The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)

NCT ID: NCT00906035

Last Updated: 2017-09-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2010-04-30

Brief Summary

This research study will evaluate the effects of aspirin and dipyridamole alone and in combination on the blood flow in the vessels of the legs. We will examine how these medications are able to inhibit the clotting of platelets in the vessels of patients with PAD, and thereby affect the blood flow in the legs. Platelets are cells in the blood that have the ability to adhere to each other to form clots.

Detailed Description

Dipyridamole has been reformulated to guarantee systemic bioavailability and steady state levels compatible with inhibition of platelet aggregation ex vivo (1). This newly formulated dipyridamole has been shown to roughly equal in efficacy to low dose aspirin in the secondary prevention of stroke and the drug combination seems roughly additive (2). The present study is designed to explore two potential mechanisms which have been linked to dipyridamole action on the vessel wall; modulation of vascular eicosanoid generation and prevention of oxidant stress (3). We shall address the hypothesis that dipyridamole affects these systems in patients with PAD. These individuals have disordered platelet-vascular interactions, as reflected by increased generation of thromboxane, an index of platelet activation and of prostacyclin, probably a homeostatic response to traumatic and chemical stimulation of the endothelium (4,5). Furthermore, we shall assess the functional consequences of dipyridamole action, alone and in combination with aspirin compared with aspirin alone on local measurements of flow and oxygenation, including exercise tolerance, Doppler Ultrasound and Near Infrared Spectroscopy (NIRS). Lipid peroxidation will be quantified based on mass spectrometric analysis of the major urinary isoprostane, 8,12-iso-iPF2a-VI (6,7).

Conditions

Peripheral Arterial Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dipyridamole 200mg and Aspirin 25mg bid

All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy. (NIRS) of the legs.

Group Type: ACTIVE_COMPARATOR

Dipyridamole 200mg and Aspirin 25mg bid:

Intervention Type: DRUG

All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Dipyridamole 200 mg bid

All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy. (NIRS) of the legs.

Group Type: ACTIVE_COMPARATOR

Dipyridamole 200 mg bid

Intervention Type: DRUG

All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Aspirin 25 mg bid

All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy (NIRS) of the legs.

Group Type: ACTIVE_COMPARATOR

Aspirin 25 mg bid

Intervention Type: DRUG

All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Interventions

Dipyridamole 200mg and Aspirin 25mg bid:

All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Intervention Type: DRUG

Dipyridamole 200 mg bid

All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Intervention Type: DRUG

Aspirin 25 mg bid

All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Intervention Type: DRUG

Other Intervention Names

Persantine; Persantine

Eligibility Criteria

Inclusion Criteria

• Age between 18 - 79
• Women of child bearing potential using a medically acceptable method of birth control (oral/transdermal/vaginal hormonal contraception, depo-provera injection, IUD, condom with spermicide, progestin implant, tubal ligation, oophorectomy, TAH) or abstinence.
• Capacity for giving written consent
• Diagnosis of PAD by:

• previous angiogram (>0.5 stenosis of a peripheral artery)
• ankle-brachial index (ABI) of systolic pressure <0.80
• previous peripheral revascularization
• Smokers who smoke < 10 cigarettes / day

Exclusion Criteria

• Female subjects who are pregnant or nursing a child.
• Prior bleeding event related to drug therapy
• History of gastrointestinal ulceration
• History of known dipyridamole and/or aspirin allergy or intolerance
• History of coagulation, bleeding or blood disorders.
• Recent history of myocardial infarction or stroke in the previous 6 months
• Resting blood pressure of <110mmHg systolic or <60mmHg diastolic or of >165mmHg systolic or >95mmHg diastolic
• Patients with active infection as documented by abnormal laboratory tests at screen
• Concomitant serious illness, such as cancer, as per the principal investigator's discretion
• Current use of steroids for a chronic disease process
• Presence of ischemic leg ulcers
• History of contact allergies to the metal leads of the NIRS
• History of drug or alcohol abuse within the last 6 months.
• Subject who has received an experimental drug and/or used an experimental device within 30 days of screening.
• Subject who has donated ≥ one pint of blood within 8 weeks prior to screen.
• Use of aspirin for 2 weeks prior to the study
• Use of any other NSAID or COX-inhibitor for one week prior to the start of the study
• Use of any antioxidant vitamin for 2 weeks prior to the start of the study
• Use of plavix, pletal or trental for one week prior to the start of the study
• Use of acetaminophen for one week prior to each study visit
• Use of alcohol, caffeine or high fat foods for 24 hours prior to each study visit
• Has smoked any cigarettes for 24 hours prior to each study visit
• Platelet aggregation blood test less than 60 percent at Visit 1

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Garret A FitzGerald, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Emile R Mohler, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Tilo Grosser, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Presbyterian Hospital, 51 N. 39th St.

Philadelphia, Pennsylvania, United States

Translational Research Ctr.,3400 Civic Center Blvd, Building 421, 10th floor, Room 421

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

0821

Identifier Type: -

Identifier Source: secondary_id

706469

Identifier Type: -

Identifier Source: org_study_id