Ethical Justification for Deferral of Consent in the AcT Trial for Acute Ischemic Stroke

Faris, Hannah; Dewar, Brian; Dowlatshahi, Dar; Ramji, Alnar; Kenney, Carol; Page, Stacey; Buck, Brian; Hill, Michael D.; Coutts, Shelagh B.; Almekhlafi, Mohammed; Sajobi, Tolulope T.; Singh, Nishita; Sehgal, Arshia; Swartz, Richard H.; Menon, Bijoy K; Shamy, Michel

doi:10.1161/strokeaha.122.038760

Cited by 8 publications

(10 citation statements)

References 22 publications

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“…The trial was regulated by Health Canada and approved by research ethics boards at each participating center. The trial used deferred consent procedures wherever approved by local research ethics boards . The study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.…”

Section: Methodsmentioning

confidence: 99%

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Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke

et al. 2023

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ImportanceIt is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke.ObjectiveTo examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke.Design, Setting, and ParticipantsThis was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent.ExposuresIntravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg).Main Outcomes and MeasuresThe primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out.ResultsAmong 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy.Conclusions and RelevanceThe findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

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Section: Methodsmentioning

confidence: 99%

“…The trial used deferred consent procedures wherever approved by local research ethics boards. 16 The study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.…”

Section: Study Populationmentioning

confidence: 99%

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke

et al. 2023

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“…This would ensure transparency and allow for peer review. (36) The use of deferral of consent should be assessed within an ethical framework like the substitute consent model proposed by Largent et al, (18) or the model we have proposed (39).…”

Section: How To Apply Deferral Of Consent: a 6 Step Operationalized A...mentioning

confidence: 99%

“…36 The use of deferral of consent should be assessed within an ethical framework such as the substitute consent model proposed by Largent et al 18 or the model we have proposed. 39 Step 4: Support physician-patient communication with scripts and other aids, and with training in how to use them.…”

Section: Independent Oversightmentioning

confidence: 99%

Protocol for Deferral of Consent in Acute Stroke Trials

et al. 2023

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The challenges of conducting hyperacute stroke research and obtaining informed consent have been increasingly recognized within the stroke research community in recent years. Deferral of consent, in which a patient is enrolled in a trial and then provides consent at some point thereafter, is increasingly used to enroll patients into hyperacute stroke trials in Canada and Europe, though it is not permitted in the United States. Deferral of consent offers several potential advantages – quicker door-to-randomization, increased enrolment, decreased selection bias – but these must be balanced against the risk of enrolling patients against their wishes. We seek to minimize the attendant risks of deferral of consent by offering practical guidance regarding how to conduct acute stroke trials using deferral of consent. Building upon existing guidelines and recent experiences with deferral of consent in acute stroke trials, we have developed a protocol for the use of deferral of consent that aims to maximize patient involvement while minimizing ethical and scientific risks.

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“…Authors from Canada described how the deferral of consent approach used in the AcT trial (Alteplase Compared to Tenecteplase) for patients with acute ischemic stroke could be used for standard care. 11 Meta-analyses on mobile stroke unit effectiveness identified favorable outcomes and a 30-minute reduction in onset to intravenous thrombolysis times, without safety concerns. 12 Beyond mobile stroke units, timely treatment was examined as an outcome of bypass and secondary transfer emergency care models in Canada, Australia, England, and China.…”

Section: Acute Stroke Care and Costsmentioning

confidence: 99%