Initial Treatment of Patients With Immune Thrombocytopenic Purpura

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00991939

Acronym

ITP^2

Enrollment

Registered

2009-10-08

Start date

2010-01-31

Completion date

2013-03-31

Last updated

2014-02-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Immune Thrombocytopenic Purpura

Keywords

Immune thrombocytopenic purpura, ITP, Dexamethasone, Prednisone

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.

Interventions

DRUGDexamethasone 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.

DRUGPrednisone

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 design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

15 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

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

Measure	Time frame
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 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 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
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

Countries

United States

Participant flow

Participants by arm

Arm	Count
High Dose Pulse Dexamethasone 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.	5
Standard Prednisone Therapy 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.	3
Total	8

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Entire study terminated	4	1
Overall Study	Lost to Follow-up	0	1
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Standard Prednisone Therapy	High Dose Pulse Dexamethasone	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	0 Participants	2 Participants
Age, Categorical Between 18 and 65 years	1 Participants	5 Participants	6 Participants
Age, Continuous	62.5 years STANDARD_DEVIATION 35.8	37.2 years STANDARD_DEVIATION 15.6	46.7 years STANDARD_DEVIATION 26
Region of Enrollment United States	3 participants	5 participants	8 participants
Sex: Female, Male Female	1 Participants	3 Participants	4 Participants
Sex: Female, Male Male	2 Participants	2 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	5 / 5	3 / 3
serious Total, serious adverse events	3 / 5	1 / 3

Outcome results

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.

Time frame: From 60 days through 365 days after study entry.

Arm	Measure	Value (NUMBER)
High Dose Pulse Dexamethasone	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.	0 percentage of subjects
Standard Prednisone Therapy	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.	0 percentage of subjects

Comparison: Four subjects were not included in this analysis because not enough data was available to assess the primary outcome at the time the study was terminated.p-value: 195% CI: [-0.975, 0.708]Fisher Exact

Secondary