Long-term efficacy and impact on rehospitalization of Qishen granules in patients with hypertension and heart failure with reduced ejection fraction: a multicenter, randomized, double-blind, placebo-controlled trial protocol.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) represents a severe manifestation or terminal stage of various cardiac diseases. Long-term hypertension frequently leads to pathological changes such as ventricular remodeling, resulting in HFrEF. Despite continuous advancements in medications targeting hypertension complicated by HFrEF, the five-year survival rate for patients remains below 50%. Chinese Medicine (CM) demonstrates favorable long-term efficacy in managing HFrEF and reducing readmission rates. Focusing on the primary symptoms of HFrEF, we innovatively proposed the syndrome pattern "Toxic Pathogen Syndrome" and developed the effective compound formula Qi Shen Granules (QSG). This trial aims to conduct a prospective clinical study to evaluate the efficacy and safety of QSG in patients with hypertension and HFrEF. METHODS: This is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial. A total of 220 eligible participants with hypertension and HFrEF will be recruited and randomized in a 1:1 ratio to receive either QSG or placebo for 12 weeks. All participants received guideline-directed treatment for hypertension and HFrEF throughout the study period. The primary outcome is the improvement rate in plasma NT-proBNP levels from baseline to endpoint and the six-minute walk test. Secondary outcomes include echocardiographic parameters, NYHA functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Heart Failure Toxicity Scale. Safety measures, including liver and kidney function blood tests and adverse events, were used to assess QSG safety. We also conducted follow-up assessments at weeks 26 and 52 to evaluate patient readmission rates and the occurrence of cardiovascular adverse events. DISCUSSION: The results of this study may establish clinical evidence supporting the therapeutic benefits and safety of QSG in the management of hypertension with HFrEF. CLINICAL TRIAL REGISTRATION: http://itmctr.ccebtcm.org.cn/, ITMCTR2025000665.