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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03027375
• Other study ID #: 2016-ZXFZJJ-003
• Status: Recruiting
• Phase: Phase 2
• First received: January 16, 2017
• Last updated: October 6, 2017
• Start date: March 31, 2017
• Est. completion date: December 2018

Study information

• Verified date: October 2017
• Source: Beijing University of Chinese Medicine
• Contact: Jinping Wang, Master
• Phone: 13810689802
• Email: wjpbucm[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Heart Failure

Intervention

Drug:
• Qishen Granules
The QSG are manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China), a company that has obtained Chinese Good Manufacturing Practice for Pharmaceutical Products certification. All the ingredients have been approved by the Chinese Ministry of Food and Drug Safety. 13.6 grams (dry weight) of granules consist of six herbs: Astragalus membranaceus (Fisch.) Bge. var. Mongolicus (Bge.) Hsiao (6g), Salvia miltiorrhiza Bge. (1.5g), Lonicera japonica Thunb. (2g), Scrophularia ningpoensis Hemsl. (2g), Aconitum carmichaeli Debx. (0.9g), and Glycyrrhiza uralensis Fisch. (1.2g).
• Placebo
The placebo is manufactured by Beijing tcmages Pharmaceutical Co., Ltd. (Beijing, China) as well, following the Specification for processing Chinese medicine in Beijing. The placebo granules are similar in appearance, taste, and scent to the Qishen granules.

Locations

Country	Name	City	State
China	China-Japan Friendship Hospital	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Beijing University of Chinese Medicine	Beijing Anzhen Hospital, China-Japan Friendship Hospital, Zhengzhou Hospital of Traditional Chinese Medicine

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View 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):1065-72. doi: 10.1016/j.jacc.2013.05.035. Epub 2013 Jun 7. — View Citation

Switula D. Principles of good clinical practice (GCP) in clinical research. Sci Eng Ethics. 2000 Jan;6(1):71-7. — View 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: 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide		12weeks
Secondary	composite cardiac events		4weeks,8weeks,12weeks
Secondary	New York Heart Association (NYHA) functional classification		4weeks,8weeks,12weeks
Secondary	6-minute walking distance		4weeks,8weeks,12weeks
Secondary	Left ventricular ejection fraction		12weeks
Secondary	Chronic Heart Failure Quality of Life Scale of Integrated Chinese and Western Medicine		4weeks,8weeks,12weeks
Secondary	TCM syndrome integral scale		4weeks,8weeks,12weeks