Systematic review of first-in-human and early phase clinical trials for surgically implantable biological mitral valve substitutes

• Published in: Journal of cardiothoracic surgery Vol. 18; no. 1; pp. 1 - 348
• Main Authors: Sazzad, Faizus, Tan, Ying Kiat, Chan, Li Xuan Beverly, Moideen, Irwan Shah Bin Mohd, Gohary, Abdulrahman El, Stevens, John C, Ramanathan, K. R, Kofidis, Theo
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 30-11-2023; BioMed Central; BMC
• Subjects: Bias; Bioprosthesis; Citation management software; Clinical trial; Clinical trials; First-in-human; Heart; Heart valve diseases; Heart valve prosthesis; Heart valves; Implants, Artificial; Medical research; Medicine, Experimental; Mitral valve; Product development; Prostheses; Prosthesis; Prosthetics; Review; Subgroups; Surgical implants; Systematic review
• ISSN: 1749-8090; 1749-8090
• DOI: 10.1186/s13019-023-02464-2

Abstract
Background
The aim of this review was the creation of uniform protocols to carry out and disclose First-In-Human and preliminary clinical trials of biological mitral valve replacement. The need for consistent methodology in these early trials was highlighted by the observation of significant variability in the methods and protocols used across different research.
Methods
An extensive search through six major databases was carried out to retrieve First-In-Human (FIH) clinical studies evaluating surgically implanted bio-prostheses in the mitral position.
Results
Following the PRISMA guideline, a systematic search identified 2082 published articles until March 2023. After removing duplicates (189), 1862 citations were screened, resulting in 22 eligible studies with 3332 patients for analysis. The mitral valve prostheses in these studies ranged from 21 to 37 mm, with the 29 mm size being most prevalent. Patient numbers varied, with the FIH subgroup including 31 patients and the older subgroup including 163 patients. Average study durations differed: the older subgroup lasted 4.57 years, the FIH subgroup 2.85 years, and the early phase studies spanned 8.05 years on average.
Conclusion
FIH clinical report is essential to assess the significance of clinical data required for a “de novo” surgical implant. In addition, understanding the performance of the device, and recognizing the difficulties associated with the innovation constitute important lessons. These insights could be beneficial for the development of bioprosthetic heart valves and formulating a protocol for an FIH clinical trial.