Rationale, design, and progress of the ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED) trial: An international multicenter 2x2 quasi-factorial randomized controlled trial of low- vs. standard-dose rt-PA and early intensive vs. guideline-recommended blood pressure lowering in patients with acute ischaemic stroke eligible for thrombolysis treatment.
Journal
International Journal of Stroke
ISSN
1747-4930
1747-4949
Date Issued
2015
Author(s)
Yining Huang
Vijay K. Sharma
Thompson Robinson
Richard I. Lindley
Xiaoying Chen
Jong Sung Kim
Hisatomi Arima
Sully Fuentes
Huy Thang Nguyen
Tsong-Hai Lee
Mark W. Parsons
Christopher Levi
Andrew M. Demchuk
Philip M. W. Bath
Joseph P. Broderick
Geoffrey A. Donnan
Sheila Martins
Octavio M. Pontes-Neto
Federico Silva
Jeyaraj Pandian
Stefano Ricci
Christian Stapf
Mark Woodward
Jiguang Wang
John Chalmers
Craig S. Anderson
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:sec><jats:title>Rationale</jats:title><jats:p> Controversy exists over the optimal dose of intravenous (iv) recombinant tissue plasminogen activator (rt-PA) and degree of blood pressure (BP) control in acute ischaemic stroke (AIS). Asian studies suggest low-dose (0·6 mg/kg) is more efficacious than standard-dose (0·9 mg/kg) iv rt-PA, and guidelines recommend reducing systolic BP to <185 mmHg before and <180 mmHg after use of iv rt-PA, despite observational studies indicating better outcomes at much lower (<140 mmHg) systolic BP levels in this patient group. </jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p> The study aims to assess in thrombolysis-eligible AIS patients whether: (i) low-dose (0·6 mg/kg body weight; maximum 60 mg) iv rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage (sICH) compared to standard-dose (0·9 mg/kg body weight; maximum 90 mg) iv rt-PA; and (ii) early intensive BP lowering (systolic target 130–140 mmHg) has superior efficacy and lower risk of any ICH compared to guideline-recommended BP control (systolic target < 180 mmHg). </jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p> The ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED) trial is an independent, 2 × 2 quasi-factorial, active-comparison, prospective, randomized, open blinded endpoint (PROBE), clinical trial that is evaluating Arm [A] ‘rt-PA dose’ and/or Arm [B] ‘BP control’, using central Internet randomization and data collection in patients fulfilling local criteria for thrombolysis and clinician uncertainty over the study treatments. The treatment arms will be analyzed separately. </jats:p></jats:sec><jats:sec><jats:title>Study outcomes</jats:title><jats:p> The primary study outcome in both trial Arms is death or disability according to the modified Rankin scale (mRS, scores 2–6) assessed at 90 days. Secondary outcomes include sICH, any ICH, a shift (‘improvement’) in function across mRS scores, separately on death and disability, early neurological deterioration, recurrent major vascular events, health-related quality of life, length of hospital stay, need for permanent residential care, and health care costs. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Following launch of the trial in February 2012, the study has recruited more than 2500 patients across a global network of approximately 100 sites in 15 countries. The required sample sizes are 3300 for Arm [A] and 2300 for Arm [B], which will provide >90% power to detect non-inferiority of low-dose iv rt-PA and superiority of intensive BP lowering on the primary clinical outcome, respectively. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> Low-dose iv rt-PA and early intensive BP lowering could provide more affordable and safer use of thrombolysis treatment for patients with AIS worldwide. </jats:p></jats:sec>
Subjects
acute ischaemic stroke
;
alteplase
;
dose
;
hypertension
;
rt-pa
;
thrombolysis