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Completed

NCT Number: NCT01295567

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

RUNMC

Nijmegen, 6500HB, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

dipyridamole

Drug

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

Other names: persantin

Placebo

Drug

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

Primary outcomes

  1. HS-troponin-I

    Time frame: within 72 hours after CABG.

    high sensitivity cardiac troponin-I

Secondary outcomes

  1. duration of inotropic support

    Time frame: within three days after CABG

  2. duration of IC stay

    Time frame: within three days after CABG

  3. drain production

    Time frame: 24 hours after surgery and total drain production within three days after surgery

    thoracic drain production after CABG

  4. post-ischemic recovery of contractile function

    Time frame: until 4 hours after harvesting

    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

  5. Renal damage

    Time frame: Within three days after CABG

    biomarkers for renal failure will be detemined in blood and urine before and after CABG

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Feb 14, 2011
Registry last updated
Jan 10, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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