Clinical trial NCT04028544: The Study of Qishenyiqi Drop Pills in Improving the Prognosis of Heart Failure Patients
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Qishenyiqi Drop Pills in Improving the Prognosis of Heart Failure Patients With Reduced Ejection Infarction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure
Keywords: heart failure
traditional Chinese medicine
prognosis
Qishenyiqi
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
Collaborators: name: Tianjin Tasly Pharmaceutical Co., Ltd
First posted: 2019-07-22
Enrollment: 5380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled study including patients with ejection fraction decreased heart failure under standardized treatment, to evaluate QiShenYiQi (QSYQ) dropping pill's curative effect in reducing cardiovascular death and heart failure rehospitalization compared with placebo.

Detailed description: This is a prospective, large-scale samples, randomized, double-blind, placebo parallel-controlled, multicenter study to evaluate QSYQ's curative effect in reducing cardiovascular death and heart failure rehospitalization in patients with ejection fraction decreased heart failure（LVEF≤40%）under standardized treatment. The results will provide clinical evidence for combined treatment of traditional Chinese medicine and western medicine in ejection fraction decreased heart failure.

There are two treatment groups in the study, which are the treatment group with standard treatment + QSYS (oral use, 1 bag each time, three times a day) , and the control group with standard treatment + placebo (oral use, 1 bag each time, three times a day) .

The subjects are patients with ejection fraction decreased (≤40%) heart failure (NYHA II-IV). The sample size is 5380. For the primary end event, type I error is bilateral 0.05, and POWER was 0.8. The CV death and the HF readmission rate in the trial control group is 15%, and 12.7% in the experimental group. The trial cycle is about 3 years. A total of 4373 subjects will be assigned to the experimental group and the control group at a proportion of 1:1. The primary endpoint was expected to be 1211 cases. Taking into account the annual rate of lost to follow-up is about 18%, the final sample cases is 5380. During the treatment period and extends to at most 2weeks after treatment, patients will get examination including interviews (direct inquiries about the occurrence of adverse events and the situation of taking drugs), physical examination, body weight and the ECG. Laboratory parameters to evaluate clinical safety, such as routine blood, serum creatinine and urea nitrogen, electrolyte (serum potassium, sodium and chloride) and liver enzymes will be taken regularly. Researchers need to record and evaluate any occurrence of adverse events (AE) or serious adverse event (SAE) and its relevance to study medicine.

The primary endpoint is to evaluate whether QSYQ can reduce cardiovascular death and heart failure rehospitalization in chronic heart failure patients with reduced ejection infarction (HFREF) compared with placebo.

Eligibility criteria: Inclusion Criteria:

* Ability to understand the requirements of the study and willingness to provide written informed consent.
* Male or female subjects aged ≥ 18 years
* Patients with ejection fraction decreased heart failure (NYHA II-IV, Echocardiography with Simpson method within four weeks and NT-proBNP within two weeks before random) （1）35%≤LVEF≤40% ; NT-proBNP≥900pg/ml, patients with renal dysfunction (glomerular filtration rate \<60 ml/min/1.73m2）or atrial fibrillation, the NT-proBNP should be ≥1200 pg/ml； （2）LVEF\<35% (Simpson method); NT-proBNP≥600pg/ml, patients with renal dysfunction (glomerular filtration rate \<60 ml/min/1.73m2）or atrial fibrillation, the NT-proBNP should be ≥900 pg/ml.
* A history of hospitalization or emergency treatment for heart failure in the past two years and a diagnosis of heart failure at least one month ago
* The use of medications in line with the recommendation of China heart failure treatment guidelines for at least 4 weeks. (Please confirm that all the following conditions must be met) : Including a ACEI or ARB, and a beta- blocker, unless contraindicated or not tolerated. The doses should reach the target dose recommended by the guideline or the maximum dose that the patient can tolerate, and the doses should not be changed within one months prior to screening and randomization (patients not take such drugs according to the guidelines, should be recorded).

Exclusion Criteria:

* Acute decompensated HF with hemodynamic instability, mechanical hemodynamic support or invasive mechanical ventilation within 14 days of randomization, using intravenous positive inotropic drugs, vasoactive drugs and intravenous diuretics within 7 days before randomization.
* Poorly controlled hypertension, defined as resting systolic blood pressure≥180mmHg and /or diastolic blood pressure ≥110mmHg assessed on two separate occasions prior to randomization.
* Liver transaminase (ALT or AST), bilirubin more than 3 times the upper limit of normal not caused by heart failure, glomerular filtration rate\<15ml/min/1.73m2.
* Hemoglobin concentration ≤ 9.0g/dl and/or have blood system disease.
* Valvular heart disease, congenital heart disease without surgery.
* Cardiac shock.
* Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, other secondary and invasive cardiomyopathy.
* Active myocarditis.
* Constrictive pericarditis, other pericardial diseases.
* Syncope within 3 months.
* Symptomatic bradycardia or II or III degrees heart block without a pacemaker.
* Ventricular arrhythmias affecting hemodynamics.
* Cardiac resynchronization therapy implanted pacemaker (CRT-P) or cardiac resynchronization therapy defibrillators (CRT-D) within 6 months, or upgrade the existing conventional pacemaker or implantable implantable defibrillator (ICD) to the CRT device, or have the intention to implant similar devices.
* Occurred within 3 months: acute coronary syndrome, stroke, transient ischemic attack; Heart, carotid artery or other large vascular surgery; Percutaneous coronary intervention (PCI) or carotid artery angioplasty, CABG or other cardiac surgery.
* Major surgery within 6 months prior to randomization.
* Has a history of heart transplantation or are waiting for transplants or using left ventricular assist device (LVAD) or have intention to heart transplant (waiting for transplants) or implant the VAD.
* Severe chronic obstructive pulmonary disease, pulmonary heart disease, sever pulmonary vascular disease, pulmonary hypertension caused by autoimmune disease, any type of severe pulmonary hypertension.
* History of major organ transplant (such as lung, liver, heart, bone marrow, kidney).
* Patients with serious primary diseases of liver, kidney, hematopoietic system, nervous system, endocrine system, and patients with cancer or mental illness.
* Life expectancy is less than 1 year.
* Known allergy to any study drug.
* Participants in other clinical studies within 1 month.
* Patients who are taking Chinese medicine and proprietary Chinese medicine with similar ingredients of QSYQ.
* Women who have developed pregnancy (pregnancy test positive) or during lactation; women of childbearing age have not taken adequate contraceptive measures.
* According to the researchers, patients could not complete the study or fail to comply with the requirements of the study (due to management or other reasons).

Primary outcomes:
measure: Time to the occurrence of cardiovascular (CV) death or heart failure (HF) re-hospitalization.
timeFrame: up to 30 months
Secondary outcomes:
measure: Time to the occurrence of all-cause death.
timeFrame: up to 30 months
measure: Time to the occurrence of all-cause death or HF re-hospitalization.
timeFrame: up to 30 months
measure: Time to the occurrence of CV death.
timeFrame: up to 30 months
measure: Time to the occurrence of total HF re-hospitalization.
timeFrame: up to 30 months
measure: Time to the occurrence of composite endpoint.
timeFrame: up to 30 months
measure: Time to the first occurrence of HF hospitalization.
timeFrame: up to 30 months
measure: Change from baseline to week 48 for the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score.
timeFrame: from baseline to week 48
measure: Change from baseline to week 48 for the 6 minutes walking distance.
timeFrame: from baseline to week 48
Other outcomes:
measure: Time to the occurrence of HF death.
timeFrame: up to 30 months
measure: Time to the occurrence of total re-hospitalization for nonfatal myocardial infarction and nonfatal stroke.
timeFrame: up to 30 months
measure: The improvement of Kansas City Cardiomyopathy Questionnaire (KCCQ) score and sub-domain score.
timeFrame: up to 30 months
measure: Level of NT-proBNP in patients with HFrEF
timeFrame: from baseline to week 24 and week 48
measure: Value of LVEF in patients with HFrEF
timeFrame: from baseline to week 48
measure: Level of BNP in patients with HFrEF.
timeFrame: from baseline to week 48
measure: Value of clinical comprehensive score in patients with HFrEF.
timeFrame: from baseline to week 48
measure: Effectiveness in reducing medical cost and increasing Quality-adjusted life year （QALYs）in patients with HFrEF.
timeFrame: up to 30 months
Locations:
city: Beijing
country: China
facility: Fuwai Hospital
state: Beijing
Study officials:
affiliation: Heart Failure Center, Fuwai Hospital
name: Jian Zhang, MD
role: STUDY_CHAIR
References: