Clinical trial NCT00657410: Prednisone or Dexamethasone in Newly Diagnosed, Previously Untreated Primary Immune Thrombocytopenic Purpura
Official title: Randomized Study of the Treatment of Primary Immune Thrombocytopenic Purpura (ITP) in Newly Diagnosed Untreated Adult Patients. Comparison of Standard Dose Prednisone Versus High-dose Dexamethasone.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nonneoplastic Condition
Keywords: idiopathic thrombocytopenic purpura
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2008-04-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Final response (complete, partial, and minimal response) rate from evaluation of initial response
timeFrame: At day +180 from evaluation of initial response
Secondary outcomes:
measure: Initial response rate
timeFrame: At day 42 (arm I), at day 46 (arm II)
measure: Quality of response per arm
timeFrame: At initial evaluation and at final evaluation
measure: Final response rate
timeFrame: At day 180 from the statement of initial response
measure: Rate of bleeding events
timeFrame: At 3 years from study entry
measure: 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)
timeFrame: At day 42 or before day 180 from the first evaluation
measure: Time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms
timeFrame: At 3 years from study entry
measure: Rate of persistent response
timeFrame: At 12 months from the statement of initial response
measure: Association of type of initial response with final and persistent response (in patients with final and persistent response)
timeFrame: At 3 years from study entry
measure: Rate of rescue interventions
timeFrame: After day 180 from evaluation of initial response
measure: Rate of splenectomy eligible patients
timeFrame: At 12 months from enrollment
measure: Rate of patients who have undergone splenectomy during follow-up
timeFrame: At 3 years from study entry
measure: Rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others) during follow-up
timeFrame: At 3 years from study entry
Other outcomes:
Locations:
city: Tricase
country: Italy
facility: U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico
state: (le)
city: Alessandria
country: Italy
facility: S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
city: Ancona
country: Italy
facility: Azienda ospedaliera Nuovo Ospedale "Torrette"
city: Arezzo
country: Italy
facility: USL 8 - Ospedale S.Donato
city: Ascoli
country: Italy
facility: Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
city: Bari
country: Italy
facility: UO Ematologia con trapianto- AOU Policlinico Consorziale di Bari
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Bologna
country: Italy
facility: University of Bologna Medical School
city: Brescia
country: Italy
facility: Sezione di Ematologia e Trapianti Spedali Civili
city: Busto Arsizio
country: Italy
facility: Struttura Complessa di Oncologia Medica - Azienda Ospedaliera - Ospedale di Circolo di Busto Arsizio
city: Civitanova - Marche
country: Italy
facility: Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile
city: Cosenza
country: Italy
facility: U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza
city: Crema
country: Italy
facility: Ospedale Maggiore - Div.Medicina Crema
city: Foggia
country: Italy
facility: Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
city: Latina
country: Italy
facility: Ospedale Santa Maria Goretti
city: Lecce
country: Italy
facility: ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
city: Milano
country: Italy
facility: Azienda Ospedaliera San Paolo - Unità di Ematologia e Trombosi
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
city: Palermo
country: Italy
facility: Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
city: Parma
country: Italy
facility: Cattedra di Ematologia CTMO Università degli Studi di Parma
city: Pavia
country: Italy
facility: Med. Int. ed Oncologia Medica IRCCS Policlinico S. Matteo
city: Pescara
country: Italy
facility: U.O. Ematologia Clinica - Azienda USL di Pescara
city: Piacenza
country: Italy
facility: Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
city: Pordenone
country: Italy
facility: Pordenone Unità operativa Medicina II Az. Osp. S. M. degli Angeli
city: Ravenna
country: Italy
facility: Dipartimento Oncologico - Ospedale S.Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
city: Reggio Emilia
country: Italy
facility: Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
city: Rimini
country: Italy
facility: Ospedale "Infermi"
city: Roma
country: Italy
facility: Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
city: Roma
country: Italy
facility: Divisione di Ematologia - Ospedale S. Camillo
city: Roma
country: Italy
facility: Divisione Ematologia - Università Campus Bio-Medico
city: Rome
country: Italy
facility: UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: San Giovanni Rotondo
country: Italy
facility: Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
city: Siena
country: Italy
facility: U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
city: Torino
country: Italy
facility: Divisione di Ematologia dell' Università degli Studi di Torino - "Città della Salute e della Scienza di Torino"
city: Trieste
country: Italy
facility: Struttura Complessa II Medicina - Ematologia - Centro di Riferimento Ematologico - Ospedale Maggiore
city: Udine
country: Italy
facility: Clinica Ematologica - Policlinico Universitario
city: Verona
country: Italy
facility: Policlinico G. B. Rossi - Borgo Roma
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
Study officials:
affiliation: Gruppo Italiano Malattie EMatologiche dell'Adulto
name: Maria Gabriella Mazzucconi, MD
role: PRINCIPAL_INVESTIGATOR
References: