Initial Treatment of Patients With Immune Thrombocytopenic Purpura

NCT ID: NCT00991939

Last Updated: 2014-02-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-03-31

Brief Summary

This study will compare treatment with 3 courses of high-dose dexamethasone versus treatment with prednisone, for patients recently diagnosed with immune thrombocytopenic purpura (ITP). The primary hypothesis is that patients treated with high-dose dexamethasone will obtain a more durable remission than patients treated with prednisone.

Detailed Description

ITP is a common disorder associated with significant morbidity. For more than 40 years it has been recognized that this disorder was responsive to corticosteroid therapy. As corticosteroids are easily obtainable and inexpensive, they have become the standard first-line therapy for adult patients with newly-diagnosed ITP. Generally, patients are treated with prednisone at a dose of approximately 1 mg/kg, or 60 mg/day, and once a response is obtained the daily dosage is gradually tapered. While approximately 70% of patients treated in this manner respond initially, most will relapse as the corticosteroid dose is lowered; ultimately only 15-20% of patients achieve a complete or partial remission of their ITP at an "acceptable" dose of prednisone. Recently, several studies have suggested that the use of high dose corticosteroids, specifically pulse dexamethasone, may be a more efficacious initial therapy for ITP, capable of causing a higher initial response rate and a significantly longer duration of remission despite a shorter course of initial therapy.

This study will compare treatment with 3 courses of high-dose dexamethasone versus treatment with prednisone, for patients recently diagnosed with immune thrombocytopenic purpura (ITP). The primary hypothesis is that patients treated with high-dose dexamethasone will obtain a more durable remission than patients treated with standard oral corticosteroids. This may reflect the ability of high dose corticosteroids to eradicate a sensitive pathogenic lymphoid clone that may be transiently susceptible to aggressive immunosuppressive therapy early in the course of disease.

Conditions

Immune Thrombocytopenic Purpura

Study Design

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

Study Groups

High dose pulse dexamethasone

Group Type: EXPERIMENTAL

Dexamethasone USP Micronized

Intervention Type: DRUG

The dose for dexamethasone is 30 mg/day for patients \< 60 kg and 40 mg/day for patients \> 60 kg. The patient will be dosed on days 1-4, 15-18 and 29-32. On the remaining days during the treatment phase of the study, the patient will receive placebo capsules.

Standard prednisone therapy

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

Prednisone will be administered to study patients at a dose of 60 mg/day for patients less than 60 kg and 80 mg/day for patients \> 60 kg for 21 days. The following schedule for tapering of prednisone will be used: after three weeks of treatment at either 60 mg/day (for patients \< 60 kg) or 80 mg/day (for patients ≥ 60 kg), the dose will be reduced to 40 mg/day for 1 week, then 20 mg/day for 1 week, then 10 mg/day for 1 week, then 5 mg/day for 1 week and then stopped. Placebo capsules will be added as necessary during the treatment phase of the study, to maintain blinding.

Interventions

Dexamethasone USP Micronized

The dose for dexamethasone is 30 mg/day for patients \< 60 kg and 40 mg/day for patients \> 60 kg. The patient will be dosed on days 1-4, 15-18 and 29-32. On the remaining days during the treatment phase of the study, the patient will receive placebo capsules.

Intervention Type: DRUG

Prednisone

Prednisone will be administered to study patients at a dose of 60 mg/day for patients less than 60 kg and 80 mg/day for patients \> 60 kg for 21 days. The following schedule for tapering of prednisone will be used: after three weeks of treatment at either 60 mg/day (for patients \< 60 kg) or 80 mg/day (for patients ≥ 60 kg), the dose will be reduced to 40 mg/day for 1 week, then 20 mg/day for 1 week, then 10 mg/day for 1 week, then 5 mg/day for 1 week and then stopped. Placebo capsules will be added as necessary during the treatment phase of the study, to maintain blinding.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Must meet criteria for a diagnosis of ITP as specified by ASH guidelines
• Must be within 30 days after diagnosis of ITP at the time of randomization (diagnosis of ITP starts with first platelet count ≤ 100,000/μl)
• Platelet count ≤ 30,000/μl at the time ITP is diagnosed, and/or at some time between the diagnosis of ITP and study entry
• Platelet count ≤ 150,000/μl at the time of randomization
• Age ≥ 15 years
• If bone marrow examination is available, it must be compatible with ITP
• Subjects, or their legal guardians, must have the ability to provide informed consent

Exclusion Criteria

• Rituximab therapy or splenectomy for ITP or for any other cause within the previous 8 weeks.
• Known HIV infection
• Known HCV infection
• Known systemic lupus erythematosus
• Pregnancy or breastfeeding
• Insulin-requiring diabetes mellitus
• Previous exposure to prednisone for ITP at a dose ≥ 1.5 mg/kg prednisone/day for ≥ 1 week prior to study entry
• Ongoing use of treatments that are known to inhibit platelet function, e.g. aspirin
• Anything that in the opinion of the investigator is likely to interfere with participation in the study
• Persons previously randomized in the ITP^2 study
• Persons currently enrolled in other interventional clinical trials
• Exposure to thrombopoietic agent prior to study entry
• Previous exposure to dexamethasone for the treatment of ITP at a dose of 30 mg/day or greater for subjects < 60 kg or 40 mg/day or greater for subjects >= 60 kg for at least four days

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Carelon Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan F Assmann, PhD

Role: PRINCIPAL_INVESTIGATOR

Carelon Research

James Bussel, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College, Cornell University

Alvin Schmaier, MD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University

Jodi Segal, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Terry Gernsheimer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Eliot Williams, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Ellis Neufeld, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Judith Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Thomas Ortel, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

David Kuter, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Cindy Leissinger, MD

Role: PRINCIPAL_INVESTIGATOR

Tulane University

Ann Zimrin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland

Nigel Key, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

James George, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Oklahoma

Michele Lambert, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Joseph Kiss, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Bruce Sachais, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Tulane University

New Orleans, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

Children's Hospital Boston

Boston, Massachusetts, United States

Weill Medical College, Cornell University

New York, New York, United States

University of North Carolina Hospitals

Chapel Hill, North Carolina, United States

Duke University

Durham, North Carolina, United States

Case Western Reserve University

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

The University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Presbyterian and Shadyside Hospital

Pittsburgh, Pennsylvania, United States

University of Washington Medical Center

Seattle, Washington, United States

Gundersen Clinic

La Crosse, Wisconsin, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

U01HL072268

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HL072268

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HL072033

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675

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Identifier Source: org_study_id