The Effect of Dan-shen Extract On Lipoprotein Associated PHospholipase A2 Levels IN Patients With Stable Angina Pectoris (DOLPHIN)

A Randomized, Double-blind, Placebo-controlled Trial of Dan-shen Extract in Patients With Stable Angina Pectoris

This is a randomized, double-blind, placebo-controlled, adaptive clinical trial, which will assess the effect of DanshenDuofensuanyan[Danshen (a kind of Chinese herbal drug) extract] treatment on Lipoprotein associated phospholipase A2 level in patients with stable angina pectoris.

Study Overview

• Status: Unknown
• Conditions: Inflammation; Angina, Stable
• Intervention / Treatment: Other: Standard medical care; Drug: Dan-shen extract; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Taizhou, Jiangsu, China, 225300
      • Recruiting
      • Taizhou Fourth People's Hospital
      • Contact: Bailing Su, MD; Phone Number: 0086052380185012; Email: tzsybgs055@sina.com
      • Contact: Haoshen Wang, MD; Phone Number: 008613952613616; Email: billet1116@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age:18 years-75 years;
2. Written informed consent;

3. Patients with a clinical diagnosis of chronic stable angina, which fulfil one of the following conditions:

   1. Symptoms that support the diagnosis of chronic angina and/or a history of an abnormal exercise response limited by angina and/or electrocardiograph (ECG) changes
   2. a history of myocardial infarction and ST-T changes,
   3. stenosis of more than 50 % in at least one major epicardial coronary artery, as shown by coronary angiography or computed tomography angiography,
   4. Coronary heart disease confirmed by radionuclide angiocardiography;
4. Patients with moderate angina pectoris, which is defined as Grade II or III on the Canadian Cardiovascular Society Angina Grading Scale.

Exclusion Criteria:

1. Patients with severe complications that would complicate the condition, as assessed by the investigator, including liver or renal dysfunction, severe cardiopulmonary dysfunction, pulmonary hypertension, chronic obstructive pulmonary disease, a history of epilepsy or cerebral haemorrhage.
2. Patients who were angina-free during the run-in period without taking any drug.
3. Patients who experienced myocardial infarction or who were classified as Grade IV on the Canadian Cardiovascular Society Angina Grading Scale within the preceding 3 months.
4. Patients with chest pain that is caused by any other disease (e.g., acute myocardial infarction, severe neurosis, menopausal syndrome or hyperthyroidism).
5. Patients with a history of drug-induced bleeding or a history of bleeding caused by warfarin.
6. Patients with a history of haematopoietic disorder.
7. Patients who have had surgery within the previous 4 weeks or who have a haemorrhagic tendency.
8. Women who are pregnant or lactating or who have a positive pregnancy test, or women who have a menstrual period at baseline.
9. Patients who are participating in other trials or who have participated in other trials within the past 3 months.
10. Patients with a history of allergy or with a known or suspected allergy to the study drug.
11. Patients with a known or suspected history of alcohol or drug abuse within the past 2 years.
12. Patients with a mental disorder.
13. Family members or relatives of the study centre staff.
14. Inability to adhere to study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Dan-shen extract; Based on the standard medical care, 200mg of Danshenduofensuanyan, added into 250ml of 0.9% saline injection, given by continuous IV infusion at 2.5ml/min within 2 hours, once a day during the patients' hospitalization. Danshen drop spill (30 pill/day) taken orally for 60 days after discharge.	Other: Standard medical care; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of Chronic Stable Angina (2007).; Drug: Dan-shen extract; A kind of injection made from a kind of Chinese herb: salvia miltiorrhiza; Other Names: salvianolic acid; Depside salt from Salvia Miltiorrhiza; Danshen Dropping Pill; dropping salvia pill
PLACEBO_COMPARATOR: Placebo; Based on the standard medical care, placebo was 200mg of glucose, added into 250ml of 0.9% saline injection, given by continuous IV infusion at 2.5ml/min within 2 hours.	Other: Standard medical care; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of Chronic Stable Angina (2007).; Drug: Placebo; 200mg glugose added into 250ml 0.9% saline injection by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, using brown infusion tube for infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum level of Lp-PLA2	up to Day 60 after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients in each treatment group who had clinically significant change as defined by the angina-frequency score on the Seattle Angina Questionnaire		Day 0 and Day 60 after discharge
carotid arterial intima-media wall thickness		Day0 and Day 60 after discharge
Canadian Cardiovascular Society (CCS) grading of angina pectoris		Day 0 and Day 60 after discharge
Change in the electrocardiogram (EKG)		Day 0 and Day 60 after discharge
Changes in the Serum Lipid, the high-sensitivity C-Reactive Protein(hs-CRP) and the Platelet Aggregation Rate		Day 0 and Day 60 after discharge
Incidence of new-onset major vascular events	Major adverse vascular events include ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction and vascular-related death.	up to 60 days after discharge
Incidence of severe hemorrhages	The definition of "Severe hemorrhages" is in accordance with the GUSTO bleeding criteria, including fatal intracranial hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) or which could result in substantial hemodynamic compromise requiring treatment.	up to 60 days after discharge
Incidence of moderate hemorrhages	The definition of "moderate hemorrhages" is in accordance with the GUSTO bleeding criteria, which requires blood transfusion but not results in hemodynamic compromise.	up to 60 days after discharge

Collaborators and Investigators

• Sponsor: Taizhou Fourth People's Hospital
• Collaborators: Shanghai 10th People's Hospital
• Investigators: Study Chair: A'Di Chen, Master, Taizhou Fourth People's Hospital

Publications and helpful links

General Publications

• Li B, Wang Y, Lu J, Liu J, Yuan Y, Yu Y, Wang P, Zhao X, Wang Z. Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial. Trials. 2015 Dec 9;16:561. doi: 10.1186/s13063-015-1076-4.
• Wang PQ, Li DD, Dong W, Liu J, Yu YN, Shen CT, Chen QG, Chen BW, Chen YD, Wang Z. Danhong injection in the treatment of chronic stable angina: study protocol for a randomized controlled trial. Trials. 2015 Oct 21;16:474. doi: 10.1186/s13063-015-0998-1.
• Yao Y, Feng Y, Lin W. Systematic review and meta-analysis of randomized controlled trials comparing compound danshen dripping pills and isosorbide dinitrate in treating angina pectoris. Int J Cardiol. 2015 Mar 1;182:46-7. doi: 10.1016/j.ijcard.2014.12.112. Epub 2014 Dec 29. No abstract available.
• Cheng TO. Cardiovascular effects of Danshen. Int J Cardiol. 2007 Sep 14;121(1):9-22. doi: 10.1016/j.ijcard.2007.01.004. Epub 2007 Mar 23.
• Cai A, Li G, Chen J, Li X, Li L, Zhou Y. Increased serum level of Lp-PLA2 is independently associated with the severity of coronary artery diseases: a cross-sectional study of Chinese population. BMC Cardiovasc Disord. 2015 Feb 26;15:14. doi: 10.1186/s12872-015-0001-9.
• White HD, Simes J, Stewart RA, Blankenberg S, Barnes EH, Marschner IC, Thompson P, West M, Zeller T, Colquhoun DM, Nestel P, Keech AC, Sullivan DR, Hunt D, Tonkin A; LIPID Study Investigators. Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. J Am Heart Assoc. 2013 Oct 23;2(5):e000360. doi: 10.1161/JAHA.113.000360.
• Chen AD, Wang CL, Qin Y, Tian L, Chen LB, Yuan XM, Ma LX, Wang YF, Sun JR, Wang HS, Dai N; DOLPHIN investigator group. The effect of Danshen extract on lipoprotein-associated phospholipase A2 levels in patients with stable angina pectoris: study protocol for a randomized controlled trial - the DOLPHIN study. Trials. 2017 Dec 20;18(1):606. doi: 10.1186/s13063-017-2336-2.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ANTICIPATED): May 1, 2017
• Study Completion (ANTICIPATED): August 1, 2017

Study Registration Dates

• First Submitted: August 13, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (ESTIMATE): August 17, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): September 13, 2016
• Last Update Submitted That Met QC Criteria: September 11, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: coronary artery disease; Lp-PLA2; Salvia miltiorrhiza; Danshenduofensuanyan
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Inflammation; Angina Pectoris; Angina, Stable
• Other Study ID Numbers: TaizhouFPH-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We could provide individual participant data without leaking the patients' personal information if needed.