Different Ribavirin Dosages and Different Duration of Treatment in Combination With PegInterferon in Patients With Genotype 2 and 3 (WRITE)

Chronic Hepatitis Clinical Trial

— WRITE  

Official title:

RCT Comparing Different Ribavirin Dosages and Durations of Treatment in Combination With Peginterferon in HCV Genotypes 2 and 3 (WRITE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01380938
• Other study ID #: EPAT-01-2010
• Status: Completed
• Phase: Phase 3
• Start date: December 1, 2018
• Est. completion date: November 30, 2019

Study information

• Verified date: March 2022
• Source: Casa Sollievo della Sofferenza IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1150
• Est. completion date: November 30, 2019
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis
• Hepatitis, Chronic

Intervention

Drug:
• Peginterferon alpha-2a + Ribavirin
Administration of ribavirin at a dosage of 1000 or 1200 mg per day based on body weight < or > 75 kg for 24 weeks (Arm A). Treatment duration of 48 weeks with standard fixed dose of ribavirin (800 mg/day) (Arm B). These schedules will be compared with diagram of standard therapy with 800 mg daily of ribavirin for 24 weeks (Arm C)

Locations

Country	Name	City	State
Italy	Infectious Diseases Unit	Avellino
Italy	Clinical Medicine Unit "Mater Dei"	Bari
Italy	Università di Bari	Bari
Italy	Medicine Unit	Barletta
Italy	Infectious Diseases Unit "V. Emanuele"	Bisceglie
Italy	Medicine Unit	Canosa di Puglia
Italy	Hepatology Unit	Casarano
Italy	IRCCS "De Bellis"	Castellana
Italy	Hepatology Unit	Catania
Italy	Infectious Diseases Unit	Catania
Italy	Gastroenterology Unit	Como
Italy	Gastroenterology Unit Arcispedale "S. Anna"	Ferrara
Italy	Gastroenterology Unit	Firenze
Italy	Internal Medicine University of Firenze	Firenze
Italy	Gastroenterology Unit	Foggia
Italy	Infectious Diseases	Foggia
Italy	Gastroenterology Unit	Galatina
Italy	Infectious Diseases	Lucca
Italy	Gastroenterology Unit	Mottola
Italy	Gastroenterology Unit "Cardarelli"	Napoli
Italy	USL Napoli 1	Napoli
Italy	Hospital "V. Cervello"	Palermo
Italy	Medical Clinic University of Palermo	Palermo
Italy	Infectious Diseases Unit IRCCS "San Matteo"	Pavia
Italy	Campus Biomedico University	Roma
Italy	Hepatology Unit "S. Pertini"	Roma
Italy	Hepatology Unit "san Camillo"	Roma
Italy	Ospedale "Villa Betania"	Roma
Italy	IRCCS "L. Spallanzani"	Rome
Italy	IRCCS "Casa Sollievo della Sofferenza"	San Giovanni Rotondo
Italy	Infectious Diseases Unit Ospedale Civile	Sassari
Italy	Medicine Unit	Sassari
Italy	Infectious Diseases	Siracusa
Italy	SS. Annunziata	Taranto
Italy	Medicine Unit	Venosa

Sponsors (32)

Lead Sponsor

Collaborator

Casa Sollievo della Sofferenza IRCCS

Arcispedale S. Anna, Ferrara, Azienda Ospedaliera V. Cervello, Azienda Ospedaliera, Lucca, Azienda Ospedaliera, Siracusa, Azienda Ospedaliero Universitaria di Sassari, Azienda Ospedaliero-Universitaria Careggi, Azienda Ospedaliero-Universitaria, Catania, Campus Bio-Medico University, Cardarelli Hospital, Casa di Cura Mater Dei, IRCCS De Bellis, Castellana, IRCCS L. Spallanzani, IRCCS Policlinico S. Matteo, Ospedale Civile Spirito Santo, Ospedale Civile Vittorio Emanuele II, Bisceglie, Ospedale di Canosa di Puglia, Ospedale di Mottola, Ospedale di Venosa, Ospedale Francesco Ferrari, Ospedale Monsignor R. Dimiccoli, Barletta, Ospedale San Giuseppe Moscati, Avellino, Ospedale Sandro Pertini, Roma, Ospedale Santa Caterina Novella, Galatina, Ospedale SS. Annunziata, Taranto, Ospedale Valduce, Como, Ospedali Riuniti di Foggia, San Camillo Hospital, Rome, University of Bari, University of Florence, University of Palermo, USL Napoli 1

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virological Response (SVR)	The primary measure of efficacy will be HCV RNA not detectable in serum samples 24 weeks after the end of therapy (SVR).	6 months after the end of treatment
Secondary	Rapid virological response (RVR)	proportion of patients with undetectable HCV RNA 4 weeks after the start of treatment	On treatment week 4