Clinical trial NCT02870764: The Effect of Dan-shen Extract On Lipoprotein Associated PHospholipase A2 Levels IN Patients With Stable Angina Pectoris
Official title: A Randomized, Double-blind, Placebo-controlled Trial of Dan-shen Extract in Patients With Stable Angina Pectoris
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Angina, Stable
Inflammation
Keywords: Danshenduofensuanyan
Lp-PLA2
coronary artery disease
Salvia miltiorrhiza
Lead sponsor: Taizhou Fourth People's Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai 10th People's Hospital
First posted: 2016-08-17
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Serum level of Lp-PLA2
timeFrame: up to Day 60 after discharge
Secondary outcomes:
measure: 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
timeFrame: Day 0 and Day 60 after discharge
measure: carotid arterial intima-media wall thickness
timeFrame: Day0 and Day 60 after discharge
measure: Canadian Cardiovascular Society (CCS) grading of angina pectoris
timeFrame: Day 0 and Day 60 after discharge
measure: Change in the electrocardiogram (EKG)
timeFrame: Day 0 and Day 60 after discharge
measure: Changes in the Serum Lipid, the high-sensitivity C-Reactive Protein(hs-CRP) and the Platelet Aggregation Rate
timeFrame: Day 0 and Day 60 after discharge
measure: Incidence of new-onset major vascular events
timeFrame: up to 60 days after discharge
measure: Incidence of severe hemorrhages
timeFrame: up to 60 days after discharge
measure: Incidence of moderate hemorrhages
timeFrame: up to 60 days after discharge
Other outcomes:
Locations:
city: Taizhou
country: China
facility: Taizhou Fourth People's Hospital
state: Jiangsu
Study officials:
affiliation: Taizhou Fourth People's Hospital
name: A'Di Chen, Master
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.