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

NCT01295567 | Completed Phase 4 DMC

• 2 other identifiers: dipy-cabg2009-014299-22
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

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

Keywords

ischemia reperfusion injury; CABG; dipyridamole; HS-troponin-I

Outcome Measures

Primary Outcomes (1)

• HS-troponin-I

  high sensitivity cardiac troponin-I

  within 72 hours after CABG.

Secondary Outcomes (5)

• duration of inotropic support

  within three days after CABG

• duration of IC stay

  within three days after CABG

• drain production

  24 hours after surgery and total drain production within three days after surgery

• post-ischemic recovery of contractile function

  until 4 hours after harvesting

• Renal damage

  Within three days after CABG

Study Arms (2)

placebo

PLACEBO COMPARATOR

Drug: placebo

dipyridamole

EXPERIMENTAL

Drug: Dipyridamole

Interventions

Dipyridamole DRUG

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

Also known as: persantin

dipyridamole

placebo DRUG

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

placebo

Eligibility Criteria

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

You may qualify if:

• Acceptation for CABG in RUNMC
• Informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

RUNMC

Nijmegen, 6500HB, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 25773594 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Myocardial Ischemia; Reperfusion Injury

Interventions

Dipyridamole

Condition Hierarchy (Ancestors)

Heart Diseases; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: February 1, 2011
• First Posted: February 14, 2011
• Study Start: December 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: September 1, 2012
• Last Updated: January 10, 2013

Record last verified: 2013-01

Locations

NL (1)