Clopidogrel and Aspirin for the

Treatment of Polycythemia Vera

(ISCLAP)
This study is currently recruiting participants.
Verified by Myeloproliferative Disorders-Research Consortium, February 2010
First Received: July 14, 2009 Last Updated: February 24, 2010 History of
Changes

Myeloproliferative Disorders-Research
Sponsor:
Consortium

Information Myeloproliferative Disorders-Research

provided by: Consortium

ClinicalTrials.gov
NCT00940784
Identifier:

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) Phase II

Drug: Placebo
Drug: Aspirin

Study Interventional
Type:

Study Treatment, Randomized, Double Blind (Subject, Investigator),

Design: Placebo Control, Factorial Assignment, Safety/Efficacy Study

Official MPD-RC 108: Phase II, Randomized, Double-Blind, Placebo

Title: Controlled International Study of Clopidogrel and Aspirin for the
Treatment of Polycythemia Vera

Resource links provided by NLM:

Drug Information available for: Acetylsalicylic acid Clopidogrel

Clopidogrel Bisulfate

U.S. FDA Resources

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 July 2012

Date:

Estimated Primary July 2012 (Final data collection date for

Completion Date: primary outcome measure)
 Arms Assigned Interventions

Clopidogrel: Drug: Clopidogrel (Plavix)

Experimental Clopidogrel plus hydroxyurea 75mg qd + 81 100 mg
Clopidogrel plus qd + hydroxyurea
aspirin Drug: Aspirin

Placebo: Placebo Drug: Placebo Drug: Aspirin

Comparator
Aspirin plus placebo

Eligibility

Ages Eligible for Study: 18 Years to 81

Years
Genders Eligible for
Both
Study:
Accepts Healthy
No
Volunteers:
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:
o Hemoglobin >18.5 g/dl in men, >16.5 g/dl in women
or other evidence of increased red cell volume.
oPresence of JAK2V617F or other functionally similar
mutation such as JAK2 exon 12 mutation

Minor Criteria:
o Bone marrow biopsy showing hypercellularity for age
with trilineage growth (panmyelosis) with prominent
 erythroid, granulocyte, and megakaryocytic
proliferation.
o Serum erythropoietin level below the reference range
for normal.
o 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

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

Contacts
Contact: Raffaele +3096301543
rlandolfi@rm.unicatt.it
Landolfi, MD 35
Contact: Ronald ronald.hoffman@mssm.
212-241-1948
Hoffman, MD edu

Locations

United States, Illinois

University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Damiano Rondelli, MD 312-996-5820
drond@uic.edu
Principal Investigator: Damiano Rondelli, MD

United States, New York

Mt. Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Ronald Hoffman, MD 212-241-1948
ronald.hoffman@mssm.edu
Principal Investigator: Ronald Hoffman, MD
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Josef Prchal, MD 801-585-3229
Josef.prchal@hsc.utah.edu
Principal Investigator: Josef Prchal, MD
Sponsors and Collaborators
Myeloproliferative Disorders-Research Consortium
More Information

No publications provided

Responsible Party: Myeloproliferative Disorders-Research Consortium

( Raffaele Landolfi, MD )
Study ID Numbers: MPD-RC 108, P01 Ca 108671-01A2
Study First Received: July 14, 2009
Last Updated: February 24, 2010
ClinicalTrials.gov NCT00940784 History of Changes
Identifier:
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:

Polycythemia Hematologic Diseases
Anti-Inflammatory Agents Cyclooxygenase Inhibitors
Molecular Mechanisms of Myeloproliferative Disorders
Pharmacological Action Enzyme Inhibitors
Physiological Effects of Drugs Cardiovascular Agents
Hematologic Agents Pharmacologic Actions
Fibrinolytic Agents Analgesics, Non-Narcotic
Fibrin Modulating Agents Clopidogrel
Aspirin Platelet Aggregation Inhibitors
Sensory System Agents Peripheral Nervous System Agents
Therapeutic Uses Bone Marrow Diseases
Anti-Inflammatory Agents, Non- Antirheumatic Agents
Steroidal Central Nervous System Agents
Analgesics
Polycythemia Vera

ClinicalTrials.gov processed this record on March 14, 2010