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

Nonneoplastic Condition Clinical Trial

— ITP0207  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00657410
• Other study ID #: ITP0207
• Secondary ID: GIMEMA-ITP-0207E
• Status: Completed
• Phase: Phase 3
• First received: April 11, 2008
• Last updated: February 17, 2017
• Start date: April 2008
• Est. completion date: February 2016

Study information

• Verified date: February 2017
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nonneoplastic Condition
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• dexamethasone

• prednisone

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
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	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	Milano
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	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Italy	UOC Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"	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	U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico	Tricase	(le)
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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final response (complete, partial, and minimal response) rate from evaluation of initial response		At day +180 from evaluation of initial response
Secondary	Initial response rate		At day 42 (arm I), at day 46 (arm II)
Secondary	Quality of response per arm		At initial evaluation and at final evaluation
Secondary	Final response rate		At day 180 from the statement of initial response
Secondary	Rate of bleeding events		At 3 years from study entry
Secondary	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
Secondary	Time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms		At 3 years from study entry
Secondary	Rate of persistent response		At 12 months from the statement of initial response
Secondary	Association of type of initial response with final and persistent response (in patients with final and persistent response)		At 3 years from study entry
Secondary	Rate of rescue interventions		After day 180 from evaluation of initial response
Secondary	Rate of splenectomy eligible patients		At 12 months from enrollment
Secondary	Rate of patients who have undergone splenectomy during follow-up		At 3 years from study entry
Secondary	Rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others) during follow-up		At 3 years from study entry