TY - JOUR

T1 - Lenient rate control versus strict rate control for atrial fibrillation

T2 - a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial

AU - Cold, Isak Mazanti

AU - Feinberg, Joshua Buron

AU - Brandes, Axel

AU - Davidsen, Ulla

AU - Dixen, Ulrik

AU - Dominguez, Helena

AU - Gang, Uffe Jakob Ortved

AU - Gluud, Christian

AU - Hadad, Rakin

AU - Kristensen, Kit Engedal

AU - van Le, Doan Tuyet

AU - Nielsen, Emil Eik

AU - Olsen, Michael Hecht

AU - Pedersen, Ole Dyg

AU - Raymond, Ilan Esra

AU - Sajadieh, Ahmad

AU - Soja, Anne Merete Boas

AU - Jakobsen, Janus Christian

N1 - Funding Information: MHO reports grants from Novo Nordic Foundation outside the submitted work. AB reports personal fees from Bayer, grants from Biotronik, personal fees from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb, personal fees from MSD, and grants from Theravance, outside the submitted work. UD reports a research grant from Bayer and personal fees from Pfizer, outside the submitted work. HD reports grants from the innovation fund of Grand solutions with the Danish company Cortrium APS as one of the partners and a subcontract with the Danish company Visikon APS, with funding from Danida Research Center, both outside the submitted work. All other authors report no known competing interests. Funding Information: Open access funding provided by Royal Danish Library. The trial was initiated by clinicians at the participating hospitals. The research salary for research nurses is partly funded by the Region of Southern Denmark and Region Zealand joint research fund 2018 for year 1. The salary of the lead author for years 2 and 3 is provided by the Danish Heart Foundation grant number 19-R134-A8959-22123. The salary for year 1 is granted by the University of Southern Denmark. The participating departments support the trial by dedicating work hours of the other investigators, supportive staff, logistical support, and administrative support. The trial is investigator-initiated. Holbaek Hospital is the sponsor, and the Region Zealand is the data controller. The study sponsors and funders had no influence on the design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. The Danish Heart Foundation requires to be notified by email when a publication is accepted. Roles and responsibilities of additional parties are described in the protocol. Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Atrial fibrillation

KW - Randomized trial

KW - Rate control

KW - Statistical analysis plan

U2 - 10.1186/s13063-023-07247-7

DO - 10.1186/s13063-023-07247-7

M3 - Journal article

C2 - 37005636

AN - SCOPUS:85151316971

VL - 24

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 250

ER -