Efficacy and Safety of Kuoxin Formula in the Treatment of Dilated Cardiomyopathy-Related Heart Failure: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial

Qiong Wu; Shiying An; RueyJyh Lee; Dongwen Gao; Yinyifan Zhou; Longping Peng; Chunrui Hu; Lei Yao; Chang Zhou; Li Zhou; Junjie Gao; Min Cao; Meijiao Mao; Guanghao Li; Bing Deng; Yingjia Xu; Youhua Wang

doi:10.2147/IJGM.S461765

Efficacy and Safety of Kuoxin Formula in the Treatment of Dilated Cardiomyopathy-Related Heart Failure: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial

Int J Gen Med. 2024 May 6:17:1909-1921. doi: 10.2147/IJGM.S461765. eCollection 2024.

Authors

Qiong Wu^#¹, Shiying An^#¹, RueyJyh Lee¹, Dongwen Gao², Yinyifan Zhou¹, Longping Peng¹, Chunrui Hu¹, Lei Yao³, Chang Zhou⁴, Li Zhou⁵, Junjie Gao⁶, Min Cao¹, Meijiao Mao¹, Guanghao Li¹, Bing Deng¹, Yingjia Xu⁴, Youhua Wang¹

Affiliations

¹ Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
² Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
³ Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
⁴ Department of Cardiology, Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai, People's Republic of China.
⁵ Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People's Republic of China.
⁶ Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

^# Contributed equally.

Abstract

Background: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients' quality of life. This trial aims to further evaluate KXF's safety and efficacy in managing DCM-related heart failure.

Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee's heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.

Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.

Trial registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.

Keywords: Kuoxin Formula; clinical trials; dilated cardiomyopathy; heart failure; traditional Chinese medicine.

Grants and funding

The study design has been supported by National Natural Science Foundation (82004319) and Shanghai Municipal Health Commission, Excellent youth talent training program (2022YQ040) and Science and Technology Committee of Shanghai Municipality project (22Y11922000) and Clinical Research Plan of SHDC(SHDC2020CR4054) and Medical Characteristic Specialty of Minhang District Funding Project Plan (2020MWTZB01).