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Randomized Controlled Trial
. 2023;52(3):251-254.
doi: 10.1159/000526384. Epub 2022 Sep 5.

Statistical Analysis Plan for the INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial: A Stepped-Wedge Cluster Randomized Controlled Trial

Laurent Billot  1 , Lili Song  1   2 , Xin Hu  3 , Lu Ma  3 , Menglu Ouyang  1   2 , Xiaoying Chen  1 , Chao You  3 , Craig S Anderson  1   2 ; INTERACT3 Investigators
Affiliations
Randomized Controlled Trial

Statistical Analysis Plan for the INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial: A Stepped-Wedge Cluster Randomized Controlled Trial

Laurent Billot et al. Cerebrovasc Dis. 2023.

Abstract

The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) is an international, multicenter, stepped-wedge (4 phases/3 steps) cluster randomized trial involving 110 hospitals in mainly low- and middle-income countries during 2017-2022. The aim is to determine the effectiveness of a goal-directed care bundle of intensive blood pressure (BP) lowering, glycemic control, antipyrexia, and anticoagulation reversal treatment versus usual standard of care, in patients with acute intracerebral hemorrhage (ICH). After a "usual care" period, hospitals were randomly allocated to implementing care-bundle protocols for control targets (systolic BP <140 mm Hg; glucose 6.1-7.8/7.8-10.0 mmol/L according to diabetes mellitus status; temperature ≤37.5°C; normalization of anticoagulation). A sample size of 8,360 patients (mean 19 per phase per site) provides 90% power (α = 0.05) for a 5.6% absolute improvement in the primary outcome of scores on the modified Rankin scale at 6 months, analyzed by ordinal logistic regression. A detailed statistical analysis plan (SAP) was developed to prespecify the method of analysis for all outcomes and key variables collected in the trial. The primary analysis will use ordinal logistic regression adjusted for the stepped-wedge design. The SAP also includes planned sensitivity analyses, including covariate adjustments, missing data imputations, and subgroup analysis. This SAP allows transparent, verifiable, and prespecified analyses in consideration of the challenges in conducting the study during the COVID pandemic. It also avoids analysis bias arising from prior knowledge of the findings in determining the benefits and harms of a care bundle in acute ICH.

Trial registration: ClinicalTrials.gov NCT03209258.

Keywords: Clinical trial; Cluster; Hypertension; Intracerebral hemorrhage; Statistical analysis plan; Stroke.

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Conflict of interest statement

Dr. Lili Song and Prof. Craig Anderson report receiving grant funding from Takeda and Credit paid to their institution and receiving lecture fees and travel reimbursement from Takeda. Mr. Laurent Billot, Dr. Xin Hu, Dr. Lu Ma, Dr. Menglu Ouyang, Dr. Xiaoying Chen, and Prof. Chao You have no relevant disclosures.

References

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