (–7.7 to 15.0) ▪ No 153/202 (75.7) 159/196 (81.1) 5.4 (–2.7 to 13.4) Indication 17.22 0.007 ▪ Screening 71/87 (81.6) 71/85 (83.5) 1.9 (–9.6 to 13.3) ▪ Surveillance 76/96 (79.2) 71/95 (74.7) –4.4 (–16.3 to 7.5) ▪ Symptoms 89/145 (61.4) 107/142 (75.4) 14 (3.2 to 24.3) ARD, absolute risk difference; CI, confidence interval; LR, likelihood ratio. * Chi-squared test. patients undergoing surveillance colonoscopy could also affect Our study has some limitations. First, the educational inter- their baseline adherence to bowel preparation instructions, vention only had a positive effect when patients were success- reducing the benefit of the telephone intervention [24]. fully contacted by telephone. However, this fact is also proof of In the present study, more patients with multiple adenomas the benefit of such an intervention. Second, to standardize the (≥ 3) and more serrated lesions were detected in the interven- intervention, we centralized all telephone calls at the coordi- tion group. These findings may be explained by the better bowel nating center in Barcelona. However, we believe that from a cleansing found in the per-protocol analysis in the transverse pragmatic point of view, this intervention should be performed and left colon segments and more complete colonoscopies in by local centers. In any case, it is interesting to note that this the telephone group. It is also worth mentioning that the lesions contact rate (83 %) was similar to another single-center study detected in the colonoscopy, including 11 cancers (1.7 %), had from our group [31]. Third, some secondary outcomes were been missed during the index colonoscopy. It is important to planned a priori but were not listed in the registered protocol note that poor bowel cleansing prevents both complete colo- at ClinicalTrials.gov. Fourth, bowel stenosis may have been con- noscopy and mucosal visualization in the explored colon. These sidered as an exclusion criterion as it may impair bowel cleans- results illustrate the importance of repeating colonoscopies in ing; however, only two colonoscopies were incomplete due to cases of inadequate cleansing [29]. malignant stenosis. Fifth, patients with colonoscopy appoint- Another aspect is that the cost-effectiveness analysis re- ment on Mondays were contacted on Fridays (72 hours before vealed that the nurse-led telephone education was cost-saving. the colonoscopy). This situation may have influenced the con- Our study has several strengths. First, it is the first RCT to tact rate. Sixth, the positive impact of our educational interven- evaluate an educational intervention in patients with a high tion was mainly because of the increase in the attendance rate risk of poor bowel preparation. Second, the multicenter design and not because of significantly better bowel cleansing. Al- favors the generalization of the results. Third, we used the though reminder tools could deliver similar benefits in the gen- BBPS, which is the most thoroughly validated scale for evaluat- eral population and be cost-effective [12], it is unclear whether ing the quality of bowel preparation, allowing comparisons be- the same effect is achieved in difficult-to-prepare patients. It tween studies. Fourth, we provided a telephone noncontact would be interesting to investigate whether the combination rate, which measured the applicability of the intervention. Fi- of a telephone call and an SMS as a backup contact method nally, to our knowledge, the best bowel cleansing recommen- would increase the attendance rate. Finally, we might also face dations (not including the telephone intervention material) a “ceiling effect” where reinforced education may not improve were provided to all included patients in the trial. This multifac- the bowel preparation efficacy over a threshold, particularly in torial approach has previously been shown to be beneficial [30]. patients with impaired bowel peristalsis. In that sense, we may consider that in patients with a past his- In conclusion, this multicenter trial showed that a nurse-led tory of poor bowel cleansing, it would be difficult to exceed the telephone educational intervention within 48 hours before colo- rate of 85 % successful cleansing. noscopy did not reach a significant increase in bowel preparation Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). 1033 Original article success in patients with previous failure. However, in the 83 % of [7] Ness RM, Manam R, Hoen H et al. Predictors of inadequate bowel preparation for colonoscopy. Am J Gastroenterol 2001; 96: 1797– patients who were contactable and received the intervention, 1802 the bowel preparation success rate was substantially improved. [8] Hassan C, East J, Radaelli F et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Acknowledgments update 2019. Endoscopy 2019; 45: 142–155 This paper was presented as an oral presentation at the endos- [9] Lebwohl B, Wang TC, Neugut AI. Socioeconomic and other predictors of colonoscopy preparation quality. Dig Dis Sci 2010; 55: 2014–2020 copy annual meeting of the Sociedad Española de Endoscopia [10] Jones RM, Woolf SH, Cunningham TD et al. The relative importance of Digestiva 2019, Alicante, Spain. It was also presented as an patient-reported barriers to colorectal cancer screening. Am J Prev oral presentation at the gastrointestinal annual meeting of the Med 2010; 38: 499–507 Asociación Española de Gastroenterología 2019, Madrid, Spain. [11] Liu X, Luo H, Zhang L et al. Telephone-based re-education on the day Finally, it was presented as a poster at United European Gastro- before colonoscopy improves the quality of bowel preparation and enterology Week (UEGW) 2019, Barcelona, Spain. the polyp detection rate: a prospective, colonoscopist-blinded, ran- This study was supported by grants from the Asociación Española domised, controlled study. Gut 2014; 63: 125–130 de Gastroenterología and the Societat Catalana de Digestología. [12] Lee YJ, Kim ES, Choi JH et al. Impact of reinforced education by tele- The authors gratefully acknowledge the valuable contributions phone and short message service on the quality of bowel preparation: a randomized controlled study. Endoscopy 2015; 47: 1018–1027 from all registered nurses who participated in the study: Rober- [13] Guo X, Yang Z, Zhao L et al. Enhanced instructions improve the quality to Borja Manzanares, Cristina Lao, Mariluz Mestre, and Montser- of bowel preparation for colonoscopy: a meta-analysis of randomized rat Cornet. In addition, we express our gratitude to Springer Na- controlled trials. Gastrointest Endosc 2017; 85: 90–97.e6 ture for editorial assistance. We also show our appreciation to [14] Johnson DA, Barkun AN, Cohen LB et al. Optimizing adequacy of both Lluis Mateu Castell and Marc Alegret Antonijuan for their bowel cleansing for colonoscopy: recommendations from the US collaboration in the study by collecting data. Finally, we thank Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol Francesc Cots Reguant for his help with the cost-effectiveness 2014; 109: 1528–1545 analysis. [15] Clark BT, Protiva P, Nagar A et al. Quantification of adequate bowel preparation for screening or surveillance colonoscopy in men. Gas- troenterology 2016; 150: 396–405 Competing interests [16] Dumonceau J-M, Riphaus A, Schreiber F et al. Non-anesthesiologist administration of propofol for gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy, European Society of Gastro- Marco Antonio Álvarez-Gonzáles has received honoria from Norgine enterology and Endoscopy Nurses and Associates Guideline – upda- Ldt. for advisory board attendance, speaking and teaching and from ted June 2015. Endoscopy 2015; 47: 1175–1189 Casen-Recordati for speaking and teaching. [17] Hassan C, Bretthauer M, Kaminski MF et al. Bowel preparation for co- lonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Clinical trial guideline. Endoscopy 2013; 45: 142–150 [18] Alvarez-Gonzalez MA, Pantaleon MA, Flores-Le RouxJA et al. Ran- domized clinical trial: a normocaloric low-fiber diet the day before Trial Registration: ClinicalTrials.gov | Registration number (trial ID): colonoscopy is the most effective approach to bowel preparation in NCT03055689 | Type of study: prospective, randomized, multi-cen- colorectal cancer screening colonoscopy. Dis Colon Rectum 2019; 62: ter study 491–497 [19] Gimeno-García AZ, Hernandez G, Aldea A et al. Comparison of two References intensive bowel cleansing regimens in patients with previous poor bowel preparation: a randomized controlled study. Am J Gastroenter- ol 2017; 112: 951–958 [1] Kaminski MF, Thomas-Gibson S, Bugajski M et al. Performance meas- [20] Calderwood AH, Jacobson BC. Comprehensive validation of the Bos- ures for lower gastrointestinal endoscopy: a European Society of ton Bowel Preparation Scale. Gastrointest Endosc 2010; 72: 686–692 Gastrointestinal Endoscopy (ESGE) quality improvement initiative. United Eur Gastroenterol J 2017; 5: 309–334 [21] Gimeno-García AZ, Baute JL, Hernandez G et al. Risk factors for in- adequate bowel preparation: a validated predictive score. Endoscopy [2] Mahmood S, Farooqui SM, Madhoun MF. Predictors of inadequate 2017; 49: 536–543 bowel preparation for colonoscopy: a systematic review and meta-a- nalysis. Eur J Gastroenterol Hepatol 2018; 30: 819–826 [22] Dik VK, Moons LMG, Hüyük M et al. Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bow- [3] Clark BT, Rustagi T, Laine L. What level of bowel prep quality requires el preparation: development and validation of a prediction score. early repeat colonoscopy: systematic review and meta-analysis of the Gastrointest Endosc 2015; 81: 665–672 impact of preparation quality on adenoma detection rate. Am J Gas- troenterol 2014; 109: 1714–1723 [23] Diari Oficial de la Generalitat de Catalunya ORDRE SLT/165/2018. contraprestació de l’atenció hospitalària i especialitzada; 2018: [4] Rex DK, Imperiale TF, Latinovich DR et al. Impact of bowel preparation Available from: https://portaldogc.gencat.cat/utilsEADOP/PDF/ on efficiency and cost of colonoscopy. Am J Gastroenterol 2002; 97: 7723/1697258.pdf 1–10 1696–1700 [24] Mangas-Sanjuan C, Santana E, Cubiella J et al. Variation in colonosco- [5] Saltzman JR, Cash BD, Pasha SF et al. Bowel preparation before colo- py performance measures according to procedure indication. Clin noscopy. Gastrointest Endosc 2015; 81: 781–794 Gastroenterol Hepatol 2020; 18: 1216–1223.e2 [6] Ben-Horin S, Bar-Meir S, Avidan B. The outcome of a second prepara- [25] Rigaux J, Juriens I, Devière J. A novel system for the improvement of tion for colonoscopy after preparation failure in the first procedure. colonic cleansing during colonoscopy. Endoscopy 2012; 44: 703–706 Gastrointest Endosc 2009; 69: 626–630 1034 Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). [26] Hernández G, Gimeno-García AZ, Quintero E. Estrategias para opti- [29] Chokshi RV, Hovis CE, Hollander T et al. Prevalence of missed adeno- mizar la calidad de la limpieza colónica. Gastroenterol Hepatol 2019; mas in patients with inadequate bowel preparation on screening co- 42: 326–338 lonoscopy. Gastrointest Endosc 2012; 75: 1197–1203 [27] Radaelli F, Paggi S, Hassan C et al. Split-dose preparation for colonos- [30] Alvarez-Gonzalez MA, Flores-Le Roux AA, Seoane A et al. Efficacy of a copy increases adenoma detection rate: a randomised controlled trial multifactorial strategy for bowel preparation in diabetic patients un- in an organised screening programme. Gut 2017; 66: 270–277 dergoing colonoscopy: a randomized trial. Endoscopy 2016; 48: [28] Gimeno-García AZ, de la Barreda Heuser R, Reygosa C et al. Impact of 1003–1009 a 1-day versus 3-day low-residue diet on bowel cleansing quality be- [31] Seoane Urgorri A, Font Lagarriga X, Pérez Berbegal R et al. Educational fore colonoscopy: a randomized controlled trial. Endoscopy 2019; 51: telephone intervention by endoscopy nurse. Impact on the adherence 628–636 of outpatient colonoscopy. Endoscopy 2019; 51: (Suppl. 04): S125 Alvarez-Gonzalez Marco Antonio et al. Telephone intervention to improve bowel preparation … Endoscopy 2020; 52: 1026–1035 | © 2020. The Author(s). 1035