The Efficacy and Safety of Zhigancao Tang Granule for HFpEF of Qi-Yin Dificiency (HFpEF)

A Randomized，Double-blinded, Placebo-controlled Trial Evaluating the Efficacy and Safety of Zhigancao Tang Granule for HFpEF of Qi-Yin Dificiency

This study was designed as a randomized, double blinded and placebo-controlled clinical trial. The aim of the study is to evaluate the efficacy and safety of Zhigancao Tang granule in patients with HFpEF of Qi-Yin dificiency.

Study Overview

• Status: Unknown
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Zhigancao Tang granule; Drug: Zhigancao Tang placebo granule

Detailed Description

Heart failure with preserved ejection fraction (HFPEF) is a clinical syndrome characterized by diastolic dysfunction.The incidence of HFpEF is increasing in recent years. Standard treatment of heart failure does not improve the prognosis of HFPEF patients. Zhigancao Tang was used to improve the symptoms of chronic heart failure in China.This randomized,double-blinded and placebo-controlled trial will objectively and standardly evaluate the effectiveness and safety of Zhigancao Tang granule.After 12 weeks of treatment, 122 HFpEF patients with deficiency of Qi and Yin were observed and evaluated in terms of heart function, clinical symptoms,exercise tolerance and quality of life.

• Study Type: Interventional
• Enrollment (Anticipated): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Longhua Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Comply with the diagnostic criteria of Western medicine for HFpEF and the diagnostic criteria for TCM syndromes of Qi-Yin deficiency;
2. Cardiac function classification by NYHA: grade I to III;
3. Age between 30 and 80 years old;
4. Those who volunteer to participate in clinical trial observation, sign informed consent and indicate date;
5. During the observation period, those who do not take other drugs other than those specified and can insist on completing the treatment and observation.

Exclusion Criteria:

1. Valvular heart disease, restrictive cardiomyopathy, pericardial disease;
2. Decompensated heart failure is unstable after treatment;
3. Combined with atrial fibrillation;
4. Patients with severe lung, liver, endocrine system and kidney dysfunction;
5. Patients with cancer and other common malignant diseases reducing life expectancy;
6. Pregnant or lactating women;
7. Allergic constitution or allergic history to common drugs;
8. Patients with mental illness or poor compliance of traditional Chinese medicine treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zhigancao Tang granule group; Participants in experimental group will receive Zhigancao Tang granule therapy for 12 weeks. In addition, participants will receive standard heart failure treatment，including ACEI/ARB/ARNI, aldosterone antagonists, beta blockers, nitrate esters, diuretics as needed.	Drug: Zhigancao Tang granule; Zhigancao Tang: Dissolve Zhigancao Tang granule in 200ml hot water, twice a day,12 weeks, oral. Standard heart failure treatment，including ACEI/ARB/ARNI, aldosterone antagonists, beta blockers, nitrate esters and diuretics as needed.; Other Names: Zhigancao Tang group; Zhigancao Tang granule group
Placebo Comparator: Zhigancao Tang placebo group; Participants in experimental group will receive Zhigancao Tang placebo granule therapy for 12 weeks. In addition, participants will receive standard heart failure treatment，including ACEI/ARB/ARNI, aldosterone antagonists, beta blockers, nitrate esters and diuretics as needed.	Drug: Zhigancao Tang placebo granule; Zhigancao Tang placebo: Dissolve Zhigancao Tang placebo granule in 200ml hot water, twice a day,12 weeks, oral. Standard heart failure treatment，including ACEI/ARB/ARNI, aldosterone antagonists, beta blockers, nitrate esters and diuretics as needed.; Other Names: Zhigancao Tang placebo group; Zhigancao Tang placebo granule group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Functional Grading	Significant effect: cardiac function recovered to level 1 or increased by level 2; Effective: cardiac function increased by level 1 but failed to reach level 2; Ineffective: cardiac function did not change; Worsening: cardiac function decreased by level 1 or above.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasonic cardiogram	Echocardiographic measurement of Left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVESD), ratio of left ventricular early diastolic fast filling peak to late diastolic filling peak (E / a), ratio of early diastolic velocity of mitral valve to early diastolic annular velocity (E / E ').	12 weeks
6-min walking test (6mwt)	6 minute walking test (6mwt) is a measure of the distance the patient can reach as far as possible by walking on a hard ground without obstacles within six minutes at the fastest possible speed. It provides a comprehensive assessment of exercise capacity.	12 weeks
Minnesota Heart Failure Quality of Life Scale	Minnesota Heart Failure Quality of Life Scale was used to assess the impact of heart failure on life in the last four weeks. A total of 21 questions related to physical and emotional change. Higher scores mean a worse outcome.	12 weeks
N-terminal pro-B-type natriuretic peptide（NT-proBNP）	NT-proBNP is a reliable and sensitive indicator of heart failure. Its elevation is positively correlated with severity of heart failure.	12 weeks
TCM syndrome score	TCM syndrome score is used to assess changes in Qi-Yin Dificiency related symptoms during treatment. The higher the scores, the more heart failure symptoms. Higher scores mean a worse outcome.	12 weeks

Collaborators and Investigators

• Sponsor: Shanghai University of Traditional Chinese Medicine
• Investigators: Study Director: Bing Deng, M.D, Shanghai Longhua Hospital

Publications and helpful links

General Publications

• Zhang N, Zhao Y, Liu Y, Tang N, Zheng W, Mao M, Liu Q, Shen L, Deng B. A double-blinded, placebo-controlled randomized trial evaluating the efficacy and safety of Zhigancao Tang granules for treating HFpEF: study protocol for a randomized controlled trial. Trials. 2021 Apr 20;22(1):293. doi: 10.1186/s13063-021-05232-6.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 20, 2020
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 19, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: heart failure with preserved ejection fraction; Qi-Yin deficiency syndrome; randomized, double blinded and controlled trial; Zhigancao Tang granule
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ZGCT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No