Additional file 1 of Statistical analysis plan for a randomized controlled trial examining pedometer-based walking intervention in patients with heart failure with reduced ejection fraction: the WATCHFUL trial

Additional file 1. Statistical Analysis Plan Checklist

Baseline characteristics of patients after matching according to type of heart failure.

<p>*/**Statistical significance of differences between groups tested by the ML chi-square test for categorical variables and by the independent Student’s <i>t</i>-test for continuous variables</p><p>*/**p<0.05/p<0.001</p><p>^aParameters used in a logistic regression model of a propensity score</p><p>^bMedication at discharge was computed on patients who were alive after discharge</p><p>LVEF—left ventricular ejection fraction, BP—blood pressure, MI—myocardial infarction, TIA—transient ischemic attack, PCI—percutaneous coronary intervention, CABG—coronary artery bypass graft, PM—pacemaker, ICD—implantable cardioverter–defibrillator, CRT—cardiac resynchronization therapy, COPD—chronic obstructive pulmonary disease, ARB—angiotensin-2 receptor blockers.</p><p>Baseline characteristics of patients after matching according to type of heart failure.</p

Baseline characteristics of patients before and after matching.

<p>*/**Statistical significance of differences between groups was tested by the ML chi-square test for categorical variables and by the independent Student’s <i>t</i>-test for continuous variables</p><p>*/**p<0.05/p<0.001</p><p>^aParameter used in a logistic regression model of a propensity score</p><p>^bParameter was not known for all patients, and statistics were computed on a reduced basis</p><p>^cMedication at discharge was computed on patients who were alive after discharge</p><p>LVEF—left ventricular ejection fraction, BP—blood pressure, MI—myocardial infarction, TIA—transient ischemic attack, PCI—percutaneous coronary intervention, CABG—coronary artery bypass graft, PM—pacemaker, ICD—implantable cardioverter–defibrillator, CRT—cardiac resynchronization therapy, COPD—chronic obstructive pulmonary disease, ARB—angiotensin-2 receptor blockers.</p><p>Baseline characteristics of patients before and after matching.</p

Thirty-day mortality according to the BMI category and type of heart failure.

<p>Thirty-day mortality according to the BMI category and type of heart failure.</p

Long-term mortality for all patients according to a BMI of 25 kg/m² in a non-balanced and balanced dataset and for ADHF and <i>de novo</i> AHF patients.

<p>Long-term mortality for all patients according to a BMI of 25 kg/m² in a non-balanced and balanced dataset and for ADHF and <i>de novo</i> AHF patients.</p

Definition of datasets.

<p>Definition of datasets.</p

Effects of hypothermia vs normothermia on societal participation and cognitive function at 6 months in survivors after out-of-hospital cardiac arrest

Importance: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. Objectives: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. Design, Setting, and Participants: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Interventions: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Main outcomes and measures: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes.ResultsAt 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,−0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,−0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%).ConclusionsIn this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.</p