Clinical trial NCT00991939: Initial Treatment of Patients With Immune Thrombocytopenic Purpura
Official title: Initial Treatment of Patients With Immune Thrombocytopenic Purpura: The ITP^2 Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Immune Thrombocytopenic Purpura
Keywords: Immune thrombocytopenic purpura
ITP
Dexamethasone
Prednisone
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-10-08
Enrollment: 8
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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.
timeFrame: From 60 days through 365 days after study entry.
Secondary outcomes:
measure: 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
timeFrame: From 60 days through 365 days after study entry
measure: 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
timeFrame: 365 days after study entry
measure: 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
timeFrame: From 180 days through 365 days after study entry
measure: 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
timeFrame: From 180 days through 365 days after study entry
measure: The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry
timeFrame: Through 60 days after study entry
measure: The Percentage of Patients Receiving Acute Therapeutic Intervention Beyond the First 60 Days After Study Entry
timeFrame: From 60 days through 365 days after study entry
measure: 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.)
timeFrame: From 60 days through 365 days after study entry
measure: 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.)
timeFrame: From 60 days through 365 days after study entry
measure: The Percentage of Patients Undergoing Splenectomy
timeFrame: Through 365 days after study entry
measure: Change in the Quality of Life From Randomization to Weeks 4, 8 and End of Study, Determined Using the SF-36 Health Survey
timeFrame: Weeks 4, 8, and 52 after study entry
measure: The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score
timeFrame: Through 365 days after study entry
measure: The Percentage of Patients Not Completing Study Therapy
timeFrame: 49 days after study entry
measure: The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy
timeFrame: Through 1 year after study entry
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: New York
country: United States
facility: Weill Medical College, Cornell University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Presbyterian and Shadyside Hospital
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: La Crosse
country: United States
facility: Gundersen Clinic
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Carelon Research
name: Susan F Assmann, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College, Cornell University
name: James Bussel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Alvin Schmaier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Jodi Segal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Terry Gernsheimer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Eliot Williams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Ellis Neufeld, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Judith Lin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Thomas Ortel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: David Kuter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tulane University
name: Cindy Leissinger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland
name: Ann Zimrin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Nigel Key, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Oklahoma
name: James George, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Michele Lambert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Joseph Kiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Bruce Sachais, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: