Clinical trial NCT04498962: The Effect of Danzhu Fuyuan Granule as Adjunctive Therapy for Chronic Stable Angina, Vascular Dementia and Idiopathic Membranous Nephropathy: A Bayesian Basket Trial
Official title: The Effect of Danzhu Fuyuan Granule as Adjunctive Therapy for Chronic Stable Angina, Vascular Dementia and Idiopathic Membranous Nephropathy: A Bayesian Basket Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Stable Angina
Vascular Dementia
Idiopathic Membranous Nephropathy
Keywords: Danzhu Fuyuan Granule; Basket Trial
Lead sponsor: China Academy of Chinese Medical Sciences
Sponsor class: OTHER
First posted: 2020-08-05
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed as a bayesian basket trial , which aims to evaluate the efficacy of Danzhu Fuyuan Granule in patients with Chronic Stable Angina, Vascular Dementia and Idiopathic Membranous Nephropathy


Eligibility criteria: Eligibility Criteria for Chronic Stable Angina group

Inclusion criteria for Chronic Stable Angina group

1. Patient must be between the ages of 40 and 70 years
2. Evidence of coronary artery disease that consists of a well-documented medical history (over 3 months prior to the enrollment) of myocardial infarction or significant coronary artery disease with noninvasive or angiographic confirmation.
3. Patient must match the diagnostic criteria for chronic stable angina set by Chinese Medical Association;
4. The number of angina pectoris attacked in the past 3 months was more than 2 times per week
5. Class I or Class II, Grading of Angina Pectoris by the Canadian Cardiovascular Society Classification System
6. Patients who met the clinical diagnostic criteria for Syndrome of intermingled phlegm and blood stasis with chronic stable angina;
7. The results of Treadmill Exercise Test were positive;
8. All other Traditional Chinese Medicine interventions (including decoction, granule, proprietary Chinese medicine, acupuncture, etc.) should be stopped for 2 weeks or more;
9. They signed the consent form voluntarily and agreed to participate in the research.

Exclusion criteria for Chronic Stable Angina group

1. patients who are diagnosed with acute coronary syndrome (including acute myocardial infarction or unstable angina pectoris) occurred within 2 months before enrollment, or had undergone revascularization within 3 months before enrollment, or planned to undergo revascularization during the study period;
2. Patients who are unable to complete Treadmill Exercise Test for various reasons, including absolute and relative contraindications;
3. Severe primary diseases such as respiratory, blood system or malignant tumor, or known renal insufficiency (serum creatinine (CR) \> 221 umol /L in male, or 177 umol / L in female);
4. Patients with epilepsy who had bleeding tendency, history of cerebral hemorrhage, or needed anticonvulsant therapy;
5. Patients with active liver disease, or accompanied with unexplained continuous increase of serum transaminase, or the detection value of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is more than twice the upper limit of normal reference value;
6. Pregnancy or lactation;
7. patients can't stopped taking long-acting nitrates during the clinical trial;
8. undergoing other clinical trials;
9. There was a history of alcoholism or drug dependence in the past two years;
10. Other situations that the research physician thinks are not suitable to participate in this trial include but are not limited to: the subjects cannot follow the research protocol, which will bring potential safety hazards to the subjects, etc.

Eligibility Criteria for Vascular Dementia group

Inclusion criteria for Vascular Dementia group

1. The age of the subjects was 35-85 years old;
2. It was in accordance with the diagnostic standard of Western medicine for vascular dementia;
3. It is in accordance with the diagnostic standard of TCM phlegm and blood stasis syndrome of vascular dementia;
4. They signed informed consent and volunteered to participate in the study;
5. The patients are expected to follow up within half a year.

Exclusion criteria for vascular dementia group

1. Early memory impairment with progressive deterioration, early prominent features of Parkinson's disease, and primary nervous system diseases (such as multiple sclerosis, encephalitis, etc.);
2. There was no vascular lesion in neuroimaging examination;
3. Other diseases that can explain cognitive impairment, such as brain tumor, multiple sclerosis, encephalitis, depression, poisoning, and systemic diseases and metabolic abnormalities that significantly affect cognitive function;
4. Severe heart, brain, liver and hematopoiesis diseases, or other serious diseases affecting their survival;
5. Drug or alcohol abuse / dependence within 3 months before participating in the trial;
6. Pregnant and lactating women;
7. Patients with severe mental disorders (perception disorders, thinking disorders);
8. For known renal insufficiency, serum creatinine (CR) was higher than 221 umol/L in male and 177 umol/L in female;
9. Patients with known liver dysfunction, alanine aminotransferase (ALT) \> 3 times of normal value or with cirrhosis;
10. The researchers believe that there are other situations that are not suitable for participating in this study.

Eligibility Criteria for Idiopathic Membranous Nephropathy group

Inclusion criteria for Idiopathic Membranous Nephropathy group

1. The pathological diagnosis of renal biopsy was membranous nephropathy;
2. The syndrome of TCM is phlegm and blood stasis;
3. The urinary protein was more than 1G / D and \< 8g / d;
4. Blood pressure can be effectively controlled at ≤ 140 / 90mmHg;
5. eGFR≥45ml/min；
6. The age ranged from 18 to 70 years old;
7. Sign informed consent.

Exclusion criteria for Idiopathic Membranous Nephropathy group

1. All kinds of secondary membranous nephropathy;
2. Those who are taking hormone and / or immunosuppressive therapy;
3. Women with pregnancy planning, pregnancy and lactation;
4. Severe heart, brain, liver and hematopoiesis diseases, or other serious diseases affecting their survival;
5. Participants in other clinical trials in recent 3 months.

Primary outcomes:
measure: Primary endpoint 1 for Chronic Stable Angina Group: the time to ST depression at the end of week 8 compared with baseline on submaximal exercise Modified Bruce Protocol
timeFrame: 8 weeks
measure: Primary endpoint 2 for Chronic Stable Angina group: the score on Syndrome Questionnaire of Intermingled Phlegm and Blood Stasis with Chronic Stable Angina at the end of week 8 compared with baseline
timeFrame: 8 weeks
measure: Primary endpoint 1 for Vascular Dementia group: the score of Mini-mental State Examination at the end of month 6 compared with baseline
timeFrame: 6 month
measure: Primary endpoint 2 for Vascular Dementia group: the score on Syndrome Questionnaire of Intermingled Phlegm and Blood Stasis with Vascular Dementia at the end of month 6 compared with baseline
timeFrame: 6 month
measure: Primary endpoint 1 for Idiopathic Membranous Nephropathy group: level of the 24 hour urine protein quantification at the end of month 6 compared with baseline
timeFrame: 6 months
measure: Primary endpoint 2 for Idiopathic Membranous Nephropathy group: the score on Syndrome Questionnaire of Intermingled Phlegm and Blood Stasis with Idiopathic Membranous Nephropathy at the end of month 6 compared with baseline
timeFrame: 6 months
Secondary outcomes:
measure: Duke treadmill score (DTS) at the end of week 8 compared with baseline on submaximal exercise Modified Bruce Protocol
timeFrame: 8 weeks
measure: the score on Seattle Angina Questionnaire
timeFrame: 8 weeks
measure: Frequency of weekly angina episodes
timeFrame: 8 weeks
measure: Angina pectoris severity classification according to Canadian Cardiovascular Society (CCS)
timeFrame: 8 weeks
measure: Stopping or reducing rate of the Nitroglycerin Table
timeFrame: 8 weeks
measure: Number of subjects with adverse events or severe adverse events
timeFrame: 8 weeks
measure: Brain pulse index mearsured by Transcranial Doppler
timeFrame: 6 months
measure: Arterial systolic blood flow velocity mearsured by Transcranial Doppler
timeFrame: 6 months
measure: Mean flow velocity mearsured by Transcranial Doppler
timeFrame: 6 months
measure: Level of serum creatinine
timeFrame: 6 months
measure: Level of blood urea nitrogen
timeFrame: 6 months
measure: Glomerular filtration rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xiyuan hospital， China Academy of Chinese Medical Sciences
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial People's Hospital
state: Fujian
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Henan University of traditional Chinese Medicine
state: Henan
city: Wuhan
country: China
facility: Hubei Provincial Hospital of Traditional Chinese Medicine
state: Hubei
city: Wuhan
country: China
facility: Yichang Hospital of Traditional Chinese Medicine
state: Hubei
city: Nanchang
country: China
facility: Affiliated Hospital of Jiangxi University of traditional Chinese Medicine
state: Jiangxi
city: Tianjin
country: China
facility: The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
state: Tianjin
Study officials:
References: