Can Dipyridamole Induce Protection Against Ischemia and Reperfusion Injury in Patients Undergoing Elective Coronary Artery Bypass Grafting (CABG)?

Cardiovascular Disease Clinical Trial

Official title:

Can Dipyridamole Induce Protection Against Ischemia and Reperfusion Injury in Patients Undergoing Elective CABG?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01295567
• Other study ID #: dipy-cabg
• Secondary ID: 2009-014299-22
• Status: Completed
• Phase: Phase 4
• First received: February 1, 2011
• Last updated: January 8, 2013
• Start date: December 2009
• Est. completion date: September 2012

Study information

• Verified date: January 2013
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Rationale:

Due to western lifestyle human coronary arteries are prone to develop atherosclerotic plaques. Hence the heart is an important target organ for atherothrombotic complications: myocardial ischemia, arrhythmias, myocardial infarction and heart failure. To alleviate symptoms and decrease mortality in these patients, myocardial revascularisation is recommended. Coronary artery bypass grafting (CABG) is indicated in patients with severe atherosclerotic disease of all three coronary arteries or the left main stem coronary artery. Cardiac ischemia and reperfusion injury during CABG is inevitable and jointly accountable for complications that occur after CABG (e.g. death, myocardial infarction, arrhythmias, stroke, or renal complications). Dipyridamole has been shown to reduce ischemia reperfusion injury in healthy volunteers using an intermediate endpoint and may prevent cardiovascular death or event in secondary prevention after cerebrovascular disease. The investigators hypothesise that oral pre-treatment with dipyridamole can increase cardiac tissue tolerance against ischemia and reperfusion injury due to CABG. The investigators expect lower troponin-I release in patients who were pretreated with dipyridamole.

Objective: To study the effect of oral pretreatment with dipyridamole on high sensitivity (HS)-troponin-I release after CABG. Secondary objectives are whether oral pretreatment with dipyridamole reduces postoperative CABG arrhythmias, prolonged inotropic support, and duration of Intensive Care-stay. Further secondary endpoints are the effects of dipyridamole pretreatment on renal injury and post-ischemic recovery of contractile function (measured ex-vivo).

Hypothesis:

The investigators hypothesize that oral pre-treatment with dipyridamole can increase cardiac tissue tolerance against ischemia and reperfusion injury. The investigators expect lower HS-troponin-I release in patients who were pretreated with dipyridamole. Additionally the investigators expect the incidence of arrhythmias, need for prolonged inotropic support (longer than 24 hours postoperative) to be decreased in pretreated patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: September 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Acceptation for CABG in RUNMC

• Informed consent

Exclusion Criteria:

• Recent myocardial infarction (STEMI or non-STEMI), during two weeks prior to inclusion

• Asthma

• Use of insulin

• Use of sulfonylurea derivates (e.g. glibenclamide, tolbutamide, gliclazide, glimepiride)

• Use of metformin

• Use of oral corticosteroids

• Use of dipyridamole

• Use of clopidogrel within 8 days prior to scheduled CABG surgery

• Chronic use of Non Steroid Anti-Inflammatory Drugs (NSAIDs)

• Off-pump surgery

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Coronary Artery Disease
• Ischemic Heart Disease
• Myocardial Ischemia
• Reperfusion Injury

Intervention

Drug:
• Dipyridamole
prior to CABG surgery 3 day treatment with dipyridamole 200mg SR twice daily
• placebo
prior to CABG surgery 3 day treatment with placebo capsules twice daily

Locations

Country	Name	City	State
Netherlands	RUNMC	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HS-troponin-I	high sensitivity cardiac troponin-I	within 72 hours after CABG.	No
Secondary	duration of inotropic support		within three days after CABG	No
Secondary	duration of IC stay		within three days after CABG	No
Secondary	drain production	thoracic drain production after CABG	24 hours after surgery and total drain production within three days after surgery	Yes
Secondary	post-ischemic recovery of contractile function	The right atrial appendage is harvested during cardiac surgery before the introduction of the extracorporal circulation. Two atrial trabeculae are dissected, suspended in an organ bath, and linked to a force transducer. after equilibration and baseline measurement, simulated ischemia and reperfusion influences contractile force recovery	until 4 hours after harvesting	No
Secondary	Renal damage	biomarkers for renal failure will be detemined in blood and urine before and after CABG	Within three days after CABG	No