Ischemic stroke J NeuroIntervent Surg: first published as 10.1136/neurintsurg-2018-014122 on 30 July 2018. Downloaded from http://jnis.bmj.com/ on April 23, 2021 by guest. Protected by copyright. Original research ADAPT technique with ACE68 and ACE64 reperfusion catheters in ischemic stroke treatment: results from the PROMISE study Peter Schramm,1 Pedro Navia,2 Rosario Papa,3 Joaquin Zamarro,4 Alejandro Tomasello,5,6 Werner Weber,7 Jens Fiehler,8 Patrik Michel,9 Vitor M Pereira,10 Timo Krings,11,12 Jan Gralla,13 Paola Santalucia,14 Laurent Pierot,15 T H Lo16 For numbered affiliations see Abstract endovascular therapy,8–10 a significant growth end of article. Background and purpose The recent randomized in the treatment of patients with emergent large trials demonstrated the benefit of mechanical vessel occlusion (ELVO) has been observed and is Correspondence to thrombectomy in stroke therapy. However, treatment expected to continue.11–13 An operational defini- Professor Peter Schramm, Department of Neuroradiology, using different strategies is an ongoing area of tion of ELVO to standardize the description of the University Medical Center investigation. The PROMISE study analyzed the safety therapeutic target for endovascular thrombectomy Schleswig-Holstein, Luebeck and effectiveness of the Penumbra System with the was proposed.14 Recently, several studies have 23538, Germany; ​Peter.​ ACE68 and ACE64 reperfusion catheters in aspiration investigated patient outcomes after advances in Schramm@u​ ksh.​de thrombectomy of stroke, using A Direct Aspiration First different devices and techniques, increased physi- Received 31 May 2018 Pass Technique (ADAPT). cian experience, and streamlined in-hospital proce- Revised 2 July 2018 Methods PROMISE was a prospective study which dures for endovascular therapy.15–18 The Penumbra Accepted 5 July 2018 enrolled 204 patients with intracranial anterior System (Penumbra, Inc., Alameda, CA) is a family Published Online First 30 July 2018 circulation large vessel occlusion (LVO) ischemic stroke of mechanical thrombectomy devices specifically in 20 centers from February 2016 to May 2017. Initial designed to remove thrombus through aspiration, treatment was with the ACE68/ACE64 catheters within receiving 510(k) clearance from the US FDA in 6 hours of symptom onset. Imaging and safety review 2007.19 20 THERAPY was an RCT assessing aspi- was performed by an independent Core Laboratory and ration thrombectomy with IV rt-PA versus IV rt-PA a Clinical Events Committee. The primary angiographic alone.21 Further developments included ADAPT (A outcome was revascularization to mTICI 2b-3 at Direct Aspiration First Pass Technique), a throm- immediate post-procedure and the primary clinical bectomy approach wherein aspiration alone is used outcome was 90-day modified Rankin Scale (mRS) score to remove the occlusion, followed by adjunctive ≤2. Safety assessment included device- and procedure- therapies if necessary.22–24 In addition, findings related serious adverse events (SAEs), symptomatic from the Penumbra 3D RCT, which randomized intracranial hemorrhage (sICH), mortality, and patients to either a frontline approach with the 3D embolization of new territory (ENT). stent retriever with aspiration vs aspiration alone, Results Enrolled patients had a median age of 74 (IQR demonstrated no significant difference between 65–80) years and a median admission NIHSS of 16 (IQR treatment groups in the rates of modified Throm- 11–20). The post-procedure mTICI 2b-3 revascularization bolysis in Cerebral Infarction (mTICI) 2–3 revas- rate was 93.1% and the 90-day mRS 0–2 rate was 61%. cularization, 90-day modified Rankin Scale (mRS) Device- and procedure-related SAEs at 24 hours occurred 0–2, symptomatic intracranial hemorrhage (sICH), in 1.5% and 3.4%, respectively, 90-day mortality was procedure or device-related serious adverse events 7.5%, sICH occurred in 2.9% while ENT occurred in (SAEs), or mortality.25 1.5%. At the time of this study’s design, the safety and Conclusions For frontline therapy of LVO stroke, the efficacy of the ADAPT technique using ACE68/64 ACE68/ACE64 catheters for aspiration thrombectomy catheters with the Penumbra System (PS) had not were found to be safe and showed similar efficacy been assessed in a prospective study. The aim of a to randomized trials using other revascularization prospective, multicenter, observational, single-arm techniques. European Registry on the ACE reperfusion cath- Clinical Trial Registration : NCT02678169;Pre- eters and the Penumbra System in the treatment results. of acute ischemic stroke (PROMISE) study was © Author(s) (or their to address this need for real-world data on the employer(s)) 2019. Re-use permitted under CC BY-NC. No safety and effectiveness of the PS with the novel commercial re-use. See rights Penumbra reperfusion catheters, ACE68/64, in and permissions. Published Introduction patients with AIS from anterior circulation LVO, by BMJ. Six randomized controlled trials (RCTs) estab- treated with the ADAPT technique. The PROMISE To cite: Schramm P, Navia P, lished the role of mechanical thrombectomy in study incorporated an integrated aspiration throm- Papa R, et al. early acute ischemic stroke (AIS):1–6 in these trials, bectomy system which includes a Penumbra aspi- J NeuroIntervent Surg most of the devices used were stent retrievers.7 ration pump indicated for revascularization of AIS 2019;11:226–231. As a result of position statements recommending patients. 226   Schramm P, et al. J NeuroIntervent Surg 2019;11:226–231. doi:10.1136/neurintsurg-2018-014122 Ischemic stroke J NeuroIntervent Surg: first published as 10.1136/neurintsurg-2018-014122 on 30 July 2018. Downloaded from http://jnis.bmj.com/ on April 23, 2021 by guest. Protected by copyright. Methods European investigational sites, and an exclusion log of screened PROMISE was a prospective, multicenter, single-arm, open-label, but not enrolled patients was kept at each site. observational European study to evaluate the safety and effec- tiveness of the ACE68/64 reperfusion catheters and the PS in the Primary and secondary endpoints treatment of AIS (​ClinicalTrials.​gov Identifier, NCT02678169). Primary endpoints were angiographic revascularization assessed Patients presenting within 6 hours from symptom onset with an by digital subtraction angiography of the occluded target anterior circulation LVO AIS (within the internal carotid artery vessel to mTICI 2b or 3 at immediate post-procedure as adju- (ICA) and internal carotid terminus, middle cerebral artery dicated by an independent Core Laboratory and functional (MCA) – M1/M2 segments) were eligible. This study was a independence (mRS 0–2) at 90 days by mRS certified medical non-inferiority comparison of 90-day mRS 0–2 rates between personnel, without blinding to the clinical or radiological patient the ACE Penumbra System group and the intra-arterial therapy data. Secondary endpoints were any device- and procedure-re- (IAT) group in the MR CLEAN trial.1 At the time of study design, lated SAEs at 24 hours' and 30 days' post-procedure, all-cause MR CLEAN established the benefit of intra-arterial therapy morbidity (defined as mRS 3–5) and mortality at 90 days, occur- against medical management alone and was the only published rence of ENT, occurrence of sICH at 24 hours, and occurrence RCT for our non-inferiority hypothesis and sample size calcula- of vessel damage at the end of the ADAPT procedure. Safety tion. The main aim of the study, however, was to assess the safety was assessed by collecting adverse events data during all study and effectiveness of the ACE68/64 in patients treated with the visits. Hemorrhagic transformation was radiologically clas- ADAPT technique. Every patient was checked for study eligi- sified according to the European Cooperative Acute Stroke bility and recorded on a site-specific Screening Log. Study (ECASS) definitions. sICH was defined according to Treatment consisted of the ADAPT technique with thrombo-as- ECASS-II definition26 27 as a four point or greater deterioration piration using ACE68 and ACE64 as first intention according to in the NIHSS within 24 hours after treatment compared with site routine practice. For rescue, any approved revascularization the pre-procedure NIHSS attributable to imaging evidence of device and/or intra-arterial medication was allowed at the oper- an intracranial hemorrhage as adjudicated by the Core Imaging ators’ discretion, including non-Penumbra devices. Adjunctive Laboratory. Safety endpoints were adjudicated for severity and therapy was defined as the use of a stent retriever following a causality by an independent Clinical Events Committee (CEC). reperfusion catheter: before adjunctive therapy, three passes of All data were monitored during on-site visits. the ACE catheter were recommended. At the discretion of the Secondary efficacy endpoints included good functional neuro- clinicians in charge of the patient or the investigator, the patient logical recovery defined as a reduction of 10 or more points in was pretreated with intravenous thrombolytics (IV tPA), and/or the NIHSS or a score of 0–1 at 7 to 10 days' post-procedure, treated under general or local anesthesia, or conscious sedation. times to mTICI ≥2 b revascularization, health economics data, Follow-up visits to assess functional outcome, quality of life, and and Quality of Life as assessed by EQ-5D-3L score at 90 days adverse events took place at 24 hours, 7 to 10 days or discharge, compared with 7 to 10 days. 30-days, and 90-days post-procedure. In Europe, the ACE68 and ACE64 catheters were available in 2016 and 2015, respectively. Statistical analysis All procedures were in accordance with national and local Baseline clinical and imaging data were summarized using ethical and institutional guidelines and site routine clinical standard descriptive statistics. This included the number of practice. The local Ethics Committees approved the study, and observations, mean, median, SD, minimum and maximum for the patients or their representatives provided written informed continuous variables, and counts and percentages for discrete consent, according to local regulations. variables. All confidence intervals presented were two-sided. All statistical tests were two-tailed with a significance level of 0.05. Imaging analysis Analyses were performed using SAS software (version 9.4; SAS All imaging scans (baseline CT/MRI, pre-procedure/procedure Institute).28 DSA, and 24 hours' scan) were reviewed and adjudicated by The primary effectiveness analysis was an unadjusted non-in- an independent Core Imaging Laboratory (Toronto Western feriority comparison between the ACE68/64 reperfusion cath- Hospital, University of Toronto) for mTICI and for procedural eters Penumbra System group and the IAT group from the MR and safety assessments (confirmation of vessel damage and CLEAN trial. For sample size calculation, it was assumed that embolization of new territory (ENT), identification, and classifi- 38% (76/200) of the PS patients would experience primary cation of intracranial hemorrhages). endpoint success for 90-day mRS 0–2 compared with 32.6% (76/233) of the MR CLEAN IAT group: the estimated difference and 95% CI for the difference between groups would therefore Patients be 5.4% (-3.7%, 14.4%). As the primary analysis, all efficacy and Patient eligibility criteria included age of at least 18 years, safety outcome measures were analyzed under the intent-to-treat presentation with anterior circulation LVO within 6 hours of (ITT) principle. stroke onset or time last known to be well, occlusion of the Prespecified analyses of association between primary and internal carotid artery (ICA and ICA terminus) or MCA M1/ selected secondary endpoints (mTICI 2b-3 post-procedure, M2, National Institutes of Health Stroke Scale (NIHSS)≥2, and 90-day mRS 0–2, device- or procedure-related SAEs at 24 hours pre-stroke mRS score ≤2. LVO status was determined mostly and 30 days, 90-day mortality, occurrence of sICH) were by CTA (85.3%), with some by MRA (14.7%). Imaging eligi- conducted, with adjustment for several baseline characteristics bility criteria were CT Alberta Stroke Program Early CT Score (age, baseline NIHSS, occlusion location). (ASPECTS)≥6 or MR DWI ASPECTS≥5, and absence of tandem extracranial occlusion or severe arterial stenosis requiring Results treatment prior to thrombectomy. Study exclusion criteria can Baseline patient data be found in the Online Supplement. Up to 210 patients who Between February 2016 and May 2017, the PROMISE study met eligibility criteria were to be enrolled in a maximum of 25 enrolled 204 patients across 20 European centers using ADAPT Schramm P, et al. J NeuroIntervent Surg 2019;11:226–231. doi:10.1136/neurintsurg-2018-014122 227 Ischemic stroke J NeuroIntervent Surg: first published as 10.1136/neurintsurg-2018-014122 on 30 July 2018. Downloaded from http://jnis.bmj.com/ on April 23, 2021 by guest. Protected by copyright. with the Penumbra System and ACE68/64 catheters as frontline Table 1 Baseline and procedural characteristics treatment. For enrollment, 30 (14.7%) patients were selected by MRI and 174 (85.3%) by CT. Of the 1433 patients screened Characteristic Patients (N) and documented in site-specific Screening and Enrollment Logs, Age, years 71.3±12.4 (204) (mean±SD) 1229 patients (85.8%) were screen failures and 204 patients 74/65–80 (median/IQR) (14.2%) were enrolled. The five most common reasons for Female 61.8% (126/204) screen failure were no imaging evidence of LVO of the ante- Baseline NIHSS 15.4±5.8 (204) (mean±SD) rior circulation (22.1%, 271/1229), followed by unknown onset 16/11–20 (median/IQR) of stroke symptoms with last proof of good health more than  < 16 46.6 % (95/204) 6 hours before (10.3%, 126/1229), lack of possibility to obtain informed consent (10.2%, 125/1229), onset of stroke symp-  16 – 20 32.8 % (67/204) toms >6 hours (8.2%, 101/1229) or angiographic evidence of  > 20 20.6 % (42/204) tandem extracranial occlusion or arterial stenosis proximal to CT ASPECTS*: per site assessment 8.7±1.2 (173) (mean±SD) occlusion requiring treatment prior to thrombus removal (8.2%, 9/8–10 (median/IQR) 101/1229). Four patients withdrew consent prior to the 90-day MR DWI ASPECTS: per site assessment 7.4±1.5 (30) (mean±SD) visit, therefore, 200 patients completed the 90-day visit and 8/6–8 (median/IQR) were included in the follow-up analysis. IV rt-PA administered prior to procedure 61.8% (126/204) Baseline characteristics are displayed in table 1. The median Time from symptom onset to hospital admission 115.3±78.6 (204) (mean±SD) age was 74 years, ranging from 27 to 96 years, and almost (min) 97.0/58.5–154.5 (median/IQR) two-thirds of the patients were women (61.8%). Thirty-five percent (35.3%) of patients were transferred from other hospi- Site of vessel occlusion tals, 79.9% of stroke onsets were witnessed, and 20.1% of Internal carotid artery/carotid T 21.1% (43/204) patients were last known to be well within 6 hours before inclu- Middle cerebral artery 78.9 % (161/204) sion without knowing the exact time of onset. The median time First segment (M1) 60.8% (124/204) from stroke onset to hospital admission was 97 min (IQR 58.5– 154.5). The median baseline NIHSS score was 16 (IQR 11–20) Second segment (M2) 18.1% (37/204) and ranged from 2 to 36. At admission, the median CT ASPECTS Procedural information was 9, while the median MRI DWI ASPECTS was 8. Occlusions Penumbra ACE Catheters, (% n/N) All patients (n=204) were located in the ICA/carotid T (21.1%) and MCA (78.9%; Frontline device 60.8% in M1, 18.1% in M2) and IV rt-PA was administered in  ACE68 65.7 % (134/204) 126 patients (61.8%), mainly within a bridging protocol 86.5% (109/126). At baseline, mTICI was 0 in most patients (91.2%,  ACE64 32.8 % (67/204) 186/204) with mTICI 1 in 8.3% (17/204) of patients. Other Penumbra catheters: 3MAX, 5MAX, ACE 60 1.5% (3/204)† The ACE68 catheter was utilized as frontline treatment in Frontline ACE68/64 catheter passes 1.6±0.9 (201) (mean±SD (N)) 65.7% of patients and the ACE64 in 32.8%: three patients 1/1–2 (median/IQR) (1.5%) were initially treated with other PS devices (table 1). For Additional mechanical intervention (% n/N)‡ ACE 68/64 PATIENTS n=201 cases that required adjunctive therapy, the median number of ACE68/64 passes performed before switching was 2 (IQR 1–3). Stent retriever after Penumbra System, total 20.9 % (42/201) General anesthesia was performed in 58.3%, conscious sedation  Target vessel/remaining clot 13.4 % (27/201) in 18.1%, and local anesthesia only in 23.5% of patients. A stent  Distal vasculature 9% (18/201) was placed for proximal stenosis or dissection in 2% of patients, Stent for proximal stenosis or dissection 2% (4/201) and balloon angioplasty was used for proximal stenosis in 2% of Balloon angioplasty for proximal stenosis 2% (4/201) patients. In 20.9% of patients, a stent retriever was used after PS as adjunctive treatment, in 13.4% of cases at the target vessel, Catheter from other manufacturer 1% (2/201) 9% in distal vasculature, and 1.5% in both. No balloon guide Data are % (n/N) or mean ±SD (N) (median) (IQR). ASPECTS, Alberta Stroke Program catheters were reported to be used. Early CT Score; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale. *One patient with ASPECTS score not available due to a previous stroke. Principal Primary outcomes Investigator confirmed the inclusion of the patient. The proportion of patients with Core Laboratory-assessed †Three patients were treated with ACE60, 3MAX, or 5MAX, admitted under protocol mTICI 2b-3 was 93.1% (190/204) after all treatment (39.2% version B. mTICI 3, 53.9% mTICI 2b). After Penumbra System treatment ‡Patients may have more than one additional mechanical intervention. alone, 70.6% (144/204) of patients achieved mTICI 2b-3. Out of all patients achieving mTICI 2b-3 after ACE68/64, 74.4% and the remaining 10 patients died due to different causes (cere- (90/121) achieved revascularization after the first ACE68/64 bral hemorrhage, hemorrhagic transformation stroke, ischemic pass. At 90 days, 61% of patients (122/200) achieved good func- stroke, seven others not related to stroke). The ENT rate was tional outcome (mRS 0–2) (table 2). The study met its primary 1.5% (3/204), vessel perforation rate was 0.5% (1/204), distal effectiveness endpoint (Online Supplement). emboli rate was 1.0% (2/204), and vessel dissection rate was 2.5% (5/204) (table 2). The frequency of new ischemic stroke Secondary outcomes within 24 hours was 0%. Regarding safety endpoints, the all-cause mortality and morbidity Per adjudication by the CEC, there were nine device- and rates at 90 days were 7.5% (15/200) and 31.5% (63/200), respec- procedure-related SAEs (4.4%) at 30 days, of which seven (3.4%) tively, and the 24-hours sICH rate was 2.9% (6/204). According occurred within 24 hours. These events included carotid artery to MedDRA preferred terms, three patients died due to progres- dissection (n=2), cerebral artery embolism (n=2), cerebral sion of stroke, two patients died due to cerebrovascular accident, artery occlusion (n=1), cerebral hematoma (n=1), hemorrhagic 228 Schramm P, et al. J NeuroIntervent Surg 2019;11:226–231. doi:10.1136/neurintsurg-2018-014122 Ischemic stroke J NeuroIntervent Surg: first published as 10.1136/neurintsurg-2018-014122 on 30 July 2018. Downloaded from http://jnis.bmj.com/ on April 23, 2021 by guest. Protected by copyright. Table 2 Primary and secondary endpoints Outcome % (n/N) Primary endpoints mTICI 2b-3 at post-procedure: per core 93.1% (190/204) laboratory* mRS 0–2 at 90 days† 61% (122/200) Secondary endpoints Neurologic improvement‡ 67.9% (127/187) Device-related SAEs at 24 hours: per CEC 1.5% (3/204) Device-related SAEs at 30 days: per CEC 2.0% (4/204) Procedure-related SAEs at 24 hours: per CEC 3.4% (7/204) Procedure-related SAEs at 30 days: per CEC 4.4% (9/204) All-cause mortality at 90 days§ 7.5% (15/200) Morbidity at 90 days|| 31.5% (63/200) Symptomatic intracranial hemorrhage at 2.9% (6/204) 24 hours: per CEC# Embolization of new territory: per CEC 1.5% (3/204) Vessel damage: per CEC 2.9 % (6/204)  Vessel perforation 0.5 % (1/204)  Vessel dissection 2.5% (5/204) Symptom onset to ASPECTS CT/MRI, minutes 137.9±71.0 (204) (mean±SD) 127.5/81.5–188.0 (median/IQR) Imaging to arterial puncture, minutes 72.2±44.2 (204) (mean±SD) 61.5/41.0–91.5 (median/IQR) Arterial puncture to revascularization, minutes 40.1±27.2 (204) (mean±SD) 31.0/20.0–53.0 (median/IQR) EQ-5D-3L VAS improvement at 90 days 4.7±20.4 (119) (mean±SD) compared with 7–10 days 5/0–15 (median/IQR) Data are % (n/N) or mean ±SD (N) (median) (IQR). ASPECTS, Alberta Stroke Program Early CT Score; CEC, Clinical Events Committee; CI, confidence interval; IQR, interquartile range; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; SAE, serious adverse event. *For two patients missing Core Laboratory DSA review due to vessel not visualized, PI assessment of mTICI score carried over. †Four patients withdrew prior to the 90-day follow-up and were excluded from 90-day mRS analysis. ‡Good functional neurological recovery defined as a reduction of 10 or more points in the median NIHSS or a score of 0–1 at 7–10 days. Seventeen patients did not have 7–10 day NIHSS assessment. §Mortality assigned as 90-day mRS 6. ¶Morbidity defined as 90-day mRS 3–5. **Defined as 24 hours CT evidence of an ECASS-defined intracranial hemorrhage associated with a 4-point or more worsening of the NIHSS score. cerebral infarction (n=1), subarachnoid hemorrhage (n=1), Figure 1 Comparison of PROMISE time metrics with MR CLEAN, and vascular pseudoaneurysm (n=1). Regarding vessel damage STRATIS, and ASTER trials (A) MR CLEAN and PROMISE procedural time events (serious and non-serious), there were five arterial dissec- comparison. (B) STRATIS and PROMISE procedural time comparison. (C) tions, all of which were extracranial, and one perforation during ASTER and PROMISE procedural time comparison. stent retriever use in distal vasculature. Four of the five dissec- tions were unrelated to ACE catheter use and possibly/probably/ definitely related to the procedure. details of safety events, primary effectiveness analysis, and addi- Regarding secondary efficacy endpoints, good functional tional process times. neurological recovery was achieved in 67.9% of patients Self-reported assessment on quality of life at 90 days compared (127/187), with 35.3% (66/187) having NIHSS 0–1. The times with 7 to 10 days included improvement in mobility (9.9%), to revascularization endpoint data are shown in table 2. The self-care (14.5%), usual activities (19.0%), and pain/discomfort median reperfusion time (arterial access to mTICI 2b-3 or final (7.1%), and worsening in anxiety/depression (4.2%). Median angiogram if 2b-3 was not achieved) was 31 min (IQR 20–53), duration of index hospitalization was 8 days (IQR 5–11), which and the median time from stroke onset to mTICI 2b-3 or final is typical per European standard of care, and all-cause rehospi- angiogram was 245.5 min (IQR 192–305). The current time talization rate from discharge to 90 days was 8.3% (17/204). Of metrics are shown in figure 1. Please see Online Supplement for note, 73.5% of patients (150/204) were back home by 90 days. Schramm P, et al. J NeuroIntervent Surg 2019;11:226–231. doi:10.1136/neurintsurg-2018-014122 229 Ischemic stroke J NeuroIntervent Surg: first published as 10.1136/neurintsurg-2018-014122 on 30 July 2018. Downloaded from http://jnis.bmj.com/ on April 23, 2021 by guest. Protected by copyright. Subgroup analyses guidelines8–10 as seen in the rapid symptom onset to arterial In pre-specified subgroup analyses of primary and selected puncture time (comparison with MR CLEAN, STRATIS, and secondary endpoints, several baseline covariates were examined ASTER in figure 1) might also be correlated with better patient including stroke severity per NIHSS (<16, 16–20, or >20), age outcomes observed in PROMISE. These observations suggest (<80 or≥80 years), and occlusion location. In unadjusted anal- that the ADAPT technique is an effective method, and that the ysis, lower baseline NIHSS and younger age (<80 years) were rate of complications, especially of sICH, is low. This favorable predictors of functional independence. In addition, younger age safety profile may arise from the use of the recently introduced (<80 years) was a predictor of decreased mortality. No impact of large-bore catheters with improved trackability, resulting in less higher baseline NIHSS on the occurrence of sICH or mortality manipulation with multiple devices. Though not a prespecified was observed. In analysis adjusted for the significant predictors analysis, no significant differences in safety or effectiveness of baseline or outcome differences, there were no differences outcomes were noted between the two catheter groups, ACE64 in rates of 90-day mRS 0–2, mTICI 2b-3, or mortality between or ACE68. There were no differences in baseline patient char- transfer and direct-admit patients. For subgroup analysis details, acteristics, except for more cardiac heart failure, less peripheral please see Online Supplement. artery disease, and higher pre-stroke mRS >0, in the ACE68 group. The first-pass success rate with ADAPT was 60.2%, Discussion with no significant difference between catheter sizes (58.2% vs Results from the PROMISE study supported the safety and effec- 61.2%, ACE64 vs ACE68). Outcomes should be evaluated with tiveness of the ACE68 and ACE64 reperfusion catheters with caution due to the unknown impact of the baseline covariates. the PS in patients with AIS secondary to anterior LVO, using The potential impact of catheter size remains to be elucidated the ADAPT technique as frontline therapy in real-world prac- in a larger study with a matched patient population. In the tice. mTICI 2b-3 post-procedure was achieved in 93.1% of cases PROMISE study, balloon guide catheters were not used due to (including 20.9% of patients who were also treated with stent-re- lesional aspiration at the proximal face of the clot. trievers), and 61% of cases achieved 90-day mRS 0–2. The The primary limitation of the PROMISE study was inherent median time from arterial puncture to mTICI 2b-3 was 31  min. in its study design and lack of a randomized controlled compar- The safety profile was favorable with 7.5% early mortality, 2.9% ison, and the absence of blinding of the 3- month mRS assess- sICH, and 1.5% ENT rates. ment. Although PROMISE study criteria excluded patients In the ASTER RCT which randomly assigned patients to a with tandem lesions requiring treatment prior to aspiration, frontline approach with contact aspiration or stent retriever, nine patients (4.4%) with proximal stenosis were enrolled and therapy with the ADAPT technique was not superior to five required intervention (two stenting and angioplasty, one stent retrievers in safety or efficacy.16 A recent meta-analysis stenting, and two angioplasty alone), which may be a lower (HERMES) pooled patient-level data from five RCTs comparing proportion compared with other studies. The major strengths endovascular thrombectomy to standard medical care in patients of this study include evaluation by an independent Core Labora- with AIS. It showed the benefit of mechanical thrombectomy tory and a Clinical Events Committee, prospective and consecu- devices over medical management alone.7 The STRATIS study tive enrollment of patients to minimize potential bias associated determined that outcomes observed in a meta-analysis (SEER with a registry, all data being monitored during on-site visits, and Collaboration) pooling patient-level data from four RCTs could data collected from real-world clinical practice across Europe. be reproduced in a large real-world cohort.15 Data from the current study were compared with published Summary literature. Compared with ASTER, mTICI 2b-3 was achieved in As technical and clinical developments in stroke treatment evolve, 93.1% of patients in PROMISE (20.9% stent retriever use) vs these results suggest that in current practice, the ADAPT tech- 85.4% in ASTER (32.8% stent retriever use). Compared with nique with ACE68/ACE64 offers equal or better results compared the endovascular treatment groups in HERMES, STRATIS, and with other techniques. The findings from the PROMISE study ASTER, the proportion of patients with 90-day mRS scores 0–2 support the use of aspiration with ACE68/ACE64 reperfusion was higher in PROMISE (61% vs 46% in HERMES, 56.5% in catheters as a frontline therapy in the treatment of patients with STRATIS, and 45.3% in ASTER aspiration). Age and baseline ischemic stroke from large vessel occlusion. NIHSS in these trials were comparable to the PROMISE popu- lation, although other characteristics, such as tandem occlusion, Author affiliations 1 may vary. The 90-day mortality rate was satisfactory in PROMISE Department of Neuroradiology, University Medical Center Schleswig-Holstein, Luebeck, Germany (7.5% vs 15.3% in HERMES, 14.4% in STRATIS, 19.3% in 2 Radiology-Interventional Neuroradiology, Hospital Universitario Donostia, San ASTER aspiration). The rate of sICH in PROMISE was lower Sebastian, Spain 3 than HERMES and ASTER and higher than STRATIS (2.9% vs Radiology, Universita degli Studi di Messina, Messina, Italy 4 4.4% in HERMES, 1.4% in STRATIS, 5.3% in ASTER aspira- Interventional Neuroradiology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain tion). The rate of ENT observed in PROMISE was lower than 5 Department of Radiology, Section of Interventional Neuroradiology, Barcelona, ASTER and higher than STRATIS (1.5% vs 0.8% in STRATIS, Spain 3.7% in ASTER aspiration). It should be noted that ASTER used 6 Vall d’Hebron Research Institute (VHIR), Barcelona, Spain 7 almost exclusively ACE64 and 5MAX catheters over ACE68 (65 Radiology and Neuroradiology, Ruhr-University Bochum, University Medical Center ACE64, 1 ACE68, 63 5MAX devices were used frontline in the Langendreer, Bochum, Germany 8 Department of Neuroradiology, University Medical Center Hamburg Eppendorf, aspiration group). Hamburg, Germany The improvement in revascularization rates observed in 9 University of Lausanne, Lausanne, Switzerland 10 PROMISE might be due to the introduction of the ACE68/64 Medical Imaging, Toronto Western Hospital, Toronto, Ontario, Canada 11 catheters, along with improved technical skills due to the Division of Neuroradiology, Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada higher volume of endovascular treatment in recent years. On 12 Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, the other hand, improvements of in-hospital processing times University Health Network, Toronto, Ontario, Canada implemented after the introduction of new stroke treatment 13 Department for Diagnostic and Interventional Neuroradiology, Inselspital, University 230 Schramm P, et al. J NeuroIntervent Surg 2019;11:226–231. doi:10.1136/neurintsurg-2018-014122 Ischemic stroke J NeuroIntervent Surg: first published as 10.1136/neurintsurg-2018-014122 on 30 July 2018. Downloaded from http://jnis.bmj.com/ on April 23, 2021 by guest. Protected by copyright. of Bern, Bern, Switzerland 8 Mocco J, Fiorella D, Fargen KM, et al. Endovascular therapy for acute ischemic 14 IRCCS Centro Neurolesi Bonino Pulejo, Piemonte Hospital, Messina, Italy stroke is indicated and evidence based: a position statement. J Neurointerv Surg 15 Radiology, University Hospital Reims, Reims, France 2015;7:79–81. 16 Department of Interventional Radiology and Interventional Neuroradiology, 9 Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands Stroke Association Focused update of the 2013 guidelines for the arly management of patients with acute ischemic stroke regarding endovascular treatment: guideline Contributors All authors made a substantial, direct, and intellectual contribution for healthcare professionals rom the American Heart Association/American Stroke to the work. Association. Stroke 2015;46:3020–35. 10 Wahlgren N, Moreira T, Michel P, et al. Mechanical thrombectomy in acute ischemic Funding This study was funded by Penumbra, Inc (9508). stroke: consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported Competing interests The following investigators report financial conflicts with by ESO, ESMINT, ESNR and EAN. Int J Stroke 2016;11:134–47. this study: PS reports being a consultant for Penumbra and Stryker, and receiving 11 Hirsch JA, Yoo AJ, Nogueira RG, et al. Case volumes of intra-arterial and intravenous research support from Penumbra, Philips, and Siemens. RP reports proctoring treatment of ischemic stroke in the USA. J Neurointerv Surg 2009;1:27–31. and consulting for Medtronic, Penumbra, and Implemed. WW reports a proctor 12 Rai AT, Seldon AE, Boo S, et al. A population-based incidence of acute large vessel agreement with Microvention/Terumo, Medtronic, and Phenox, and being a occlusions and thrombectomy eligible patients indicates significant potential consultant with Penumbra (speaker and chairman fees). JF reports being a consultant for growth of endovascular stroke therapy in the USA. J Neurointerv Surg for Penumbra, Acandis, Boehringer Ingelheim, Cerenovus, Covidien, Medtronic, 2017;9:722–6. Microvention, Route92, and Stryker, and receiving research support from the 13 Williams MM, Wilson TA, Leslie-Mazwi T, et al. The burden of neurothrombectomy German Ministry of Science and Education (BMBF), German Ministry of Economy call: a multicenter prospective study. J Neurointerv Surg 2018. doi: 10.1136/ and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), neurintsurg-2018-013772. [Epub ahead of print 20 Apr 2018]. Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Philips, 14 Leslie-Mazwi T, Chandra RV, Baxter BW, et al. ELVO: an operational definition. J and Stryker. PM reports speaker and consulting fees from Medtronic, used for stroke Neurointerv Surg 2018;10:507–9. education. TK and VMP received funding from the sponsor for imaging core lab 15 Mueller-Kronast NH, Zaidat OO, Froehler MT, et al. Systematic evaluation of patients oratory activities. VMP reports being a consultant for Penumbra (PROMISE study), treated with neurothrombectomy devices for acute ischemic stroke: primary results of Medtronic, Stryker, and Neurovasc. LP received funding from Penumbra for CEC the Stratis Registry. Stroke 2017;48:2760–8. activities and is a consultant for Balt, Cerenovus/Neuravi, and Microvention. 16 Lapergue B, Blanc R, Gory B, et al. Effect of endovascular contact aspiration vs stent retriever on revascularization in patients with acute ischemic stroke and large vessel Patient consent Not required. occlusion: the Aster randomized clinical trial. JAMA 2017;318:443–52. Ethics approval The local Ethics Committees approved the study, and the patients 17 Frei D, McGraw C, McCarthy K, et al. A standardized neurointerventional or their representatives provided written informed consent, according to local thrombectomy protocol leads to faster recanalization times. J Neurointerv Surg regulations. 2017;9:1035–40. 18 Menon BK, Sajobi TT, Zhang Y, et al. Analysis of workflow and time to treatment Provenance and peer review Not commissioned; externally peer reviewed. on thrombectomy outcome in the Endovascular Treatment for Small Core and Data sharing statement Because of the sensitive nature of the data collected Proximal Occlusion Ischemic Stroke (ESCAPE) randomized, controlled trial. Circulation for this study, requests to access the dataset from qualified researchers trained in 2016;133:2279–86. human subject confidentiality protocols may be sent to Penumbra, Inc. at ​promise@​ 19 Penumbra Pivotal Stroke Trial Investigators. The Penumbra pivotal stroke trial: safety penumbrainc.c​ om. and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke 2009;40:2761–8. Open access This is an open access article distributed in accordance with the 20 Tarr R, Hsu D, Kulcsar Z, et al. The POST trial: initial post-market experience of the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke permits others to distribute, remix, adapt, build upon this work non-commercially, in the United States and Europe. J Neurointerv Surg 2010;2:341–4. and license their derivative works on different terms, provided the original work is 21 Mocco J, Zaidat OO, von Kummer R, et al. Aspiration thrombectomy after intravenous properly cited, appropriate credit is given, any changes made indicated, and the use alteplase versus intravenous alteplase alone. Stroke 2016;47:2331–8. is non-commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. 22 Kowoll A, Weber A, Mpotsaris A, et al. Direct aspiration first pass technique for the treatment of acute ischemic stroke: initial experience at a European stroke center. J References Neurointerv Surg 2016;8:230–4. 1 Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial 23 Lapergue B, Blanc R, Guedin P, et al. A Direct Aspiration, First Pass Technique (ADAPT) treatment for acute ischemic stroke. 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