Coronary MicrovAscular Diseases Intervention With Compound Danshen Dropping Pills

NCT07885462 | Not Yet Recruiting Phase 4

• 1 other identifier: KYLL-2026-04(XZ)-004-2
• Study Type: interventional
• Target: 496
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Coronary Microvascular Disease

Keywords

Coronary Flow Reserve; Major adverse cardiovascular events; Seattle Angina Questionnaire; Canadian Cardiovascular Society Angina Class

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 6 months, and 12 months

Secondary Outcomes (4)

• Change from baseline in mean coronary flow reserve (CFRmean) of the left anterior descending artery

  Baseline, 6 months, and 12 months

• Change from baseline in Seattle Angina Questionnaire (SAQ) score

  Baseline, 3, 6, 9, and 12 months

• Change from baseline in CCS angina class

  Baseline, 3, 6, 9, and 12 months

• Incidence of major adverse cardiovascular events (MACE) within 12 months

  From randomization/enrollment through 12 months

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Compound Danshen Dripping Pills DRUG

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.

Also known as: CDDP, Fufang Danshen Diwan, Cardiotonic Pill, Dantonic Pill, T89

Conventional treatment + Compound Danshen Dripping Pills 540 mg

Placebo DRUG

Placebo pills identical to Compound Danshen Dripping Pills in appearance, taste, and packaging, 20 pills orally three times daily for 12 months.

Also known as: Matching placebo

Conventional treatment + matching placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Voluntary provision of written informed consent by the subject or legal representative.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu Hospital of Shandong University

Jinan, Shandong, 250000, China

Location

Related Publications (13)

• 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.

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• Zhang 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.

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 20579539 BACKGROUND

• Mileva 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.

  PMID: 35301851 BACKGROUND

• Yao 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.

  PMID: 17854984 BACKGROUND

• Effects of Carvedilol on Coronary Flow Reserve in EH Patients with Left Ventricular Hypertrophy by Transesophageal Echocardiography

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 26916291 BACKGROUND

• Michelsen 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.

  PMID: 27038514 BACKGROUND

• Mygind 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.

  PMID: 27068634 BACKGROUND

• Porter 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.

  PMID: 25085408 BACKGROUND

• Mulvagh 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.

  PMID: 18992671 BACKGROUND

MeSH Terms

Conditions

Microvascular Angina

Interventions

Cardiotonic Agents; T89 herbal drug

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Protective Agents; Specialty Uses of Chemicals

Study Officials

• Yun Zhang, MD,PhD

  Department of Cardiology,Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

XiaoLing Zhang, MD

CONTACT

+86-18560086718; xiaolingliusdu@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tenured Professor of Shandong University, Academician of the Chinese Academy of Engineering, Fellow of the American College of Cardiology (FACC), Chief of the Department of Cardiology

Model Details: Randomized, double-blind, placebo-controlled, multicenter clinical trial.

Study Record Dates

• First Submitted: October 12, 2026
• First Posted: October 21, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)