Coronary Microvascular DiseasePhase 4MAIDNCT07885462
Coronary MicrovAscular Diseases Intervention With Compound Danshen Dropping Pills
A Phase 4 study testing Compound Danshen Dripping Pills in people with Coronary Microvascular Disease, run by Qilu Hospital of Shandong University at 1 site in China.
Trial summary
Objective: To investigate the effect of Compound Danshen Dripping Pills （CDDP）on improving coronary flow reserve（CFR） in patients with coronary microvascular disease (CMVD) and to evaluate their efficacy and safety. Study Design: Randomized, double-blind, placebo-controlled, multicenter clinical trial. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Microvascular Disease
- What is being tested?
- Compound Danshen Dripping Pills
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 496 participants
- Where
- 1 siteChina
- Study dates
- Oct 2026to Dec 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants aged 18 to 80 years (inclusive).
- Within 6 months prior to randomization, coronary computed tomography angiography(CTA) or angiography demonstrating coronary stenosis ≤50%, or residual stenosis ≤50% after revascularization, or stenosis >50% with FFR >0.8.
- CFR of the left anterior descending（LAD） artery measured by transthoracic Doppler echocardiography（TTE） <2.5.
- Clinical diagnosis of CMVD, meeting any one of the following categories:
- （1）Ischemia-related CMVD:
- Myocardial Ischemia with Non-Obstructive Coronary Arteries: Presence of symptoms consistent with chronic myocardial ischemia, together with objective evidence of reduced CFR and/or coronary microvascular spasm, in the absence of obstructive epicardial coronary artery disease.
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- ②Myocardial Ischemia with obstructive Coronary Arteries: Following successful treatment of epicardial coronary artery stenosis with residual luminal stenosis ≤50%, TTE demonstrates persistent impairment of CFR <2.5 in the LAD.
- （2）Myocardial infarction-related CMVD:
- Myocardial infarction with non-obstructive coronary arteries (MINOCA): Coronary CTA or invasive coronary angiography demonstrates coronary artery stenosis ≤50%.
- Myocardial infarction with obstructive coronary arteries (MIOCA): Typically associated with coronary microvascular obstruction, including but not limited to ST-segment elevation myocardial infarction (STEMI) complicated by coronary microvascular obstruction.
- 5.Voluntary provision of written informed consent by the subject or legal representative.
Who cannot join
- Persistent or permanent atrial fibrillation; clinically significant bradyarrhythmias (including severe sinus bradycardia or second-degree type II or higher atrioventricular block); sinus node dysfunction; uncontrolled chronic obstructive pulmonary disease (COPD); or uncontrolled bronchial asthma.
- Severe valvular heart disease, cardiomyopathy, LVEF <50%, Takayasu arteritis, or aortic dissection.
- Acute myocardial infarction within 1 month prior to randomization.
- Unstable angina within 1 week prior to randomization.
- Hemorrhagic stroke within the previous 6 months.
- Uncontrolled hypertension, defined as systolic blood pressure (SBP) >150 mmHg and/or diastolic blood pressure (DBP) >90 mmHg despite appropriate medical management.
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- Hepatic dysfunction (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >2 ×ULN) or renal impairment (estimated glomerular filtration rate [eGFR] ≤60 mL/min/1.73m²).
- Pregnant, planning pregnancy, or breastfeeding.
- Clinically significant respiratory, gastrointestinal, hematologic, infectious, immunologic, endocrine, neurological, psychiatric, or malignant diseases that, in the investigator's judgment, may pose an unacceptable risk to the participant or interfere with study participation.
- Current requirement for anticoagulation therapy with warfarin; current use of nicorandil; or concomitant treatment with other traditional Chinese medicine (TCM) preparations.
- Active bleeding or clinically significant bleeding tendency, including platelet count <50×10⁹/L or documented coagulation disorders.
- Known or suspected hypersensitivity to intra-arterial contrast media, blood or blood products, or the investigational medicinal product.
- Participation in another interventional clinical trial within 3 months prior to randomization or concurrent participation in another clinical study.
- Any other medical condition or circumstance that, in the opinion of the investigator, would make the participant unsuitable for enrollment in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Qilu Hospital of Shandong University
Jinan, Shandong, 250000
Xiaoling Liu, MD, 86-18560086718, xiaolingliusdu@163.com
Yun Zhang, MD,PhD
About this study
Official title: Coronary MicrovAscular Diseases Intervention With Compound Danshen Dropping Pills(MAID)
Objective: To investigate the effect of Compound Danshen Dripping Pills （CDDP）on improving coronary flow reserve（CFR） in patients with coronary microvascular disease (CMVD) and to evaluate their efficacy and safety.
Study Design: Randomized, double-blind, placebo-controlled, multicenter clinical trial.
Read more
Study population: Patients with ischemia-related CMVD and myocardial infarction-related CMVD.
Intervention：Treatment group：standard therapy plus CDDP, Twenty pills (27 mg each) orally, three times daily after meals.Control group：standard therapy plus matching placebo, Twenty pills (27 mg each) orally, three times daily after meals.Treatment duration 12 months.
Primary Endpoint: Change in CFRmax from baseline to Month 12 (ΔCFRmax-12m) by Transthoracic Doppler echocardiography(TTE).
Read the detailed description
Rationale for the Study：Coronary Microvascular Disease (CMVD) is a clinical syndrome manifested as effort-induced angina pectoris or laboratory evidence of myocardial ischemia, which results from structural and/or functional abnormalities of the coronary pre-arterioles and arterioles under the effects of multiple pathogenic factors. Impaired coronary microcirculatory function is closely associated with long-term clinical outcomes in patients. A reduced coronary flow reserve (CFR) is not only associated with persistent angina, decreased exercise tolerance, and impaired quality of life, but also independently predicts the risk of cardiovascular death, non-fatal myocardial infarction, heart failure hospitalization, and major adverse cardiovascular events (MACE).Current domestic and international guidelines recommend risk factor control and anti-ischemic therapy as the foundational treatment for CMVD. However, the pathogenesis of CMVD is complex, involving multiple pathological processes such as endothelial dysfunction, microvascular spasm, microvascular remodeling, and inflammation. There is considerable heterogeneity in the treatment benefits among different patients, and evidence-based therapeutic strategies that can definitively improve coronary microcirculatory function and delay disease progression are still lacking.
Basic and clinical studies have demonstrated that the Chinese medicinal compound Compound Danshen Dripping Pills (CDDP) can improve vascular endothelial function and relieve angina pectoris, and it has been widely applied in clinical practice. In the preliminary study entitled Clinical Study on the Effect of Compound Danshen Dripping Pills on Coronary Flow Reserve in Patients with Coronary Microvascular Angina, CDDP effectively improved coronary flow reserve in patients with CMVD. These findings support the value of conducting larger-scale clinical studies to explore its clinical efficacy for CMVD, symptom improvement, and effects measured by the Seattle Angina Questionnaire.
Objective: To investigate the effect of Compound Danshen Dripping Pills （CDDP）on improving coronary flow reserve（CFR） in patients with coronary microvascular disease (CMVD) and to evaluate their efficacy and safety.
Hypothesis: In patients with CMVD receiving standard anti-ischemic therapy, treatment with CDDP for 12 months will significantly improve CFR, reduce major adverse cardiovascular events（MACE）, and improve quality of life compared with placebo.
This study adopts a stratified-block randomization design. A total of 496 study participants were divided into two subgroups according to disease diagnosis (Subgroup A: Ischemia-related CMVD; Subgroup B: Myocardial infarction-related CMVD, 248 participants in each subgroup). After the classification of participants into disease-specific subgroups, the system automatically activated the block allocation module corresponding to each subgroup. Participants were assigned to pre-defined groups sequentially according to the real-time enrollment order until the full quota of the subgroup was fulfilled.
During the study, a total of 5 visits will be conducted (Baseline/Screening, Month 3, Month 6, Month 9, and Month 12). At each visit, clinical data will be collected, along with an electrocardiogram (ECG), Canadian Cardiovascular Society (CCS) angina grading, and Seattle Angina Questionnaire (SAQ) scoring. Laboratory tests and echocardiography (including CFR assessment) will be performed at Baseline/Screening, Month 6, and Month 12.
Blood Sampling Protocol: Fasting venous blood samples will be collected at the clinical laboratory of Qilu Hospital of Shandong University on the mornings of the Baseline, Month 6, and Month 12 visits. A total of 3 samples will be collected, with 10 mL drawn each time (total volume: 30 mL). All samples will be sent to the clinical laboratory of Qilu Hospital of Shandong University.
Laboratory Assessments: The blood samples will first be used for routine clinical laboratory tests, including complete blood count (CBC), urinalysis, liver function (ALT, AST), renal function (serum creatinine, urea/BUN), coagulation panel (PT, APTT, TT, FIB), lipid profile (TC, TG, LDL-C, HDL-C), and myocardial enzymes (troponin T [TnT], creatine kinase [CK]). The remaining samples will be utilized for exploratory assessments, such as the detection of inflammatory and endothelial biomarkers, as well as omics screening. Any residual blood samples after the aforementioned tests will be stored uniformly in the cardiovascular laboratory for further exploratory testing in the future.
This study is a large-sample RCT clinical trial targeting CMVD, and is expected to provide evidence-based medical evidence for the treatment of CMVD.
- Conditions
- Coronary Microvascular Disease
- Being tested
- Compound Danshen Dripping Pills, Placebo
- Keywords
- Coronary Flow Reserve, Major adverse cardiovascular events, Seattle Angina Questionnaire, Canadian Cardiovascular Society Angina Class
- Medical subject headings
- Microvascular Angina
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Compound Danshen Dripping PillsDrug
Also called CDDP, Fufang Danshen Diwan, Cardiotonic Pill, Dantonic Pill
20 pills (540 mg) orally three times daily for 12 months. Each pill weighs 27 mg, containing Radix Salviae miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum. Manufactured and supplied by Tasly Pharmaceutical Group Co., Ltd.
PlaceboDrug
Also called Matching placebo
Placebo pills identical to Compound Danshen Dripping Pills in appearance, taste, and packaging, 20 pills orally three times daily for 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Conventional treatment + Compound Danshen Dripping Pills 540 mg | Experimental | Participants receive conventional treatment plus Compound Danshen Dripping Pills (CDDP), 20 pills (540 mg) orally three times daily for 12 months. Receives: Drug: Compound Danshen Dripping Pills |
| Conventional treatment + matching placebo | Placebo comparator | Participants receive conventional treatment plus placebo pills matching CDDP in appearance, 20 pills orally three times daily for 12 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in peak coronary flow reserve (CFRmax) of the left anterior descending artery
CFRmax is defined as the ratio of hyperemic to basal peak diastolic flow velocity (PDV) in the mid-to-distal left anterior descending artery, measured by transthoracic Doppler echocardiography (TTDE) during regadenoson-induced maximal hyperemia (regadenoson 0.4 mg/5 mL administered as a single intravenous bolus over approximately 10 seconds, followed by a saline flush). Measurements are performed at baseline, 6 months, and 12 months. Change from baseline at each time point is calculated as the value at that time point minus the baseline value. The primary analysis time point is 12 months.
Measured: Baseline, 6 months, and 12 months
Secondary outcomes (4)
Change from baseline in mean coronary flow reserve (CFRmean) of the left anterior descending artery
CFRmean is defined as the ratio of hyperemic to basal mean diastolic flow velocity (MDV) in the mid-to-distal left anterior descending artery, measured by transthoracic Doppler echocardiography (TTDE) during regadenoson-induced maximal hyperemia (regadenoson 0.4 mg/5 mL administered as a single intravenous bolus over approximately 10 seconds, followed by a saline flush). Measurements are performed at baseline, 6 months, and 12 months. Change from baseline at each time point is calculated as the value at that time point minus the baseline value.
Measured: Baseline, 6 months, and 12 months
Change from baseline in Seattle Angina Questionnaire (SAQ) score
The Seattle Angina Questionnaire (SAQ) is a disease-specific health status measure for coronary artery disease. Each of its five domains (Physical Limitation, Anginal Stability, Anginal Frequency, Treatment Satisfaction, and Disease Perception/Quality of Life) is scored from 0 to 100, with higher scores indicating better health status (fewer symptoms/limitations). Change from baseline is calculated as the score at each time point minus the baseline score.
Measured: Baseline, 3, 6, 9, and 12 months
Change from baseline in CCS angina class
Angina severity is classified by the Canadian Cardiovascular Society (CCS) angina classification, ranging from Class I (angina only during strenuous exertion; least severe) to Class IV (angina at rest; most severe), where a higher class indicates a worse outcome. Improvement is defined as a reduction of ≥1 CCS class grade from baseline at each assessment time point.
Measured: Baseline, 3, 6, 9, and 12 months
Incidence of major adverse cardiovascular events (MACE) within 12 months
MACE is a composite endpoint defined as the occurrence of any of the following components during the 12-month follow-up period: (1) cardiovascular death; (2) non-fatal myocardial infarction; (3) hospitalization for angina pectoris; and (4) hospitalization for heart failure.
Measured: From randomization/enrollment through 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Coronary Microvascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled, multicenter clinical trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 496 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qilu Hospital of Shandong University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhang Yun, Qilu Hospital of Shandong University
- Investigators
- Yun Zhang, MD,PhD, Principal investigator, Department of Cardiology,Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07885462
- Sponsor's protocol ID
- KYLL-2026-04(XZ)-004-2
- Acronym
- MAID
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared. The informed consent form approved by the ethics committee and signed by participants did not include provisions for sharing de-identified individual participant data beyond the research team or with external investigators, and additional consent for data sharing was not obtained at the time of enrollment.
Publications
Zhang PF, Tian JW, Zhu TG, Wu JF, Leng XP, Wang Y, Li MM, Li XH, Wang QQ, Feng XP, Lv JY, Yin LX, Zhang Y, Zhang M; Chinese Society of Echocardiography; Superficial Tissue and Vascular Group of Chinese Society of Ultrasound in Medicine; Ultrasound Professional Committee of Chinese Medicine Education Association. Stress Echocardiography for Chronic Coronary Syndrome: Clinical Practice Guidelines (2023). J Geriatr Cardiol. 2024 May 28;21(5):475-505. doi: 10.26599/1671-5411.2024.05.001. No abstract available.
PubMed 38948890Zhang Mei, Dai Xiaohua, Zhang Yun. Current status of basic research and clinical application of intracoronary Doppler ultrasound. Foreign Medical Sciences (Fascicle of Cardiovascular Disease). 1997, 24(5): 28-31.
Chinese Society of Cardiology, Chinese Medical Association. Chinese Expert Consensus on the Diagnosis and Treatment of Coronary Microvascular Disease (2023 Edition). Chinese Journal of Cardiology. 2024, 52(05): 460-492
Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010 Jun 22;55(25):2825-32. doi: 10.1016/j.jacc.2010.01.054.
PubMed 20579539Mileva N, Nagumo S, Mizukami T, Sonck J, Berry C, Gallinoro E, Monizzi G, Candreva A, Munhoz D, Vassilev D, Penicka M, Barbato E, De Bruyne B, Collet C. Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis. J Am Heart Assoc. 2022 Apr 5;11(7):e023207. doi: 10.1161/JAHA.121.023207. Epub 2022 Mar 18.
PubMed 35301851Yao GH, Zhang C, Sun FR, Zhang M, Zhao YX, Zhang PF, Zhong L, Ding SF, Chen WQ, Li XN, Zhang Y. Quantification of transmural gradient of blood flow in myocardial ischemia with real-time myocardial contrast echocardiography and dipyridamole stress test. Ultrasound Med Biol. 2008 Jan;34(1):22-30. doi: 10.1016/j.ultrasmedbio.2007.06.019. Epub 2007 Sep 14.
PubMed 17854984Effects of Carvedilol on Coronary Flow Reserve in EH Patients with Left Ventricular Hypertrophy by Transesophageal Echocardiography
Qu Haiyan, Zhang Mei, Yao Guihua, et al. Early diagnosis of myocardial ischemia by strain rate imaging during adenosine stress echocardiography. Chin J Ultrasonogr,2006,15(1):50-53
Prasad M, McBane R, Reriani M, Lerman LO, Lerman A. Coronary endothelial dysfunction is associated with increased risk of venous thromboembolism. Thromb Res. 2016 Mar;139:17-21. doi: 10.1016/j.thromres.2015.12.024. Epub 2015 Dec 29.
PubMed 26916291Michelsen MM, Pena A, Mygind ND, Frestad D, Gustafsson I, Hansen HS, Kastrup J, Bech J, Host N, Prescott E. Coronary Flow Velocity Reserve Assessed by Transthoracic Doppler: The iPOWER Study: Factors Influencing Feasibility and Quality. J Am Soc Echocardiogr. 2016 Jul;29(7):709-16. doi: 10.1016/j.echo.2016.02.011. Epub 2016 Mar 31.
PubMed 27038514Mygind ND, Michelsen MM, Pena A, Frestad D, Dose N, Aziz A, Faber R, Host N, Gustafsson I, Hansen PR, Hansen HS, Bairey Merz CN, Kastrup J, Prescott E. Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study. J Am Heart Assoc. 2016 Mar 15;5(3):e003064. doi: 10.1161/JAHA.115.003064.
PubMed 27068634Porter TR, Abdelmoneim S, Belcik JT, McCulloch ML, Mulvagh SL, Olson JJ, Porcelli C, Tsutsui JM, Wei K. Guidelines for the cardiac sonographer in the performance of contrast echocardiography: a focused update from the American Society of Echocardiography. J Am Soc Echocardiogr. 2014 Aug;27(8):797-810. doi: 10.1016/j.echo.2014.05.011. No abstract available.
PubMed 25085408Mulvagh SL, Rakowski H, Vannan MA, Abdelmoneim SS, Becher H, Bierig SM, Burns PN, Castello R, Coon PD, Hagen ME, Jollis JG, Kimball TR, Kitzman DW, Kronzon I, Labovitz AJ, Lang RM, Mathew J, Moir WS, Nagueh SF, Pearlman AS, Perez JE, Porter TR, Rosenbloom J, Strachan GM, Thanigaraj S, Wei K, Woo A, Yu EH, Zoghbi WA; American Society of Echocardiography. American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography. J Am Soc Echocardiogr. 2008 Nov;21(11):1179-201; quiz 1281. doi: 10.1016/j.echo.2008.09.009.
PubMed 18992671