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

NCT ID: NCT00657410

Last Updated: 2017-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2016-02-29

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.

Conditions

Nonneoplastic Condition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM A - PDN

PDN 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.

Group Type: EXPERIMENTAL

prednisone

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

ARM B - DXM

DXM 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).

Group Type: EXPERIMENTAL

dexamethasone

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Interventions

dexamethasone

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent according to IGH/EU/GCP and national local laws
• Newly diagnosed untreated ITP adult patients
• Age > 18 < 80 years
• Platelet count <20x109/L
• Platelet count > 20 x109/L and <50x109/L plus bleeding with score > 8 (according to grading scale at paragraph 7.1)
• Baseline Quality of Life evaluation questionnaire filled in Newly diagnosed untreated ITP adult patients
• Age > 18 < 80 years
• Platelet count <20x109/L
• Platelet count > 20 x109/L and <50x109/L plus bleeding with score > 8 (according to grading scale at paragraph 7.1)
• Baseline Quality of Life evaluation questionnaire filled in

Exclusion Criteria

• Active malignancy at time of study entry
• Steroids administration (PDN <1mg/Kg/day) for more than 5 days before randomization
• Concomitant treatment with anti-platelet and or anti-coagulant drugs
• Concomitant severe psychiatric disorders
• Not confirmed diagnosis of ITP for

• *Positivity of autoimmunity markers: antinucleus (≥1:80), anti-tireoglobulin, anti-tireoperoxidase, anti-cardiolipin (≥ 40 GPL UmL), anti-b2glycoprotein (≥ 40 IgG U/mL) antibodies, Lupus Anticoagulant (KCT ratio, dRVVT ratios ≥1.5 times the upper normal limit ), direct antiglobulin test (DAT ).
• Presence of autoimmune hemolytic anemia
• Presence of connective tissue disease
• Women who are pregnant or breastfeeding
• Cardiovascular diseases requiring treatment
• Severe non-controlled, despite therapy, hypertension and diabetes
• Liver and kidney function impairment (creatinine, ALT, AST >2 times upper normal limit)
• HCVAb, HIVAb, HBsAg, HBcAb seropositive status
• Chronic liver disease
• Documented viral illness by the positivity of IgM, or vaccination both occurred one month before diagnosis
• Intake of drugs not previously taken within one week before diagnosis
• Bleeding score 15 due to ICH or to GI bleeding (according to grading scale at paragraph 7.1, Tab. 3)
• Active gastric ulcer.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Gabriella Mazzucconi, MD

Role: PRINCIPAL_INVESTIGATOR

Gruppo Italiano Malattie EMatologiche dell'Adulto

Locations

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 Piceno, , 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

Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile

Civitanova Marche, , Italy

U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza

Cosenza, , Italy

Ospedale Maggiore - Div.Medicina Crema

Crema, , Italy

Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria

Foggia, , Italy

Ospedale Santa Maria Goretti

Latina, , Italy

ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia

Lecce, , Italy

Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

Meldola, , Italy

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina

Messina, , Italy

Azienda Ospedaliera San Paolo - Unità di Ematologia e Trombosi

Milan, , Italy

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

Novara, , Italy

Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"

Palermo, , Italy

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, , Italy

Med. Int. ed Oncologia Medica IRCCS Policlinico S. Matteo

Pavia, , Italy

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza

Piacenza, , Italy

Pordenone Unità operativa Medicina II Az. Osp. S. M. degli Angeli

Pordenone, , Italy

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, , Italy

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

Reggio Calabria, , Italy

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Ospedale "Infermi"

Rimini, , Italy

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia

Roma, , Italy

Divisione di Ematologia - Ospedale S. Camillo

Roma, , Italy

Divisione Ematologia - Università Campus Bio-Medico

Roma, , Italy

UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"

Rome, , Italy

Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, , Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"

Siena, , Italy

Divisione di Ematologia dell' Università degli Studi di Torino - "Città della Salute e della Scienza di Torino"

Torino, , Italy

Struttura Complessa II Medicina - Ematologia - Centro di Riferimento Ematologico - Ospedale Maggiore

Trieste, , Italy

Clinica Ematologica - Policlinico Universitario

Udine, , Italy

Policlinico G. B. Rossi - Borgo Roma

Verona, , Italy

Ospedale San Bortolo

Vicenza, , Italy

Countries

Italy

References

Mazzucconi MG, Rodeghiero F, Avvisati G, De Stefano V, Gugliotta L, Ruggeri M, Vianelli N, Fazi P, Paoloni F, Sargentini V, Baldacci E, Ferretti A, Martino B, Vincelli ID, Carli G, Fortuna S, Di Ianni M, Ranalli P, Palandri F, Polverelli N, Lugli E, Rivolti E, Patriarca A, Rago A, D'Adda M, Gentile M, Siragusa S, Sibilla S, Carella AM, Rossi E, Battistini R, Zaja F, Bocchia M, Di Renzo N, Musto P, Crugnola M, Giuffrida AC, Krampera M, Tafuri A, Santoro C. Prednisone vs high-dose dexamethasone in newly diagnosed adult primary immune thrombocytopenia: a randomized trial. Blood Adv. 2024 Mar 26;8(6):1529-1540. doi: 10.1182/bloodadvances.2023010975.

Reference Type: DERIVED

PMID: 38231017 (View on PubMed)

Other Identifiers

GIMEMA-ITP-0207

Identifier Type: -

Identifier Source: secondary_id

Eudract 2008-000417-30

Identifier Type: -

Identifier Source: secondary_id

EU-20839

Identifier Type: -

Identifier Source: secondary_id

ITP0207

Identifier Type: -

Identifier Source: org_study_id