Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the ENhanced Control of Hypertension and Thrombolysis strokE stuDy (ENCHANTED).
BACKGROUND
The ENhanced Control of Hypertension And Thrombolysis strokE stuDy trial is a 2 × 2 quasi-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial that is evaluating in thrombolysis-eligible acute ischemic stroke patients whether: (1) low-dose (0·6 mg/kg body weight) intravenous alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage compared with standard-dose (0·9 mg/kg body weight) intravenous alteplase; and (2) early intensive blood pressure lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of any intracerebral hemorrhage compared with guideline-recommended blood pressure control (systolic target <180 mmHg).


OBJECTIVE
To outline in detail the predetermined statistical analysis plan for the 'alteplase dose arm' of the 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 classified, and for each item, appropriate descriptive statistical analyses are planned with appropriate comparisons made between randomized groups. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described.


RESULTS
A statistical analysis plan was developed for the results of the alteplase dose arm of the study that is transparent, available to the public, verifiable, and predetermined before completion of data collection.


CONCLUSIONS
We have developed a predetermined statistical analysis plan for the ENhanced Control of Hypertension And Thrombolysis strokE stuDy alteplase dose arm which is to be followed to avoid analysis bias arising from prior knowledge of the study findings.
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
Craig S
CS
Anderson
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
Mark
M
Woodward
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.|Centre for Epidemiologic Research in Asia, Shiga University of Medical Sciences, Shiga University, Shiga, Japan.
Hisatomi
H
Arima
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
Xiaoying
X
Chen
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
Richard I
RI
Lindley
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
Xia
X
Wang
The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia.
John
J
Chalmers
D002545:Brain Ischemia / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000517:prevention & control; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D016037:Single-Blind Method; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
acute; alteplase; clinical trials; statistical analysis plan; stroke; thrombolysis