Minimal sufficient balance randomization for sequential randomized controlled trial designs: results from the ESCAPE trial

Tolulope T Sajobi, Gurbakhshash Singh, Mark W Lowerison, Jordan Engbers, Bijoy K Menon, Andrew M Demchuk, Mayank Goyal, Michael D Hill, Tolulope T Sajobi, Gurbakhshash Singh, Mark W Lowerison, Jordan Engbers, Bijoy K Menon, Andrew M Demchuk, Mayank Goyal, Michael D Hill

Abstract

Background: We describe the implementation of minimal sufficient balance randomization, a covariate-adaptive randomization technique, used for the "Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times" (ESCAPE) trial.

Methods: The ESCAPE trial is a prospective, multicenter, randomized clinical trial that enrolled subjects with the following main inclusion criteria: less than 12 h from symptom onset, age 18 years or older, baseline NIHSS score > 5, ASPECTS score > 5 and computed tomography angiography (CTA) evidence of carotid T/L or M1-segment middle cerebral artery (MCA) occlusion, and at least moderate collaterals by CTA. Patients were randomized using a real-time, dynamic, Internet-based, minimal sufficient balance randomization method that balanced the study arms with respect to baseline covariates including age, sex, baseline NIHSS score, site of arterial occlusion, baseline ASPECTS score and treatment with intravenously administered alteplase.

Results: Permutation-based tests of group differences confirmed group balance across several baseline covariates including sex (p = 1.00), baseline NIHSS score (p = 0.95), site of arterial occlusion (p = 1.00), baseline ASPECTS score (p = 0.28), treatment with intravenously administered alteplase (p = 0.31), and age (p = 0.67).

Conclusion: Results from the ESCAPE trial demonstrate the feasibility and the benefit of this covariate adaptive randomization scheme in small-sample trials and for data monitoring endeavors.

Trial registration: ESCAPE trial - NCT01778335 - at www.clinicaltrials.gov . Registered on 29 January 2013.

Keywords: Data monitoring; Endovascular therapy; Minimal sufficient balance; Randomization; Stroke trial.

Conflict of interest statement

Authors’ information

Displayed on the title page.

Ethics approval and consent to participate

All subjects or their surrogate provided written informed consent and the study protocol was approved at each site by the Local Ethics Board or equivalent. The principal ethics central site Ethics Committee was the Conjoint Human Research Ethics Board at the University of Calgary. The ethics file reference number was: REB25048.

Consent for publication

All subjects or their surrogate provided consent for publication. Written informed consent was obtained from the participant for publication of their individual details and accompanying images in this manuscript. The Consent Form is held by the authors/by the authors’ institution/in the patients’ clinical trial binder and is available for review by the Editor-in-Chief.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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