INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial
Journal
Trials
ISSN
1745-6215
Date Issued
2021
Author(s)
Lili Song
Xin Hu
Lu Ma
Xiaoying Chen
Menglu Ouyang
Laurent Billot
Qiang Li
Carlos Abanto
Octavio Marques Pontes-Neto
Arauz Antonio
Mohammad Wasay
Asita de Silva
Nguyen Huy Thang
Jeyaraj Durai Pandian
Kolawole Wasiu Wahab
Chao You
Craig S. Anderson
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1–7.8 mmol/L and 7.8–10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (<jats:italic>α</jats:italic> = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions.</jats:p>
</jats:sec><jats:sec>
<jats:title>Discussion</jats:title>
<jats:p>As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established.</jats:p>
</jats:sec><jats:sec>
<jats:title>Trial registration</jats:title>
<jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">ClinicalTrials.gov</jats:ext-link> NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017</jats:p>
</jats:sec>
<jats:title>Background</jats:title>
<jats:p>Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH (< 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic < 140 mmHg; glucose control, target 6.1–7.8 mmol/L and 7.8–10.0 mmol/L in those without and with diabetes mellitus, respectively; anti-pyrexia treatment to target body temperature ≤ 37.5 °C; and reversal of anticoagulation, target international normalized ratio < 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The sample size of 8360 subjects provides 90% power (<jats:italic>α</jats:italic> = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions.</jats:p>
</jats:sec><jats:sec>
<jats:title>Discussion</jats:title>
<jats:p>As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established.</jats:p>
</jats:sec><jats:sec>
<jats:title>Trial registration</jats:title>
<jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">ClinicalTrials.gov</jats:ext-link> NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017</jats:p>
</jats:sec>
Cite this document
Song, L., Hu, X., Ma, L., Chen, X., Ouyang, M., Billot, L., Li, Q., Muñoz-Venturelli, P., Abanto, C., Pontes-Neto, O. M., Antonio, A., Wasay, M., Silva, A. D., Thang, N. H., Pandian, J. D., Wahab, K. W., You, C., Anderson, C. S., & for the INTERACT3 investigators. (2021). INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (Interact3): Study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial. Trials, 22(1), 943. https://doi.org/10.1186/s13063-021-05881-7
Subjects
stepped-wedge cluster-randomized trial
;
clinical trial
;
care bundle
;
management
;
intracerebral hemorrhage
;
stroke
;
adolescent
;
adult
;
anticoagulation reversal
;
blood pressure
;
cerebral hemorrhage
;
critical care
;
humans
;
multicenter studies as topic
;
patient care bundles
;
quality of life
;
randomized controlled trials as topic
;
adult
;
anticoagulation
;
article
;
blood pressure
;
brain hemorrhage
;
care bundle
;
diabetes mellitus
;
female
;
fever
;
glycemic control
;
human
;
low income country
;
major clinical study
;
male
;
middle income country
;
quality of life
;
rankin scale
;
young adult
;
adolescent
;
blood pressure
;
brain hemorrhage
;
intensive care
;
multicenter study (topic)
;
randomized controlled trial (topic)