The last quinquennium of on-going trials in cardiac rehabilitation around the globe: an analysis of the International Clinical Trial Registry Platform

Abstract Background There has been a growing emphasis on cardiac rehabilitation (CR) around the world. Nevertheless, much of the literature comes from high-income countries, even though the burden of cardiovascular disease is the highest in low-middle income countries (LMICs). Purpose This study was therefore aimed at understanding the current state of on-going trials in CR, to compare differences in trials across regions of the world and compare it across economic regions of the world. Methods A search was conducted in the WHO International Clinical Trial Registry Platform for trials on CR. Only studies that were not yet recruiting or currently recruiting for the duration of January 1, 2020 to December 31, 2024 were considered for inclusion into the study. Results A total of 1097 trials were identified, from which 572 trials met the time period criteria and 385 were currently on-going. Among them, majority were interventional studies (n=332; 86.2%) and the remaining (n=49;12.7%) were observational, of which three (0.8%) were registry-based studies. Most studies were from the Western Pacific region (164; 42.6%), and from high-income countries (179; 46.5%). The top five countries leading CR research were China (including Taiwan) (90), India (39), United States of America (35), and Japan and Iran (28 each) (Figure 1). Sample sizes recruited into the trials ranged from 5-10,000 with a median of 90. The highest median sample size was from the Western Pacific Region (N=110) and from the high-income category (N=100). Among the interventional trials (n=332), RCTs were common (251; 75.6%) with a small fraction (1.3%) being factorial trials, cluster trials, hybrid implementation trials and step wedged trials. Among the RCTs (251), details in the method of randomization were unclear in 167 (66.5%), as was the method of allocation (243; 96.8%). Blinding, however, was present in 136 (54.1%). Exercise capacity and quality of life were the common primary outcomes (Figure 2), though 44% had more than one primary outcome (range: 2-14). Multinational, multicentric studies were few (n=3), as were multicentric studies within countries (48/306; 15.6%). Funding was available for 211 (54.8%) studies with more funding in high-income regions (111; 28.8%) than LMIC (19; 4.9%) with the Western Pacific region having the most funded CR research (94; 24.4%). Conclusion CR research continues to be more in high-income countries, with only India contributing as a LMIC. Sample sizes vary considerably, as do the number of multicentric studies. Methodological concerns appear to exist with respect to randomization, allocation methods, presence of blinding and number of primary outcomes. This could have implications for trial registries to ensure uniformity in methodological definitions. The need for enhancing research capacity and funding cannot be understated as this would be vital for improving the methodological rigor and scaling up of CR trials around the world.Global distribution of trials Word cloud of primary outcome measures