Clinical trial NCT01380938: Different Ribavirin Dosages and Different Duration of Treatment in Combination With PegInterferon in Patients With Genotype 2 and 3 (WRITE)
Official title: RCT Comparing Different Ribavirin Dosages and Durations of Treatment in Combination With Peginterferon in HCV Genotypes 2 and 3 (WRITE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis
Keywords: genotypes 2 and 3
combination treatment
individualized treatment
Lead sponsor: Casa Sollievo della Sofferenza IRCCS
Sponsor class: OTHER
Collaborators: name: Casa di Cura Mater Dei
name: IRCCS L. Spallanzani
name: Ospedale Francesco Ferrari
name: Azienda Ospedaliero Universitaria di Sassari
name: Fondazione IRCCS Policlinico San Matteo di Pavia
name: Arcispedale S. Anna, Ferrara
name: Azienda Ospedaliero-Universitaria, Catania
name: Ospedale di Venosa
name: Ospedale Monsignor R. Dimiccoli, Barletta
name: IRCCS De Bellis, Castellana
name: USL Napoli 1
name: Ospedale San Giuseppe Moscati, Avellino
name: Cardarelli Hospital
name: Ospedale Civile Vittorio Emanuele II, Bisceglie
name: Azienda Ospedaliero-Universitaria Careggi
name: Azienda Ospedaliera V. Cervello
name: Ospedale Civile Spirito Santo
name: Ospedale di Canosa di Puglia
name: University of Palermo
name: San Camillo Hospital, Rome
name: Campus Bio-Medico University
name: Ospedale Sandro Pertini, Roma
name: Ospedali Riuniti di Foggia
name: Ospedale SS. Annunziata, Taranto
name: Ospedale di Mottola
name: Ospedale Santa Caterina Novella, Galatina
name: University of Florence
name: Ospedale Valduce, Como
name: University of Bari
name: Azienda Ospedaliera, Siracusa
name: Azienda Ospedaliera, Lucca
First posted: 2011-06-27
Enrollment: 1150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: WRITE study aim at identifying the effectiveness of an innovative individualized schedule of treatment as compared to standard regimen in patients with chronic HCV genotype 2 and 3.

Detailed description: The investigators are going to compare weight-based dosages of ribavirin, in combination with Peginterferon alpha-2a, with standard fixed dosages of 800 mg. Patients will be evaluated at week 4 with an assay of sensitivity of 15 IU/ml. Patients with week 4 response will discontinue treatment at week 12 in both arms. Patients with HCV RNA still detectable at week 4 and receiving 1000-1200 mg of ribavirin in arm A will discontinue treatment at week 24, whereas patients with HCV RNA still detectable at week 4 and receiving 800 mg of ribavirin in arm B will be treated till week 48.

A standard treatment arm (C) including patients treated for 24 weeks with Peginterferon alpha-2a and fixed 800 mg ribavirin dosage will be used as control arm.

Eligibility criteria: Inclusion Criteria:

* Patients with chronic hepatitis C virus (HCV) infection (both HCVAb and HCV RNA positive)
* Patients with HCV genotype 2 or 3
* Age 18-70 years
* Naïve patients or previously treated only with standard interferon monotherapy
* Female patients of childbearing age who agree to avoid pregnancy during the period of treatment and 24 weeks after the end of treatment

Exclusion Criteria:

* Previous treatment with ribavirin
* Cirrhosis (CHILD PUGH B and C)
* Evidence of Hepatocellular carcinoma
* Pregnancy
* Retinopathy class I or II
* Alcohol consumption \> 40 gr/day
* Chronic cardiac or respiratory diseases
* HIV or HBsAg or HDV positivity
* Hemoglobin \< 8.5 gr/dL
* WBC \< 3.500/mm3
* PLT \< 80.000/mm3

Primary outcomes:
measure: Sustained virological Response (SVR)
timeFrame: 6 months after the end of treatment
Secondary outcomes:
measure: Rapid virological response (RVR)
timeFrame: On treatment week 4
Other outcomes:
Locations:
city: Avellino
country: Italy
facility: Infectious Diseases Unit
city: Bari
country: Italy
facility: Clinical Medicine Unit "Mater Dei"
city: Bari
country: Italy
facility: Università di Bari
city: Barletta
country: Italy
facility: Medicine Unit
city: Bisceglie
country: Italy
facility: Infectious Diseases Unit "V. Emanuele"
city: Canosa di Puglia
country: Italy
facility: Medicine Unit
city: Casarano
country: Italy
facility: Hepatology Unit
city: Castellana
country: Italy
facility: IRCCS "De Bellis"
city: Catania
country: Italy
facility: Hepatology Unit
city: Catania
country: Italy
facility: Infectious Diseases Unit
city: Como
country: Italy
facility: Gastroenterology Unit
city: Ferrara
country: Italy
facility: Gastroenterology Unit Arcispedale "S. Anna"
city: Firenze
country: Italy
facility: Gastroenterology Unit
city: Firenze
country: Italy
facility: Internal Medicine University of Firenze
city: Foggia
country: Italy
facility: Gastroenterology Unit
city: Foggia
country: Italy
facility: Infectious Diseases
city: Galatina
country: Italy
facility: Gastroenterology Unit
city: Lucca
country: Italy
facility: Infectious Diseases
city: Mottola
country: Italy
facility: Gastroenterology Unit
city: Napoli
country: Italy
facility: Gastroenterology Unit "Cardarelli"
city: Napoli
country: Italy
facility: USL Napoli 1
city: Palermo
country: Italy
facility: Hospital "V. Cervello"
city: Palermo
country: Italy
facility: Medical Clinic University of Palermo
city: Pavia
country: Italy
facility: Infectious Diseases Unit IRCCS "San Matteo"
city: Roma
country: Italy
facility: Campus Biomedico University
city: Roma
country: Italy
facility: Hepatology Unit "S. Pertini"
city: Roma
country: Italy
facility: Hepatology Unit "san Camillo"
city: Roma
country: Italy
facility: Ospedale "Villa Betania"
city: Rome
country: Italy
facility: IRCCS "L. Spallanzani"
city: San Giovanni Rotondo
country: Italy
facility: IRCCS "Casa Sollievo della Sofferenza"
city: Sassari
country: Italy
facility: Infectious Diseases Unit Ospedale Civile
city: Sassari
country: Italy
facility: Medicine Unit
city: Siracusa
country: Italy
facility: Infectious Diseases
city: Taranto
country: Italy
facility: SS. Annunziata
city: Venosa
country: Italy
facility: Medicine Unit
Study officials:
affiliation: IRCCS "Casa Sollievo della Sofferenza"
name: Alessandra Mangia, MD
role: STUDY_DIRECTOR
References:
citation: Mangia A, Dalgard O, Minerva N, Verbaan H, Bacca D, Ring-Larsen H, Copetti M, Carretta V, Piazzolla V, Cozzolongo R, Mottola L, Andriulli A. Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg-interferon alpha-2b and ribavirin. Aliment Pharmacol Ther. 2010 Jun;31(12):1346-53. doi: 10.1111/j.1365-2036.2010.04290.x. Epub 2010 Mar 8.
citation: Mangia A, Minerva N, Bacca D, Cozzolongo R, Agostinacchio E, Sogari F, Scotto G, Vinelli F, Ricci GL, Romano M, Carretta V, Petruzzellis D, Andriulli A. Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection. Hepatology. 2009 Feb;49(2):358-63. doi: 10.1002/hep.22679.
citation: Andriulli A, Mangia A, Iacobellis A, Ippolito A, Leandro G, Zeuzem S. Meta-analysis: the outcome of anti-viral therapy in HCV genotype 2 and genotype 3 infected patients with chronic hepatitis. Aliment Pharmacol Ther. 2008 Aug 15;28(4):397-404. doi: 10.1111/j.1365-2036.2008.03763.x. Epub 2008 Jun 11.
citation: Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17. doi: 10.1056/NEJMoa042608.