The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD) - Full Text View

Purpose

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.

Condition	Intervention
Peripheral Arterial Disease	Drug: Dipyridamole 200mg and Aspirin 25mg bid: Drug: Dipyridamole 200 mg bid Drug: Aspirin 25 mg bid

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)

Resource links provided by NLM:

MedlinePlus related topics: Peripheral Arterial Disease Vascular Diseases

Drug Information available for: Aspirin Dipyridamole

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

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. [ Time Frame: Predose and dosing days 30, 90 and 180 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assess the functional consequences of dipyridamole action, alone and in combination with aspirin compared with aspirin alone on local measurements of flow and oxygenation. [ Time Frame: Predose and dosing days 30, 90 and 180. ] [ Designated as safety issue: No ]

Enrollment:	51
Study Start Date:	September 2002
Study Completion Date:	April 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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.	Drug: 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. Other Name: Persantine
Active Comparator: 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.	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. Other Name: Persantine
Active Comparator: 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.	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.

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).

Eligibility

Ages Eligible for Study:	18 Years to 79 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00906035

Locations

United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

Boehringer Ingelheim Pharmaceuticals

Investigators

Principal Investigator:	Garret A FitzGerald, MD	University of Pennsylvania
Principal Investigator:	Emile R Mohler, MD	University of Pennsylvania

More Information

No publications provided

Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00906035 History of Changes
Other Study ID Numbers:	706469, 0821
Study First Received:	May 20, 2009
Last Updated:	January 31, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pennsylvania:

Peripheral Arterial Disease
PAD
Claudication
Peripheral Vascular Disease

Additional relevant MeSH terms:

Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Aspirin
Dipyridamole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Phosphodiesterase Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013