Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial
Isak Mazanti Cold,
Joshua Buron Feinberg,
Axel Brandes,
Ulla Davidsen,
Ulrik Dixen,
Helena Dominguez,
Uffe Jakob Ortved Gang,
Christian Gluud,
Rakin Hadad,
Kit Engedal Kristensen,
Doan Tuyet van Le,
Emil Eik Nielsen,
Michael Hecht Olsen,
Ole Dyg Pedersen,
Ilan Esra Raymond,
Ahmad Sajadieh,
Anne Merete Boas Soja,
Janus Christian Jakobsen
Affiliations
Isak Mazanti Cold
The Faculty of Health and Medical Sciences, The University of Copenhagen
Joshua Buron Feinberg
Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet
Axel Brandes
Department of Cardiology, Odense University Hospital
Ulla Davidsen
Department of Cardiology, Copenhagen University Hospital Bispebjerg and Frederiksberg
Ulrik Dixen
Department of Cardiology, University Hospital Amager and Hvidovre
Helena Dominguez
Department of Cardiology, Copenhagen University Hospital Bispebjerg and Frederiksberg
Uffe Jakob Ortved Gang
Department of Cardiology, Zealand University Hospital Roskilde
Christian Gluud
Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet
Rakin Hadad
Department of Cardiology, Copenhagen University Hospital Bispebjerg and Frederiksberg
Kit Engedal Kristensen
Department of Cardiology, University Hospital Amager and Hvidovre
Doan Tuyet van Le
Department of Cardiology, Zealand University Hospital Roskilde
Emil Eik Nielsen
Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet
Michael Hecht Olsen
Department of Internal Medicine – Section of Cardiology, Holbaek Hospital
Ole Dyg Pedersen
Department of Cardiology, Zealand University Hospital Roskilde
Ilan Esra Raymond
Department of Cardiology, University Hospital Amager and Hvidovre
Ahmad Sajadieh
Department of Cardiology, Copenhagen University Hospital Bispebjerg and Frederiksberg
Anne Merete Boas Soja
Department of Internal Medicine – Section of Cardiology, Holbaek Hospital
Janus Christian Jakobsen
Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet
Abstract Background A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. Methods The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for “site,” type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues. Discussion This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial. Trial registration Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.
