Initial Treatment of Patients With Immune Thrombocytopenic Purpura

Immune Thrombocytopenic Purpura Clinical Trial

— ITP^2  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00991939
• Other study ID #: 675
• Secondary ID: U01HL072268HL072
• Status: Terminated
• Phase: Phase 3
• First received: October 7, 2009
• Last updated: January 2, 2014
• Start date: January 2010
• Est. completion date: March 2013

Study information

• Verified date: January 2014
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immune Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	Gundersen Clinic	La Crosse	Wisconsin
United States	University of Wisconsin	Madison	Wisconsin
United States	Tulane University	New Orleans	Louisiana
United States	Weill Medical College, Cornell University	New York	New York
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

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry		Through 60 days after study entry	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	The Percentage of Patients Undergoing Splenectomy		Through 365 days after study entry	No
Secondary	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	No
Secondary	The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score		Through 365 days after study entry	No
Secondary	The Percentage of Patients Not Completing Study Therapy		49 days after study entry	No
Secondary	The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy		Through 1 year after study entry	Yes