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In this study the investigators will investigate whether a short pretreatment (3-7 days) with dipyridamole 200mg twice daily will protect patients against myocardial injury sustained during an elective dotter operation of the coronary arteries (PCI).
The investigators hypothesize that dipyridamole can reduce myocardial injury sustained during elective PCI.
Rationale:
In elective PCI (percutaneous coronary intervention) up to 40% of the patients show an asymptomatic rise in myonecrosis marker troponin-I. This release of troponin-I has been found to represent irreversible myocardial injury and has been related to an increased risk of restenosis and even long-term mortality. Dipyridamole has been proven to induce protection against ischemia reperfusion injury and to reduce risk of cardiovascular death or event in secondary prevention after TIA or CVA.
Objective:
To test the hypothesis that dipyridamole improves tolerance to ischemia reperfusion injury in patients undergoing elective PCI.
Study design:
Double-blind placebo controlled intervention study
Study population:
Patients undergoing elective PCI
Intervention:
pretreatment with dipyridamole (Persantin Retard) 2dd 200mg or placebo.
Main study parameters:
Periprocedural troponin-I release measured 8 hours after PCI.
Bioequivalence study:
before the start of th clinical trial we will perform a bioequivalent study to test whether our study medication (blinded by recapsuling) equals original dipyridamole capsules. 6 Healthy volunteers in a cross-over randomised design will take original dipyridamole 200 mg SR and recapsuled dipyridamole 200mg SR (prepared by the department of pharmacy of the RUNMC). Plasma dipyridamole concentration will be measured frequently and at baseline and 1 and 3 hours after administration of dipyridamole nucleoside transport inhibitions of erythrocytes will be measured, to assess drug activity.
The clinical trial will only be initialized after conformation of bioequivalence of the study medication to the original dipyridamole.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | dipyridamole |
|
| 2 | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dipyridamole | Drug | dipyridamole slow release 200mg twice daily, minimal 3 days pretreatment |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac troponin-I | before and 8 hours after PCI |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of pretreatment with dipyridamole 2x200mg on biomarkers reflecting vascular inflammation (hs-CRP, PLA2, PTX3, IL-6, adiponectin, MCP-1, MMP-9) | 3 days treatment minimal | |
| Effect of PCI on biomarkers reflecting vascular inflammation (hs-CRP, PLA2, PTX3, IL-6, adiponectin, MCP-1, MMP-9) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerard Rongen, MD PhD | RUNMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| RUNMC | Nijmegen | 6500HB | Netherlands | |||
| Canisius Wilhelmina Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17084248 | Background | Kleiman NS. Measuring troponin elevation after percutaneous coronary intervention: ready for prime time? J Am Coll Cardiol. 2006 Nov 7;48(9):1771-3. doi: 10.1016/j.jacc.2006.08.008. Epub 2006 Oct 17. No abstract available. | |
| 16714187 | Background | ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73. doi: 10.1016/S0140-6736(06)68734-5. |
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| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D004176 | Dipyridamole |
| ID | Term |
|---|---|
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| placebo | Drug | placebo twice daily, minimal three days pretreatment |
|
| before and 8 hours after PCI |
| Nijmegen |
| 6532SZ |
| Netherlands |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |