Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy

Craig S Anderson; Mark Woodward; Hisatomi Arima; Xiaoying Chen; Richard I Lindley; Xia Wang; John Chalmers; Thompson G Robinson

doi:10.1177/1747493018806170

Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy

Int J Stroke. 2019 Jul;14(5):555-558. doi: 10.1177/1747493018806170. Epub 2018 Oct 9.

Authors

Craig S Anderson^{1

2

3}, Mark Woodward^{1

4}, Hisatomi Arima^{1

5}, Xiaoying Chen^{1

6}, Richard I Lindley⁷, Xia Wang¹, John Chalmers¹, Thompson G Robinson^{8

9}

Affiliations

¹ 1 The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
² 2 The George Institute China at Peking University Health Science Center, Beijing, PR China.
³ 3 Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, NSW, Australia.
⁴ 4 The George Institute for Global Health, University of Oxford, Oxford, UK.
⁵ 5 Department of Public Health, Fukuoka University, Fukuoka, Japan.
⁶ 6 Sydney Medical School, University of Sydney, NSW, Australia.
⁷ 7 Westmead Clinical School, University of Sydney, NSW, Australia.
⁸ 8 Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
⁹ 9 NIHR Leicester Biomedical Research Centre, Leicester, UK.

PMID: 30299230
DOI: 10.1177/1747493018806170

Abstract

Background: The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A - low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B - early intensive blood pressure (BP) lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding.

Objective: To outline in detail and make public the predetermined statistical analysis plan (SAP) for the 'BP control' arm of this study.

Methods: All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described.

Results: A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection.

Conclusions: We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings.

Clinical trial registration: ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry - India (REF/2017/05/014334).

Keywords: Hypertension; alteplase; clinical trials; statistical analysis plan; stroke; thrombolysis.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Data Interpretation, Statistical*
Dose-Response Relationship, Drug
Humans
Hypertension / complications
Hypertension / drug therapy*
Randomized Controlled Trials as Topic
Stroke / complications
Stroke / drug therapy*
Tissue Plasminogen Activator / therapeutic use*

Substances

Tissue Plasminogen Activator

Associated data

ClinicalTrials.gov/NCT01422616
ISRCTN/ISRCTN82387104
ANZCTR/ACTRN12611000236998
EudraCT/2011-005545-12
CTRI/REF/2017/05/014334