TY - JOUR
T1 - Rationale, design, and progress of the ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED) trial
T2 - An international multicenter 2×2 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
AU - For the ENCHANTED investigators
AU - Huang, Yining
AU - Sharma, Vijay K.
AU - Robinson, Thompson
AU - Lindley, Richard I.
AU - Chen, Xiaoying
AU - Kim, Jong Sung
AU - Lavados, Pablo
AU - Olavarría, Verónica
AU - Arima, Hisatomi
AU - Fuentes, Sully
AU - Nguyen, Huy Thang
AU - Lee, Tsong Hai
AU - Parsons, Mark W.
AU - Levi, Christopher
AU - Demchuk, Andrew M.
AU - Bath, Philip M.W.
AU - Broderick, Joseph P.
AU - Donnan, Geoffrey A.
AU - Martins, Sheila
AU - Pontes-Neto, Octavio M.
AU - Silva, Federico
AU - Pandian, Jeyaraj
AU - Ricci, Stefano
AU - Stapf, Christian
AU - Woodward, Mark
AU - Wang, Jiguang
AU - Chalmers, John
AU - Anderson, Craig S.
N1 - Publisher Copyright:
© 2015 World Stroke Organization.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Rationale: 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 (0·6mg/kg) is more efficacious than standard-dose (0·9mg/kg) iv rt-PA, and guidelines recommend reducing systolic BP to <185mmHg before and <180mmHg after use of iv rt-PA, despite observational studies indicating better outcomes at much lower (<140mmHg) systolic BP levels in this patient group. Aims: The study aims to assess in thrombolysis-eligible AIS patients whether: (i) low-dose (0·6mg/kg body weight; maximum 60mg) iv rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage (sICH) compared to standard-dose (0·9mg/kg body weight; maximum 90mg) iv rt-PA; and (ii) early intensive BP lowering (systolic target 130-140mmHg) has superior efficacy and lower risk of any ICH compared to guideline-recommended BP control (systolic target<180mmHg). Design: 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. Study outcomes: 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. Results: 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. Conclusions: 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.
AB - Rationale: 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 (0·6mg/kg) is more efficacious than standard-dose (0·9mg/kg) iv rt-PA, and guidelines recommend reducing systolic BP to <185mmHg before and <180mmHg after use of iv rt-PA, despite observational studies indicating better outcomes at much lower (<140mmHg) systolic BP levels in this patient group. Aims: The study aims to assess in thrombolysis-eligible AIS patients whether: (i) low-dose (0·6mg/kg body weight; maximum 60mg) iv rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage (sICH) compared to standard-dose (0·9mg/kg body weight; maximum 90mg) iv rt-PA; and (ii) early intensive BP lowering (systolic target 130-140mmHg) has superior efficacy and lower risk of any ICH compared to guideline-recommended BP control (systolic target<180mmHg). Design: 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. Study outcomes: 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. Results: 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. Conclusions: 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.
KW - Acute ischaemic stroke
KW - Alteplase
KW - Dose
KW - Hypertension
KW - Rt-PA
KW - Thrombolysis
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U2 - 10.1111/ijs.12486
DO - 10.1111/ijs.12486
M3 - Article
C2 - 25832995
AN - SCOPUS:84931572199
SN - 1747-4930
VL - 10
SP - 778
EP - 788
JO - International Journal of Stroke
JF - International Journal of Stroke
IS - 5
ER -