The primary objective of this study is to assess whether adding modified-release dipyridamole to aspirin (Asasantin Retard) has measurable effects on markers of platelet function (for example, platelet aggregation) in patients with cardiovascular disease who are known to be resistant to aspirin alone

Condition	Intervention	Phase
Coronary Arteriosclerosis	Drug: aspirin  Drug: modified-release dipyridamole/aspirin	Phase IV

Further Study Details: 

Primary Outcomes: The primary endpoint will be the proportion of patients classified as aspirin-resistant at the end of each treatment period (i.e. day 30)
Secondary Outcomes: Serum thromboxane B2, platelet aggregation (after epinephrine, ADP or collagen), plasma CD40L, markers of platelet activation, urine prostaglandins, bleeding time, blood prostaglandins and markers of blood coagulation
Expected Total Enrollment:  22

The primary objective of this study is to determine whether adding modified-release dipyridamole to aspirin (Asasantin Retard) has measurable effects on markers of platelet function (for example platelet aggregation) in patients with cardiovascular disease who are known to be resistant to aspirin alone. Resistance to aspirin is defined as platelet aggregation of at least 20% (of maximum possible aggregation in response to arachidonic acid) after usual therapeutic doses of aspirin (at least 75 mg/day).

This is a randomised double-blind, double-dummy, placebo-controlled, two-period crossover study with no washout between treatment periods. The durations of the treatment periods are 30 days each. At randomisation, all patients will receive one active drug (and placebo matching the comparator drug) for 30 days and will then crossover to the alternative active drug (and placebo matching alternative comparator drug) for 30 days. The treatments being compared are modified-release dipyridamole/aspirin combination (200 mg/25 mg twice daily; Asasantin Retard) and aspirin (75 mg once daily). On each test day, patients will have blood samples taken for assessment of markers of platelet function.

Enough patients will be randomised to ensure that at least twenty (20) evaluable patients complete the study protocol.

Study Hypothesis:

The primary endpoint will be the comparison of the effects of study treatment on platelet aggregation in response to arachidonic acid. It is hypothesised that at least 20% of these aspirin-resistant patients will not be resistant to aspirin during the modified-release dipyridamole/aspirin treatment period whereas all patients are expected to be resistant to aspirin during the aspirin treatment period

Comparison(s):

The primary analysis will compare the proportions of aspirin-resistant patients under the two treatments. The proportions at the end of each treatment period will be compared. The primary endpoint will be the comparison of the effects of either treatment on platelet aggregation in response to arachidonic acid. It is hypothesised that at least 20% of these aspirin-resistant patients will not be resistant to aspirin during the modified-release dipyridamole/aspirin treatment period whereas all patients are expected to be resistant to aspirin during the aspirin treatment period.

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

Cardiovascular disease (including history of stroke or transient ischaemic attack) Documented evidence of resistance to aspirin Capable of comprehending and communicating effectively with the investigator and staff and of providing informed consent.

Willing to give informed consent prior to participation in the trial.

Exclusion criteria:

Any clinically significant condition other than cardiovascular disease. Clinically significant abnormal baseline haematology, blood chemistry or urinalysis findings.

Use of dipyridamole, clopidogrel, ticlopidine or any non-steroidal anti-inflammatory agent (NSAID)(including COX-2 inhibitors) during the two weeks before randomisation and during the trial.

Active peptic ulceration or history of peptic ulcer disease. Known history of or suspected hypersensitivity to dipyridamole, aspirin, any NSAID or any other component of the test drugs.

History of any bleeding disorder. History of cerebral haemorrhage. Resting seated blood pressure less than 90/60mmHg. Participation in any drug clinical trial within sixteen weeks prior to the start of the trial.

Any indication of current or previous abuse of alcohol, solvents or drugs. Asthma. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (e.g. oral contraceptives, intrauterine devices or surgically sterile).

Previous participation in the randomisation phase of this clinical trial.

Please refer to this study by ClinicalTrials.gov identifier  NCT00129038

Colin Edwards, Dr      +353 (1) 295-9620  Ext. 2959620    Colin.Edwards@dbl.Boehringer-Ingelheim.com

Ireland
      PO Box 1297, Dublin,  9,  Ireland; Recruiting
      St. James'''' Hospital, Dublin,  8,  Ireland; Recruiting

Study chairs or principal investigators

Colin Edwards, Dr,  Study Chair,  BIL UK / Ireland   

Study ID Numbers:  9.169
Last Updated:  August 10, 2005
Record first received:  August 10, 2005
ClinicalTrials.gov Identifier:  NCT00129038
Health Authority: Ireland: Irish Medicines Board
ClinicalTrials.gov processed this record on 2005-08-23