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

NCT ID: NCT01295567

Last Updated: 2013-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-09-30

Brief 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.

Conditions

Cardiovascular Disease; Ischemic Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

prior to CABG surgery 3 day treatment with placebo capsules twice daily

dipyridamole

Group Type: EXPERIMENTAL

Dipyridamole

Intervention Type: DRUG

prior to CABG surgery 3 day treatment with dipyridamole 200mg SR twice daily

Interventions

Dipyridamole

prior to CABG surgery 3 day treatment with dipyridamole 200mg SR twice daily

Intervention Type: DRUG

placebo

prior to CABG surgery 3 day treatment with placebo capsules twice daily

Intervention Type: DRUG

Other Intervention Names

persantin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

G. Rongen

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

RUNMC

Nijmegen, , Netherlands

Countries

Netherlands

References

El Messaoudi S, Wouters CW, van Swieten HA, Pickkers P, Noyez L, Kievit PC, Abbink EJ, Rasing-Hoogveld A, Bouw TP, Peters JG, Coenen MJ, Donders AR, Riksen NP, Rongen GA. Effect of dipyridamole on myocardial reperfusion injury: A double-blind randomized controlled trial in patients undergoing elective coronary artery bypass surgery. Clin Pharmacol Ther. 2016 Apr;99(4):381-9. doi: 10.1002/cpt.106. Epub 2015 Oct 22.

Reference Type: DERIVED

PMID: 25773594 (View on PubMed)

Other Identifiers

2009-014299-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

dipy-cabg

Identifier Type: -

Identifier Source: org_study_id