A Phase IIa Clinical Trial on TSG-01 in the Treatment of Chronic Heart Failure in Patients With Coronary Heart Disease.

Chronic Heart Failure Clinical Trial

Official title:

A Phase IIa Clinical Trial on TSG-01 in the Treatment of Chronic Heart Failure in Patients With Coronary Heart Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04515290
• Other study ID #: HYT-CT-01
• Status: Completed
• Phase: Phase 2
• Start date: May 7, 2020
• Est. completion date: April 22, 2022

Study information

• Verified date: October 2022
• Source: Shanghai Hongyitang Biopharmaceutical Technology Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, efficacy and optimal dose of TSG-01, an innovative drug with ginsenosides as its main components, in the treatment of patients with chronic heart failure(CHF). Preclinical studies have revealed that TSG-01 promote myocardial energy metabolism and ATP production, reduce the damage of human pulmonary microvascular endothelial cell connection, resist arrhythmia, and regulate the lipid metabolism disorder caused by myocardial ischemia. Results from CHF animal models(dog, rat) showed that TSG-01 significantly increase coronary blood supply, improve myocardial contractility, reduce heart expansion and pulmonary edema. Besides its potency of improving heart function, TSG-01 was found to induce diuresis without obvious effect on urine potassium in rats. TSG-01 has been approved by CFDA for a clinical trial on the treatment of CHF (Approval No. 2018L03012). A randomized, double-blind, multicenter, placebo-controlled phase IIa clinical trial is now being conducted in 5 hospitals in China. A total of 90 cases of CHF caused by coronary heart disease are included and randomly divided into three groups: high-dose, low-dose of TSG-01 and placebo group. NYHA functional class, 6-minute walk test(6MHWT) distance, NT-proBNP, left ventricular ejection fraction(LVEF), echocardiographic parameters (LVESV, LVEDV, and heart size) and MLHFQ score are measured before, during and after treatment to evaluate the benefits of TSG-01 therapy in patients with CHF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: April 22, 2022
• Est. primary completion date: April 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age: 40 to 75 years.

• Have chronic heart failure(CHF) due to ischemic causes and defined as NYHA classification of III.

• Left ventricular ejection fraction (LVEF) of =45% and =25% as determined by improved biplane Simpson method

• NT-proBNP=450pg/ml

• Be on a stable regime of standardized therapy for CHF at least 2 weeks prior to receiving study medication and are respected to remain on a stable regime throughout the duration of the trial without the need to receive intravenously vasoactive agents or/and diuretics. Standardized therapy includes ACEI/ARB, beta-blocker, aldosterone receptor antagonist, diuretic, digitalis.

• Is able to understand the trial and provide informed consent.

Exclusion Criteria:

• Has hypertensive cardiopathy, pulmonary heart disease, congenital heart disease, moderate to severe pulmonary hypertension (pulmonary artery pressure = 40mmHg), moderate to severe cardiac valve stenosis or insufficiency, any type of cardiomyopathy(hypertrophic, restrictive or dilated cardiomyopathy); moderate to severe pericardial effusion, constrictive pericarditis, and heart failure caused by arrhythmia.

• Has noncardiogenic heart failure caused by diseases in kidney, lung, liver, or by rheumatic immune disorders, severe infection and chemical factors (chemotherapy, alcohol, etc.).

• Has active tuberculosis or systemic lupus erythematosus (SLE)

• Had acute myocardial infarction, biventricular pacemaker implantation for cardiac resynchronization, cardiothoracic surgery or was complicated with acute coronary syndrome, pulmonary embolism and acute cerebrovascular disease within 3 months prior to receiving study medication.

• Had symptomatic ventricular tachycardia or pleomorphic ventricular tachycardia, cardiogenic shock (CGS), a progressive exacerbation of unstable angina, uncontrolled malignant arrhythmia, second degree sinoatrial or AV block Mobitz Type II or above without pacemaker implantation, QTc>550 ms and heart rate <50 bmp. Had uncontrolled hypertension, systolic blood pressure=180/mmHg and/or diastolic blood pressure=110mmHg, or hypotension with systolic blood pressure<90mmHg and/or diastolic blood pressure<60mmHg.

• Had coronary revascularization procedure (percutaneous or surgical) within 12 weeks prior to receiving study medication or be expected to have coronary revascularization or left ventricular remodeling operation in next 12 weeks.

• Has hepatic abnormality defined as ALT=1.5 times the upper limit of normal, or has impaired renal function with Cr=1.5 times the upper limit of normal. Has severe anemia (Hb<70g/L), pheochromocytoma, hematopathy, gastrointestinal bleeding (consecutive fecal occult blood tests positive, except bleeding caused by hemorrhoids or other anal diseases).

• Has a body weight>200kg.

• The subject has the need for mechanical ventilation, or has a history of a stroke or any malignancy within 4 weeks prior to receiving study medication.

• Has psychosis with poor control, or is a drug addict who has not been detoxified.

• Allergic to the study drug.

• Has participated in any clinical trial involving experimental therapy 3 months prior to screening.

• If female, being pregnant or lactating, or plan to get pregnant in next 3 months.

• Has a survival time less than 3 months according to the investigator's judgement.

• Subject who are taking Entresto (Sacubitril Valsartan Sodium Tablets) medication.

• Unable to complete the study or comply with the requirements of the study (for management or other reasons) according to the investigator's judgement.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Heart Failure
• Myocardial Ischemia

Intervention

Drug:
• TSG-01
Two tablets of TSG-01 (0.35g/tablet) were given by oral with 3 times a day for 12 weeks; High dose group.
• TSG-01 and Placebo
One tablet of TSG-01 (0.35g/tablet) and one tablet of placebo (0.35g/tablet) were given by oral with 3 times a day for 12 weeks; Low dose group.
• Placebo
Two tablets of placebo (0.35g/tablet) were given by oral with 3 times a day for 12 weeks.

Locations

Country	Name	City	State
China	Zhejiang Provincial Hospital of Chinese Medicine	Hangzhou	Zhejiang
China	Affiliated Hospital of Nanjing University of Chinese Medicine	Nanjing	Jiangsu
China	Shanghai Shuguang Hospital	Shanghai	Shanghai
China	Henan Province Hospital of TCM	Zhengzhou	Henan
China	The first Affiliated Hospital of Henan University of CM	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Hongyitang Biopharmaceutical Technology Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	New York Heart Association (NYHA) Classification	Change from baseline and placebo in NYHA class status. NYHA Classification is a heart function classification which divides impaired cardiac function into four levels according to the action capacity of the patient. And among NYHA classification, Class I represents the mildest symptoms, while Class IV represents the most severe case.	12th week after intervention
Primary	Six(6)-minute walk test	To measure the distance that the patient is instructed to walk along a hallway as far as he(or she) can in 6 minutes.	12th week after intervention
Secondary	Change of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) Level from baseline and placebo		12th week after intervention
Secondary	Change in LVEF from screening/baseline as determined by echocardiography		12th week after intervention
Secondary	Change in LVESV from screening/baseline as determined by echocardiography		12th week after intervention
Secondary	Change in LVEDV from screening/baseline as determined by echocardiography		12th week after intervention
Secondary	Change in cardiac size from screening/baseline as determined by echocardiography		12th week after intervention
Secondary	Minnesota Living with Heart Failure Questionnaire (MLHFQ)		12th week after intervention