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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
G. Rongen, Radboud University
ClinicalTrials.gov Identifier:
NCT01295567
First received: February 1, 2011
Last updated: January 8, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Cardiovascular Disease
Ischemic Heart Disease
 Drug: Dipyridamole
Drug: placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Can Dipyridamole Induce Protection Against Ischemia and Reperfusion Injury in Patients Undergoing Elective CABG?

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • HS-troponin-I [ Time Frame: within 72 hours after CABG. ] [ Designated as safety issue: No ]
    high sensitivity cardiac troponin-I


Secondary Outcome Measures:
  • duration of inotropic support [ Time Frame: within three days after CABG ] [ Designated as safety issue: No ]
  • duration of IC stay [ Time Frame: within three days after CABG ] [ Designated as safety issue: No ]
  • drain production [ Time Frame: 24 hours after surgery and total drain production within three days after surgery ] [ Designated as safety issue: Yes ]
    thoracic drain production after CABG

  • post-ischemic recovery of contractile function [ Time Frame: until 4 hours after harvesting ] [ Designated as safety issue: No ]
    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

  • Renal damage [ Time Frame: Within three days after CABG ] [ Designated as safety issue: No ]
    biomarkers for renal failure will be detemined in blood and urine before and after CABG


Enrollment: 95
Study Start Date: December 2009
Study Completion Date: September 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo Drug: placebo
prior to CABG surgery 3 day treatment with placebo capsules twice daily
Experimental: dipyridamole Drug: Dipyridamole
prior to CABG surgery 3 day treatment with dipyridamole 200mg SR twice daily
Other Name: persantin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01295567

Locations
Netherlands
RUNMC
Nijmegen, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
  More Information

No publications provided

Responsible Party: G. Rongen, professor, Radboud University
ClinicalTrials.gov Identifier: NCT01295567     History of Changes
Other Study ID Numbers: dipy-cabg, 2009-014299-22
Study First Received: February 1, 2011
Last Updated: January 8, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
ischemia reperfusion injury
CABG
dipyridamole
HS-troponin-I

Additional relevant MeSH terms:
Cardiovascular Diseases
Coronary Artery Disease
Myocardial Ischemia
Heart Diseases
Ischemia
Reperfusion Injury
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
 Postoperative Complications
Dipyridamole
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 16, 2013