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

Initial Treatment of Patients With Immune Thrombocytopenic Purpura: The ITP^2 Study

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.

Study Overview

• Status: Terminated
• Conditions: Immune Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Dexamethasone USP Micronized; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College, Cornell University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Hospitals
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Presbyterian and Shadyside Hospital
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Clinic
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	From 60 days through 365 days after study entry.

Secondary Outcome Measures

Outcome Measure	Time Frame
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	From 60 days through 365 days after study entry
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	365 days after study entry
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	From 180 days through 365 days after study entry
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	From 180 days through 365 days after study entry
The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry	Through 60 days after study entry
The Percentage of Patients Receiving Acute Therapeutic Intervention Beyond the First 60 Days After Study Entry	From 60 days through 365 days after study entry
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.)	From 60 days through 365 days after study entry
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.)	From 60 days through 365 days after study entry
The Percentage of Patients Undergoing Splenectomy	Through 365 days after study entry
Change in the Quality of Life From Randomization to Weeks 4, 8 and End of Study, Determined Using the SF-36 Health Survey	Weeks 4, 8, and 52 after study entry
The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score	Through 365 days after study entry
The Percentage of Patients Not Completing Study Therapy	49 days after study entry
The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy	Through 1 year after study entry

Collaborators and Investigators

• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: 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: Eliot Williams, MD, University of Wisconsin, Madison; Principal Investigator: Thomas Ortel, MD, Duke University; Principal Investigator: James George, MD, The University of Oklahoma; Principal Investigator: Michele Lambert, MD, Children's Hospital of Philadelphia; Principal Investigator: Bruce Sachais, MD, PHD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: October 7, 2009
• First Submitted That Met QC Criteria: October 7, 2009
• First Posted (Estimate): October 8, 2009

Study Record Updates

• Last Update Posted (Estimate): February 14, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Dexamethasone; Prednisone; Immune thrombocytopenic purpura; ITP
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Prednisone
• Other Study ID Numbers: 675; U01HL072268 (U.S. NIH Grant/Contract); HL072268; HL072033; HL072291; HL072196; HL072289; HL072248; HL072191; HL072299; HL072305; HL072274; HL072028; HL072359; HL072072; HL072355; HL072283; HL072346; HL072331; HL072290

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No