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Prednisone or Dexamethasone in Newly Diagnosed, Previously Untreated Primary Immune Thrombocytopenic Purpura

Phase 3
Completed
Conditions
Nonneoplastic Condition
Interventions
Procedure: quality-of-life assessment
Registration Number
NCT00657410
Lead Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
Brief Summary

RATIONALE: Drugs, such as prednisone and dexamethasone, may change the immune system and be an effective treatment for primary immune thrombocytopenic purpura. It is not yet known which drug is more effective in treating primary immune thrombocytopenic purpura.

PURPOSE: This randomized phase III trial is studying high-dose dexamethasone to see how well it works compared to standard-dose prednisone in treating patients with newly diagnosed, previously untreated primary immune thrombocytopenic purpura.

Detailed Description

OBJECTIVES:

Primary

* To evaluate the role of therapy intensification in adult patients with newly diagnosed, previously untreated primary immune thrombocytopenic purpura with high-dose dexamethasone (HD-DXM), in terms of improvement of response at 6 months after initial response, in comparison with standard-doses of prednisone.

Secondary

* Compare rate of initial response.

* Compare quality of response.

* Compare rate of final responses and rate of persistent response.

* Compare rate of bleeding events.

* Determine rate of resumed response with HD-DXM in non-responder patients or patients who have lost response (arm I only).

* Compare time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms.

* Compare rate of rescue interventions.

* Compare rate of eligible patients for splenectomy.

* Compare rate of patients who underwent splenectomy.

* Compare rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others).

* Compare patient's self reported quality of life.

OUTLINE: This is a multicenter study. Patients are stratified by treating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I (Standard-dose prednisone): Patients receive oral prednisone at a standard dose (1 mg/Kg) once daily on days 1-28 followed by a 14-day taper.

Patients considered non-responders at day 42 or who have lost response before evaluation of final response (day 180) are crossed to arm II.

* Arm II (High-dose dexamethasone): Patients receive oral dexamethasone at a high dose (40 mg/day) once daily on days 1-4. Treatment repeats every 14 days for 3 courses.

Quality of life is assessed at baseline, on day 42 (arm I) or 46 (arm II) (initial response evaluation day), 180 days after initial response evaluation, and at 3, 9, 12 months after randomization.

After completion of study treatment, patients are followed monthly until 1 year after randomization, every 2 months for 1 year, and then every 3 months for 1 year.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
150
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ARM B - DXMdexamethasoneDXM is administered orally at single fixed daily doses of 40 mg for 4 consecutive days, every 14 days, for 3 consecutive courses. If platelet count is £ 20x109/L or bleeding symptoms related to thrombocytopenia are present, lowdose DXM (0.035 mg/Kg/day) between courses is given. The patients (either from ARM A+B or from ARM B) considered NOT RESPONDER at day 46 or who HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be considered OFF TREATMENT. For these patients a second line therapy will be considered, according to the medical practice of the Centre (splenectomy or other).
ARM B - DXMquality-of-life assessmentDXM is administered orally at single fixed daily doses of 40 mg for 4 consecutive days, every 14 days, for 3 consecutive courses. If platelet count is £ 20x109/L or bleeding symptoms related to thrombocytopenia are present, lowdose DXM (0.035 mg/Kg/day) between courses is given. The patients (either from ARM A+B or from ARM B) considered NOT RESPONDER at day 46 or who HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be considered OFF TREATMENT. For these patients a second line therapy will be considered, according to the medical practice of the Centre (splenectomy or other).
ARM A - PDNquality-of-life assessmentPDN is administered orally at the daily dose of 1 mg/Kg for 4 consecutive weeks (from day 0 to day 28), then, therapy is tapered within 14 days. The patients considered NOT RESPONDER at day 42 or WHO HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be crossed to ARM B.
ARM A - PDNprednisonePDN is administered orally at the daily dose of 1 mg/Kg for 4 consecutive weeks (from day 0 to day 28), then, therapy is tapered within 14 days. The patients considered NOT RESPONDER at day 42 or WHO HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be crossed to ARM B.
Primary Outcome Measures
NameTimeMethod
Final response (complete, partial, and minimal response) rate from evaluation of initial responseAt day +180 from evaluation of initial response
Secondary Outcome Measures
NameTimeMethod
Initial response rateAt day 42 (arm I), at day 46 (arm II)
Quality of response per armAt initial evaluation and at final evaluation
Final response rateAt day 180 from the statement of initial response
Rate of bleeding eventsAt 3 years from study entry
Time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptomsAt 3 years from study entry
Rate of persistent responseAt 12 months from the statement of initial response
Association of type of initial response with final and persistent response (in patients with final and persistent response)At 3 years from study entry
Rate of patients who have undergone splenectomy during follow-upAt 3 years from study entry
Resumed response rate in non-responder patients (at day 42) or patients who have lost response before day 180 from the first evaluation (arm I only)At day 42 or before day 180 from the first evaluation
Rate of rescue interventionsAfter day 180 from evaluation of initial response
Rate of splenectomy eligible patientsAt 12 months from enrollment
Rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others) during follow-upAt 3 years from study entry

Trial Locations

Locations (42)

U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico

🇮🇹

Tricase, (le), Italy

S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo

🇮🇹

Alessandria, Italy

Azienda ospedaliera Nuovo Ospedale "Torrette"

🇮🇹

Ancona, Italy

USL 8 - Ospedale S.Donato

🇮🇹

Arezzo, Italy

Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"

🇮🇹

Ascoli, Italy

UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari

🇮🇹

Bari, Italy

Ospedali Riuniti di Bergamo

🇮🇹

Bergamo, Italy

University of Bologna Medical School

🇮🇹

Bologna, Italy

Sezione di Ematologia e Trapianti Spedali Civili

🇮🇹

Brescia, Italy

Struttura Complessa di Oncologia Medica - Azienda Ospedaliera - Ospedale di Circolo di Busto Arsizio

🇮🇹

Busto Arsizio, Italy

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U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico
🇮🇹Tricase, (le), Italy

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