Clinical trial NCT04944706: Efficacy and Safety of Qishenyiqi Dripping Pills for Treating Chronic Heart Failure With Preserved Ejection Fraction
Official title: Efficacy and Safety of Qishenyiqi Dripping Pills for Treating Chronic Heart Failure With Preserved Ejection Fraction: a Randomized, Double-blind, Basic-treatment-loading, Placebo-controlled, Multicenter Phase Ⅱ Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Heart Failure With Preserved Ejection Fraction
Lead sponsor: Tasly Pharmaceutical Group Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 225
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: Main objective: To evaluate the efficacy, safety and clinical dose exploration of Qishen Yiqi dripping pills in the treatment of chronic heart failure with preserved ejection fraction.

Detailed description: Main objective: To evaluate the efficacy, safety and clinical dose exploration of Qishen Yiqi dripping pills in the treatment of chronic heart failure with preserved ejection fraction.

Exploratory research objective: To explore the changes of endogenous substances in vivo before and after drug administration, to interpret the mechanism of drug action through metabolomics and systems biology methods, and to find potential clinical biomarkers for exploratory subgroup analysis of clinical trials.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects aged ≥ 18 years
* Diagnosed as chronic heart failure with preserved ejection fraction according to the Guidelines for Diagnosis and Treatment of Heart Failure in China 2018

  1. Have symptoms and/or signs of chronic heart failure at least 30 days before the trial
  2. LVEF≥50% according to echocardiography during screening stage
  3. BNP \> 35 ng/L and/or NT-proBNP \> 125 ng/L
  4. Cardiac structural changes or diastolic dysfunction according to echocardiography during screening stage, in line with at least one of the following:

     1. : LAVI\>34ml/m2
     2. : E/e'≥13
     3. : average e'(interventricular septum and free wall)\<9cm/s
* NYHAⅡ-Ⅲ
* Patients with hypertension received a stable dose of antihypertensive therapy for at least 4 weeks and kept their blood pressure at an ideal level for at least 4 weeks
* Ability to understand the requirements of the study and willingness to provide written informed consent
* Have no pregnancy program and take effective contraceptive measures voluntarily
* Abide by the experimental protocol and cooperate with the data collection according to the researcher's judgment

Exclusion Criteria:

* People with any of the following cardiovascular diseases:

  1. Patients with acute decompensated heart failure who need to use quick-acting diuretics, vasodilators, or positive inotropic drugs for treatment, or in the adjustment period of acute decompensated heart failure treatment, and the adjustment time is less than 1 month
  2. Clinical evidence of acute coronary syndrome (including myocardial infarction, unstable angina pectoris) within 6 months before screening stage
  3. Received prior revascularization (such as PCI, CABG), or implantable cardioverter defibrillator (ICD), or other cardiac/cardiovascular procedures within 3 months before screening stage
  4. Received cardiac resynchronization therapy (CRT) within 6 months before screening stage
  5. Implantable devices (e.g. ICD, CRT), revascularization (e.g. PCI, CABG), or other cardiac/cardiovascular procedures are expected to be performed during the trial period
  6. Patients with acute myocarditis, invasive cardiomyopathy, constrictive pericarditis, cardiac tamponade, hypertrophic obstructive cardiomyopathy, cardiac shock, hemodynamic abnormalities of heart valve disease significantly narrow and/or regurgitation (moderate or above, etc.), Ⅱ degrees above Ⅱ type atrioventricular block placement pacemaker therapy, average QTc \> 450 ms or heart rate \< 50 times/min
  7. Patients with pulmonary artery embolism caused by pulmonary hypertension, chronic obstructive pulmonary disease and other serious pulmonary diseases
  8. Hypertension that is difficult to control with medication (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg)
  9. Symptomatic hypotension and/or systolic blood pressure \<100 mmHg
* Severe renal insufficiency: eGFR \< 30 ml/min/1.73m2
* ALT and AST \> 3 times upper the limit of normal values in local laboratories, and/or total bilirubin \> 2 times upper the limit of normal values in local laboratories
* Serum potassium ≥5.5 mmol/L
* HbA1c≥9.0%, or fasting blood glucose \>13.9 mmol/L
* Diabetic patients who are using sodium-glucose cotransporter 2 inhibitors and cannot stop using them during the trial, such as dagliredin, entagliredin, and cagliredin
* The ECG examination indicated the onset of atrial fibrillation during the screening period or previous history of atrial fibrillation within 6 months before screening stage
* Hemoglobin \< 9.0 g/dL
* Patients have stroke 3 months before the screening period
* Concomitant mental illness and poor condition control, which affects the signing of informed consent or presentation of adverse events
* Patients with active malignancies (including those currently under oncology treatment)
* Unable to conduct the 6-minute walking distance test due to physical impairment or other non-cardiac reasons
* Women who are pregnant or lactating
* Allergic constitution, or allergic to the test drug or its ingredients
* Participate in clinical trials of other drugs within 3 months before screening
* The researchers did not consider it appropriate to participate in this study

Primary outcomes:
measure: 6-Minutes-Walking-Test (6MWT)
timeFrame: Baseline to weeks 12 and 24
Secondary outcomes:
measure: NT-proBNP
timeFrame: Baseline to weeks 2,4,8,12,16,20 and 24
measure: LAVI, E/ E ', E 'mean value, LVEF and tricuspid regurgitation velocity
timeFrame: Baseline to weeks 4,12 and 24
measure: Hospitalizations for heart failure (first or repeated) and deaths from cardiovascular disease
timeFrame: Week 24
measure: NYHA classification
timeFrame: Baseline to weeks 2,4,8,12,16,20 and 24
measure: Minnesota Living With Heart Failure Questionnaire(MLHFQ) Score
timeFrame: Baseline to weeks 12 and 24
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Bejing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Shijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Xinxiang
country: China
facility: The Third Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Changsha
country: China
facility: The third Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Changchun
country: China
facility: China Japan Union Hospital of Jilin University
state: Jilin
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Nei Monggol Autonomous Region
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital Of Xi'an Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Chest Hospital
state: Tianjin
Study officials:
References: