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 - © 2023. The Author(s).
PY - 2023/4/1
Y1 - 2023/4/1
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 - Humans
KW - Atrial Fibrillation/diagnosis
KW - Stroke Volume
KW - Ventricular Function, Left
KW - Research Design
KW - Denmark
KW - Treatment Outcome
KW - Statistical analysis plan
KW - Atrial fibrillation
KW - Randomized trial
KW - Rate control
U2 - 10.1186/s13063-023-07247-7
DO - 10.1186/s13063-023-07247-7
M3 - Journal article
C2 - 37005636
SN - 1745-6215
VL - 24
JO - Trials
JF - Trials
M1 - 250
ER -