Initial Treatment of Patients With Immune Thrombocytopenic Purpura (ITP^2)

This study has been terminated.
(The study was closed due to accrual futility there were only a total of 8 subjects enrolled.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00991939
First received: October 7, 2009
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Immune Thrombocytopenic Purpura
Drug: Dexamethasone USP Micronized
Drug: Prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Initial Treatment of Patients With Immune Thrombocytopenic Purpura: The ITP^2 Study

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • The Percentage of Patients in Each Treatment Arm Who Remain Free of All ITP Therapy With a Platelet Count ≥ 50,000/μl From 60 Days Through 365 Days After Study Entry. [ Time Frame: From 60 days through 365 days after study entry. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Percentage of Patients Who Remain Free of All ITP Therapy With a Platelet Count ≥ 150,000/μl From 60 Days Through 365 Days After Study Entry [ Time Frame: From 60 days through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients With Platelets ≥ 50,000/μl at 365 Days Who Are Off All Treatment, Have Received ≤ 2 Acute Therapeutic Interventions for Thrombocytopenia, and Whose Last Acute Therapeutic Intervention Occurred at Least 90 Days Before Day 365 [ Time Frame: 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients Who Remain Free of All ITP Therapy With a Platelet Count of ≥ 150,000 From 180 Through 365 Days After Study Entry [ Time Frame: From 180 days through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients Who Remain Free of All ITP Therapy With a Platelet Count of ≥ 50,000 From 180 Through 365 Days After Study Entry [ Time Frame: From 180 days through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry [ Time Frame: Through 60 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients Receiving Acute Therapeutic Intervention Beyond the First 60 Days After Study Entry [ Time Frame: From 60 days through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Platelet Counts ≥ 50,000/μl After Day 60 (If a Subject Receives an Acute Therapeutic Intervention, the Next Protocol-specified Platelet Count Will be Excluded From This Analysis, as it May be Influenced by the Intervention.) [ Time Frame: From 60 days through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Platelet Counts ≥ 150,000/μl After Day 60 (If a Subject Receives an Acute Therapeutic Intervention, the Next Protocol-specified Platelet Count Will be Excluded From This Analysis, as it May be Influenced by the Intervention.) [ Time Frame: From 60 days through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients Undergoing Splenectomy [ Time Frame: Through 365 days after study entry ] [ Designated as safety issue: No ]
  • Change in the Quality of Life From Randomization to Weeks 4, 8 and End of Study, Determined Using the SF-36 Health Survey [ Time Frame: Weeks 4, 8, and 52 after study entry ] [ Designated as safety issue: No ]
  • The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score [ Time Frame: Through 365 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients Not Completing Study Therapy [ Time Frame: 49 days after study entry ] [ Designated as safety issue: No ]
  • The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy [ Time Frame: Through 1 year after study entry ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: January 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High dose pulse dexamethasone Drug: 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.
Active Comparator: Standard prednisone therapy 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.

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00991939

Locations
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
Weill Medical College, Cornell University
New York, New York, United States, 10021
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States, 27514
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Oklahoma
The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Presbyterian and Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
United States, Wisconsin
Gundersen Clinic
La Crosse, Wisconsin, United States, 54601
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
New England Research Institutes
Investigators
Principal Investigator: Susan F Assmann, PhD New England Research Institutes
Principal Investigator: James Bussel, MD Weill Medical College, Cornell University
Principal Investigator: Alvin Schmaier, MD Case Western Reserve University
Principal Investigator: Jodi Segal, MD Johns Hopkins University
Principal Investigator: Terry Gernsheimer, MD University of Washington
Principal Investigator: Eliot Williams, MD University of Wisconsin, Madison
Principal Investigator: Ellis Neufeld, MD Children's Hospital Boston
Principal Investigator: Judith Lin, MD Brigham and Women's Hospital
Principal Investigator: Thomas Ortel, MD Duke University
Principal Investigator: David Kuter, MD Massachusetts General Hospital
Principal Investigator: Cindy Leissinger, MD Tulane University
Principal Investigator: Ann Zimrin, MD University of Maryland
Principal Investigator: Nigel Key, MD University of North Carolina, Chapel Hill
Principal Investigator: James George, MD The University of Oklahoma
Principal Investigator: Michele Lambert, MD Children's Hospital of Philadelphia
Principal Investigator: Joseph Kiss, MD University of Pittsburgh
Principal Investigator: Bruce Sachais, MD, PhD University of Pennsylvania
  More Information

No publications provided

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00991939     History of Changes
Other Study ID Numbers: 675, U01HL072268, HL072268, HL072033, HL072291, HL072196, HL072289, HL072248, HL072191, HL072299, HL072305, HL072274, HL072028, HL072359, HL072072, HL072355, HL072283, HL072346, HL072331, HL072290
Study First Received: October 7, 2009
Results First Received: January 2, 2014
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New England Research Institutes:
Immune thrombocytopenic purpura
ITP
Dexamethasone
Prednisone

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 22, 2014