Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure

Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial

This trial will assess the efficacy and safety of QSG in CHF.

Background: Chronic heart failure(CHF), the final stage of various cardiovascular diseases, is a major public health problem associated with significant hospitalization rates, mortality, and huge health care costs, despite advances in the treatment and management of heart failure and heart failure related risk factors. Qishen granules(QSG), a Chinese herbal formula, is widely used by traditional chinese medicine(TCM) practitioners to treat CHF. Several animal experimental studies have showed that QSG can significantly relieve the heart failure symptoms of CHF rat models. However, there is yet no standard clinical trial to assess that. Thus, the investigators are conducting this study to evaluate the efficacy and safety of QSG in a large, varied population.

Methods/Design: This study is designed as a randomized, multi-center, placebo-controlled, double-blind , parallel-group clinical trial. An established total of 200 patients with CHF will be recruited and randomly allocated to either the QSG treatment group or the placebo group (a 1:1 ratio). The patients will receive QSG or placebo granules twice daily for 12 weeks. The primary endpoint is the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide(NT-proBNP) level during 12 weeks of treatment. The secondary endpoints consist of composite cardiac events (CCEs), New York Heart Association (NYHA) functional classification, 6-minute walking distance (6MWD), Left ventricular ejection fraction, patient quality of life and TCM syndrome integral scale.

Discussion: This trial will assess the efficacy and safety of QSG in CHF.

Inclusion Criteria:

1. age between 18 and 75 years;
2. clinical findings of CHF for at least 3 months prior to screening;
3. CHF caused by coronary heart disease and hypertension, which is diagnosed according to the Chinese guidelines published in 2014 for the diagnosis and management of CHF;
4. clinically stable condition with an NYHA functional class of II to III and an optimal medical treatment with a fixed dosage for at least 2 weeks;
5. a documented left ventricular ejection fraction (LVEF) ≤40% and a serum NT-proBNP level ≥450 pg/ml;
6. CHF of Qi deficiency and blood stasis syndrome;
7. provision of written informed consent.

Exclusion Criteria:

1. CHF complicated with severe valvular disease, congenital heart disease, pericardial disease, cardiomyopathy, unstable angina, acute myocardial infarction(in recent 4 weeks), cardiogenic shock, acute myocarditis, infective endocarditis, uncontrolled severe cardiac arrhythmia with hemodynamic changes;
2. pulmonary heart disease, pulmonary hypertension caused by acute or chronic pulmonary embolism or cerebral apoplexy in recent 6 months;
3. severe hepatic inadequacy with alanine aminotransferase or alkaline phosphatase levels >2 times the upper normal limit, renal inadequacy with a creatinine clearance rate>20% or a serum creatinine level>3mg/dl (>265μmol/L), severe electrolyte imbalance, severe hematologic disease, malignant tumor, diabetes mellitus with severe complications, or severe endocrine diseases such as hyperthyroidism and hypothyroidism;
4. acute infection confirmed by any one of the following 3 tips: 1) fever; 2) a white blood cell count>10×109/L and a percentage of neutrophils>85%; 3) shadows on chest X-ray;
5. uncontrolled blood pressure or fibrosis in other organs;
6. CHF of yin deficiency according to TCM syndrome differentiation;
7. pregnancy or breastfeeding;
8. psychiatric or infectious disease;
9. patients who have participated in other clinical trials in the past two months.