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

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ClinicalTrials.gov Identifier: NCT00991939
Recruitment Status : Terminated (The study was closed due to accrual futility there were only a total of 8 subjects enrolled.)
First Posted : October 8, 2009
Results First Posted : February 14, 2014
Last Update Posted : February 14, 2014
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
New England Research Institutes

Tracking Information
First Submitted Date  ICMJE October 7, 2009
First Posted Date  ICMJE October 8, 2009
Results First Submitted Date  ICMJE January 2, 2014
Results First Posted Date  ICMJE February 14, 2014
Last Update Posted Date February 14, 2014
Study Start Date  ICMJE January 2010
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2009)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00991939 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2009)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry [ Time Frame: Through 60 days after study entry ]
  • 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 ]
  • 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 ]
  • 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 ]
  • The Percentage of Patients Undergoing Splenectomy [ Time Frame: 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 [ Time Frame: Weeks 4, 8, and 52 after study entry ]
  • The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score [ Time Frame: Through 365 days after study entry ]
  • The Percentage of Patients Not Completing Study Therapy [ Time Frame: 49 days after study entry ]
  • The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy [ Time Frame: Through 1 year after study entry ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2009)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry [ Time Frame: Through 60 days after study entry ]
  • 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 ]
  • 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 ]
  • 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 ]
  • The Percentage of Patients Undergoing Splenectomy [ Time Frame: 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 [ Time Frame: Weeks 4, 8, and 52 after study entry ]
  • The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score [ Time Frame: Through 365 days after study entry ]
  • The Percentage of Patients Not Completing Study Therapy [ Time Frame: 42 days after study entry ]
  • The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy [ Time Frame: Through 1 year after study entry ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Initial Treatment of Patients With Immune Thrombocytopenic Purpura
Official Title  ICMJE Initial Treatment of Patients With Immune Thrombocytopenic Purpura: The ITP^2 Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Immune Thrombocytopenic Purpura
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: High dose pulse dexamethasone
    Intervention: Drug: Dexamethasone USP Micronized
  • Active Comparator: Standard prednisone therapy
    Intervention: Drug: Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 11, 2013)
8
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2009)
140
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00991939
Other Study ID Numbers  ICMJE 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
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party New England Research Institutes
Study Sponsor  ICMJE New England Research Institutes
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
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 Boston Children’s Hospital
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, College Park
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
PRS Account New England Research Institutes
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP