Drug Design, Development and Therapy (Jun 2023)
Clinical Trials in Hypertrophic Cardiomyopathy Therapy: A Comprehensive Analysis of Trials Registered in Global Clinical Databases
Abstract
Huan Zhang,1,2,* Cheng Yu,1,* Yuanling Cheng,1 Zhi Chen,2 Min Chen,2 Wangan He,1 Zhigang Jin,1 Shaoqian Cai,1 Lijuan Yu2 1Department of Cardiology, China Resources & Wisco General Hospital, Wuhan University of Science and Technology, Wuhan, People’s Republic of China; 2Wuhan University of Science and Technology Medical College, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaoqian Cai; Zhigang Jin, Department of Cardiology, China Resources & Wisco General Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, 430080, People’s Republic of China, Email [email protected]; [email protected]: With the disappointing results associated with the use of cardiac myosin inhibitors in the treatment of hypertrophic cardiomyopathy (HCM), the development of new therapies in clinical trials for HCM has rapidly increased. We assessed the characteristics of therapeutic intervention in HCM registered on ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP).Methods: We conducted a cross-sectional, descriptive study of clinical trials for therapeutic intervention in HCM registered on ClinicalTrials.gov and ICTRP.Results: This study analyzed 137 registered trials. Regarding study designs of these trials, 77.37% were purpose of treatment, 59.12% were randomized, 50.36% were parallel assignment, 45.26% were performed with masking, 48.18% recruited less than 50 participants, and 27.74% were Phase 2 trials. In total, 67 trials were new drug trials, of which 35 drugs were tested in these trials, and 13 trials involved treatment with mavacamten. Of these 67 clinical drug trials, 44.78% of trials involved the study of amines, and 16.42% involved 1-ring heterocyclic compounds. Regarding the NCI Thesaurus Tree, 23.81% of trials involved myosin inhibitors, 23.81% of trials involved drugs belonging to agents affecting the cardiovascular system, and 20.63% were involved in testing cation channel blockers. The drug-target network showed that myosin-7, potassium voltage-gated channel subfamily h member 2, beta-1 adrenergic receptor, carnitine o-palmitoyltransferase 1, and liver isoform were the most targeted pathways of the clinical trials analyzed in the drug-target network.Conclusion: The number of clinical trials investigating therapeutic interventions for HCM has increased in recent years. Ultimately, recent HCM therapeutic clinical trials generally did not incorporate either randomized controlled trials or masking and were small studies recruiting fewer than 50 participants. Although recent research has focused on targeting myosin-7, the molecular signaling mechanisms involved in the pathogenesis of HCM have the potential to elucidate novel target pathways.Keywords: clinical trials, obstructive hypertrophic cardiomyopathy, nonobstructive hypertrophic cardiomyopathy, myosin-7, amines, myosin inhibitors
