Clopidogrel and Aspirin for the Treatment of Polycythemia Vera

NCT ID: NCT00940784

Last Updated: 2014-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2011-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Polycythemia Vera

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Clopidogrel

Subjects will be randomized to clopidogrel (oral-75 mg per day) in addition to low dose aspirin and hydroxyurea

Group Type EXPERIMENTAL

Clopidogrel (Plavix)

Intervention Type DRUG

Clopidogrel, aspirin plus hydroxyurea 75mg qd (Plavix) + 81 - 100 mg qd (aspirin) + hydroxyurea

Aspirin

Intervention Type DRUG

81-100 mg qd

Placebo

Subjects will be randomized placebo in addition to low dose aspirin and hydroxyurea

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo, aspirin (81-100 mg qd) plus hydroxyurea

Aspirin

Intervention Type DRUG

81-100 mg qd

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Clopidogrel (Plavix)

Clopidogrel, aspirin plus hydroxyurea 75mg qd (Plavix) + 81 - 100 mg qd (aspirin) + hydroxyurea

Intervention Type DRUG

Placebo

Placebo, aspirin (81-100 mg qd) plus hydroxyurea

Intervention Type DRUG

Aspirin

81-100 mg qd

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Plavix

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

81 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Myeloproliferative Disorders-Research Consortium

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Ronald Hoffman

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Ronald Hoffman

Professor of Medicine, Hematology and Medical Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ronald Hoffman, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

P01CA108671-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MPD-RC 108

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 07-0548-00108

Identifier Type: -

Identifier Source: org_study_id