Persantin Preceding Elective PCI (P3)

Does Pretreatment With Persantin Reduce Periprocedural Troponin-I Release in Patients Undergoing Elective Single Vessel PCI

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.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Coronary Heart Disease; Percutaneous Transluminal Coronary Angioplasty
• Intervention / Treatment: Drug: dipyridamole; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500HB
    • RUNMC
  • Nijmegen, Netherlands, 6532SZ
    • Canisius Wilhelmina Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients accepted for elective single, native vessel (left anterior descending, right coronary artery or ramus circumflexus (LAD, RCA or RCX)) PCI in the RUNMC
• Troponin-I < 0,20 mmol/L at screening
• Signed Informed consent

Exclusion Criteria:

• unstable angina
• recent myocardial infarction (STEMI or non-STEMI), during two weeks prior to inclusion
• 3-Vessel disease as seen on coronary angiogram
• Stenotic lesion in main stem as seen on coronary angiogram
• CABG in medical history
• asthma (recurrent episodes of dyspnoea and wheezing, or usage of prescribed inhalation medication: i.e. corticosteroids or B2-agonists)
• Treatment with insulin
• Use of prescribed oral anticoagulants (coumarin derivates)
• Use of oral corticosteroids
• Use of sulfonylurea derivates (glibenclamide, tolbutamide, gliclazide, glimepiride)
• Use of heparin or low molecular weight heparin
• Use of metformin
• Use of dipyridamole
• Chronic use of Non Steroid Anti-Inflammatory Drugs (NSAID's)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; placebo	Drug: placebo; placebo twice daily, minimal three days pretreatment
Experimental: 1; dipyridamole	Drug: dipyridamole; dipyridamole slow release 200mg twice daily, minimal 3 days pretreatment; Other Names: persantin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cardiac troponin-I	before and 8 hours after PCI

Secondary Outcome Measures

Outcome Measure	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)	before and 8 hours after PCI

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Gerard Rongen, MD PhD, RUNMC

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: Lancet. 2007 Jan 27;369(9558):274.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 6, 2008
• First Posted (Estimate): October 7, 2008

Study Record Updates

• Last Update Posted (Estimate): October 30, 2015
• Last Update Submitted That Met QC Criteria: October 29, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Phosphodiesterase Inhibitors; Dipyridamole
• Other Study ID Numbers: P3