Clinical trial NCT03027375: Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure
Official title: Evaluating the Safety and Efficacy of Qishen Granules Among Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Heart Failure
Cardiovascular Diseases
Keywords: chronic heart failure
traditional Chinese medicine
Qishen granules
Lead sponsor: Beijing University of Chinese Medicine
Sponsor class: OTHER
Collaborators: name: China-Japan Friendship Hospital
name: Zhengzhou Hospital of Traditional Chinese Medicine
name: Beijing Anzhen Hospital
First posted: 2017-01-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide
timeFrame: 12weeks
Secondary outcomes:
measure: composite cardiac events
timeFrame: 4weeks,8weeks,12weeks
measure: New York Heart Association (NYHA) functional classification
timeFrame: 4weeks,8weeks,12weeks
measure: 6-minute walking distance
timeFrame: 4weeks,8weeks,12weeks
measure: Left ventricular ejection fraction
timeFrame: 12weeks
measure: Chronic Heart Failure Quality of Life Scale of Integrated Chinese and Western Medicine
timeFrame: 4weeks,8weeks,12weeks
measure: TCM syndrome integral scale
timeFrame: 4weeks,8weeks,12weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
Study officials:
affiliation: Beijing University of Chinese Medicine
name: Wei Wang, Doctor
role: STUDY_CHAIR
affiliation: Beijing University of Chinese Medicine
name: Huihui Zhao, Doctor
role: STUDY_DIRECTOR
affiliation: Beijing University of Chinese Medicine
name: Jinping Wang, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li X, Zhang J, Huang J, Ma A, Yang J, Li W, Wu Z, Yao C, Zhang Y, Yao W, Zhang B, Gao R; Efficacy and Safety of Qili Qiangxin Capsules for Chronic Heart Failure Study Group. A multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the effects of qili qiangxin capsules in patients with chronic heart failure. J Am Coll Cardiol. 2013 Sep 17;62(12):1065-1072. doi: 10.1016/j.jacc.2013.05.035. Epub 2013 Jun 7.
citation: General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent. 2014 Summer;81(3):14-8.
citation: Switula D. Principles of good clinical practice (GCP) in clinical research. Sci Eng Ethics. 2000 Jan;6(1):71-7. doi: 10.1007/s11948-000-0025-z.
citation: van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail. 2016 Mar;18(3):242-52. doi: 10.1002/ejhf.483. Epub 2016 Jan 4.
citation: Wang J, Shi J, Wei J, Wang J, Gao K, Li X, Chen J, Li S, Zhao H, Wang W. Safety and efficacy of Qishen granules in patients with chronic heart failure: study protocol for a randomized controlled trial. Trials. 2017 Oct 10;18(1):468. doi: 10.1186/s13063-017-2193-z.