Clopidogrel and Aspirin for the Treatment of Polycythemia Vera (ISCLAP)

This study has been terminated.
(Could not get drug)
Sponsor:
Information provided by:
Myeloproliferative Disorders-Research Consortium
ClinicalTrials.gov Identifier:
NCT00940784
First received: July 14, 2009
Last updated: June 24, 2011
Last verified: June 2011
  Purpose

Clopidogrel (Plavix) and aspirin are two antithrombotic agents (blood thinners) commonly used in patients with previous thrombotic events (stroke or heart attack). Thrombosis is the formation of a blood clot in a blood vessel. Patients with polycythemia vera are routinely treated with aspirin which has been shown to be effective in reducing their thrombotic risk. However, in polycythemia vera patients with previous thrombosis, a further benefit might be obtained by using the combination of aspirin and clopidogrel which is routinely used in patients with recent acute myocardial ischemia (reduced blood supply to the heart muscle). The study will assess whether this combination therapy greatly increases the risk of bleeding versus aspirin alone, if clopidogrel reduces biological factors that might lead to a stroke or heart attack, and whether a high number of patients with polycythemia vera are resistant to clopidogrel.

Approximately 200 subjects will be enrolled to the Myeloproliferative Disorders-Research Consortium (MPD-RC) study in Europe and the United States with participation expected to last for 7 months (6 months of receiving study medication plus a 30 day follow-up visit).


Condition Intervention Phase
Polycythemia Vera
Drug: Clopidogrel (Plavix)
Drug: Placebo
Drug: Aspirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: MPD-RC 108: Phase II, Randomized, Double-Blind, Placebo Controlled International Study of Clopidogrel and Aspirin for the Treatment of Polycythemia Vera

Resource links provided by NLM:


Further study details as provided by Myeloproliferative Disorders-Research Consortium:

Primary Outcome Measures:
  • To determine the safety and efficacy of using Clopidogrel plus aspirin on Polycythemia Vera patients [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: June 2009
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clopidogrel
Subjects will be randomized to clopidogrel (oral-75 mg per day) in addition to low dose aspirin and hydroxyurea
Drug: Clopidogrel (Plavix)
Clopidogrel, aspirin plus hydroxyurea 75mg qd (Plavix) + 81 - 100 mg qd (aspirin) + hydroxyurea
Other Name: Plavix
Drug: Aspirin
81-100 mg qd
Placebo Comparator: Placebo
Subjects will be randomized placebo in addition to low dose aspirin and hydroxyurea
Drug: Placebo
Placebo, aspirin (81-100 mg qd) plus hydroxyurea
Drug: Aspirin
81-100 mg qd

  Eligibility

Ages Eligible for Study:   18 Years to 81 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients are included in the study if all of the following criteria are met:

  1. A documented diagnosis of polycythemia vera established within 5 years of registration. There must be documentation that the patient has met the revised WHO criteria for the diagnosis of polycythemia vera. Patients must meet the 2 major criteria and 1 of the minor criteria. To verify that the criteria have been met, the appropriate laboratory or pathology reports must be submitted demonstrating that the patient has documentation of these diagnostic criteria.

    Major Criteria:

    • Hemoglobin >18.5 g/dl in men, >16.5 g/dl in women or other evidence of increased red cell volume.
    • Presence of JAK2V617F or other functionally similar mutation such as JAK2 exon 12 mutation

    Minor Criteria:

    • Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocyte, and megakaryocytic proliferation.
    • Serum erythropoietin level below the reference range for normal.
    • Endogenous erythroid colony formation in vitro.
  2. High cardiovascular risk due to having experienced a prior vascular event such as an ischemic stroke, myocardial infarction or venous thromboembolism. Objective documentation of these events must be accurately reviewed and registered. Stroke and pulmonary embolism must be documented by an imaging study, deep vein thrombosis by ultrasound or other objective methods, myocardial infarction by typical ECG changes and/or an increase in serum troponin. Minor thrombotic events such as transient ischemic attacks, superficial thrombophlepitis or atypical microcirculatory disturbances alone or in combination are considered to qualifying events.
  3. No contraindication to aspirin use such as allergy, a history of a previous hemorrhagic stroke or a major gastrointestinal bleed in the previous three months.
  4. Use of hydroxyurea as a cytoreductive agent.
  5. Signed informed consent: Patients must have signed consents for both the ISCLAP protocol and for the mandatory correlative biomarker MPD-RC 107 protocol in order to be eligible.
  6. Serum bilirubin levels less and or equal to 2 times the upper limit of the normal range for the laboratory (ULN).
  7. Serum glutamic-pyruvic transaminase (SGPT) alanine aminotransferase [ALT]) levels and serum aspartate aminotransferase (AST) less and or equal 2 x ULN.
  8. Serum creatinine levels less and or equal 1.5 x ULN.
  9. Women of childbearing potential must have a negative serum or urine pregnancy test prior to clopidogrel treatment and should be advised to avoid becoming pregnant. Women of childbearing potential must practice effective methods of contraception (those generally accepted as standard of care measures). Women of child bearing potential are women who have not been menopausal for 12 months or who have not undergone previous surgical sterilization. If the subject is a woman of childbearing potential, she must use a medically acceptable form of contraception during the study period and for 30 days thereafter.
  10. Age greater than or euql to 18 years to 81 years of age. Exclusion Criteria

Subjects are excluded from participating in this study if 1 or more of the following criteria are met:

  1. Therapy with clopidogrel within the last 12 months.
  2. Any history of prior treatment with aspirin which has resulted in a significant clinical adverse event requiring the discontinuation of aspirin therapy (e.g. bleeding, GI intolerance, etc. or intolerance to aspirin.
  3. Patients requiring anticoagulation treatment with warfarin, heparin or low molecular weight heparin for any medical condition.
  4. Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her physician immediately.
  5. History of a major bleeding event (requiring blood transfusion or hospitalization, bleeding at a critical site, or life-threatening).
  6. Clinical indication for the use of clopidogrel and/or a different antithrombotic regimen.
  7. History of active substance or alcoholic abuse within the last year.
  8. Known hypersensitivity or contraindication to study treatments.
  9. Chronic viral hepatitis or chronic liver disease from any other cause associated with a MELD score equal to or higher than 8.
  10. Presence of any disease (e.g. cancer) that is likely to significantly shorten life expectancy.
  11. > 81 years of age
  12. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  13. A history of gastrointestinal bleeding in the last 12 months.
  14. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days, or anticipation of the need for major surgical procedure during the course of the study.
  15. Biopsy or other minor surgical procedure, excluding placement of a vascular access device or bone marrow biopsy, within 7 days prior to study enrollment.
  16. Ongoing serious, non-healing wound, ulcer, or bone fracture.
  17. Treatment with a CYP3A4 inhibitor, including azole antifungals (topicals are permitted); protease inhibitors; nefazodone; cyclosporine; erythromycin; clarithromycin; and troleandomycin.
  18. Serum AST greater than or equal to 2 x ULN Serum ALT greater than or equal 2 x ULN Total Bilirubin greater than or equal 2 X ULN Serum creatinine greater than or equal 1.5 X ULN
  19. Patients with a diagnosis of polycythemia vera > 5 years from the time of registration
  20. Patients who do not have high risk polycythemia vera as defined by experiencing a thrombotic event (see section 3.1) occurring since the initial diagnosis of PV.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00940784

Locations
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, New York
Mt. Sinai Medical Center
New York, New York, United States, 10029
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Myeloproliferative Disorders-Research Consortium
  More Information

No publications provided

Responsible Party: Raffaele Landolfi, MD, Myeloproliferative Disorders-Research Consortium
ClinicalTrials.gov Identifier: NCT00940784     History of Changes
Other Study ID Numbers: MPD-RC 108, P01 Ca 108671-01A2
Study First Received: July 14, 2009
Last Updated: June 24, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Aspirin
Ticlopidine
Clopidogrel
Hydroxyurea
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
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 25, 2014