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

• Sponsor: Casa Sollievo della Sofferenza IRCCS (Other)
• Overall Status: Completed
• CT.gov ID: NCT01380938
• Collaborator: Casa di Cura Mater Dei (Other), IRCCS L. Spallanzani (Other), Ospedale Francesco Ferrari (Other), Azienda Ospedaliero Universitaria di Sassari (Other), IRCCS Policlinico S. Matteo (Other), Arcispedale S. Anna, Ferrara (Other), Azienda Ospedaliero-Universitaria, Catania (Other), Ospedale di Venosa (Other), Ospedale Monsignor R. Dimiccoli, Barletta (Other), IRCCS De Bellis, Castellana (Other), USL Napoli 1 (Other), Ospedale San Giuseppe Moscati, Avellino (Other), Cardarelli Hospital (Other), Ospedale Civile Vittorio Emanuele II, Bisceglie (Other), Azienda Ospedaliero-Universitaria Careggi (Other), Azienda Ospedaliera V. Cervello (Other), Ospedale Civile Spirito Santo (Other), Ospedale di Canosa di Puglia (Other), University of Palermo (Other), San Camillo Hospital, Rome (Other), Campus Bio-Medico University (Other), Ospedale Sandro Pertini, Roma (Other), Ospedali Riuniti di Foggia (Other), Ospedale SS. Annunziata, Taranto (Other), Ospedale di Mottola (Other), Ospedale Santa Caterina Novella, Galatina (Other), University of Florence (Other), Ospedale Valduce, Como (Other), University of Bari (Other), Azienda Ospedaliera, Siracusa (Other), Azienda Ospedaliera, Lucca (Other)
• Enrollment: 1,150
• Locations: 35
• Arms: 3
• Actual Duration (Months): 12
• Patients Per Site: 32.9
• Patients Per Site Per Month: 2.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis	Drug: Peginterferon alpha-2a + Ribavirin	Phase 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: RCT Comparing Different Ribavirin Dosages and Durations of Treatment in Combination With Peginterferon in HCV Genotypes 2 and 3 (WRITE)
• Actual Study Start Date: Dec 1, 2018
• Actual Primary Completion Date: Nov 30, 2019
• Actual Study Completion Date: Nov 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Arm C. Standard duration Patients will be randomly assigned in 3:3:1 ratio to three treatment arms. In the standard treatment group (Arm C), patients will be treated for 24 weeks independently of the HCV RNA status at week 4 with Peginterferon alpha-2a at a dose of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 800 mg/day. Patients enrolled in Arm C will be treated for standard 24 weeks duration of treatment.
Experimental: Arm A Patients enrolled in Arm A will receive Peginterferon alpha-2a at a dosage of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 1000 mg/day for patients with a body weight < 75 kg or 1200 mg/day for those with a body weight > 75 kg. Patients with week 4 viral clearance (labelled as rapid virological responders, RVR) will be allocated to 12 week treatment duration (Arm A), whereas those without RVR will be treated for 24 weeks (Arm A)	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); Other Names: Peginterferon alpha-2a (40 kD) PEGASYS Copegus or Rebetol, Ribavirin Teva
Experimental: Arm B Patients enrolled in Arm B will receive Peginterferon alpha-2a at a dosage of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 800 mg/day. Patients with week 4 viral clearance (labelled as rapid virological responders, RVR) will be allocated to 12 week treatment duration (Arm B), whereas those without RVR will be treated for 48 weeks (Arm B)	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); Other Names: Peginterferon alpha-2a (40 kD) PEGASYS Copegus or Rebetol, Ribavirin Teva

Outcome Measures

Primary Outcome Measures

1. Sustained virological Response (SVR) [6 months after the end of treatment]

   The primary measure of efficacy will be HCV RNA not detectable in serum samples 24 weeks after the end of therapy (SVR).

Secondary Outcome Measures

1. Rapid virological response (RVR) [On treatment week 4]

   proportion of patients with undetectable HCV RNA 4 weeks after the start of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Infectious Diseases Unit	Avellino		Italy
2	Clinical Medicine Unit "Mater Dei"	Bari		Italy
3	Università di Bari	Bari		Italy
4	Medicine Unit	Barletta		Italy
5	Infectious Diseases Unit "V. Emanuele"	Bisceglie		Italy
6	Medicine Unit	Canosa di Puglia		Italy
7	Hepatology Unit	Casarano		Italy
8	IRCCS "De Bellis"	Castellana		Italy
9	Hepatology Unit	Catania		Italy
10	Infectious Diseases Unit	Catania		Italy
11	Gastroenterology Unit	Como		Italy
12	Gastroenterology Unit Arcispedale "S. Anna"	Ferrara		Italy
13	Gastroenterology Unit	Firenze		Italy
14	Internal Medicine University of Firenze	Firenze		Italy
15	Gastroenterology Unit	Foggia		Italy
16	Infectious Diseases	Foggia		Italy
17	Gastroenterology Unit	Galatina		Italy
18	Infectious Diseases	Lucca		Italy
19	Gastroenterology Unit	Mottola		Italy
20	Gastroenterology Unit "Cardarelli"	Napoli		Italy
21	USL Napoli 1	Napoli		Italy
22	Hospital "V. Cervello"	Palermo		Italy
23	Medical Clinic University of Palermo	Palermo		Italy
24	Infectious Diseases Unit IRCCS "San Matteo"	Pavia		Italy
25	Campus Biomedico University	Roma		Italy
26	Hepatology Unit "S. Pertini"	Roma		Italy
27	Hepatology Unit "san Camillo"	Roma		Italy
28	Ospedale "Villa Betania"	Roma		Italy
29	IRCCS "L. Spallanzani"	Rome		Italy
30	IRCCS "Casa Sollievo della Sofferenza"	San Giovanni Rotondo		Italy	71013
31	Infectious Diseases Unit Ospedale Civile	Sassari		Italy
32	Medicine Unit	Sassari		Italy
33	Infectious Diseases	Siracusa		Italy
34	SS. Annunziata	Taranto		Italy
35	Medicine Unit	Venosa		Italy

Sponsors and Collaborators

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

Investigators

• Study Director: Alessandra Mangia, MD, IRCCS "Casa Sollievo della Sofferenza"

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.

• Responsible Party: Alessandra Mangia, MD, Casa Sollievo della Sofferenza IRCCS
• ClinicalTrials.gov Identifier: NCT01380938
• Other Study ID Numbers: EPAT-01-2010
• First Posted: Jun 27, 2011
• Last Update Posted: Mar 24, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alessandra Mangia, MD, Casa Sollievo della Sofferenza IRCCS: genotypes 2 and 3; combination treatment; individualized treatment
• Additional relevant MeSH terms: Hepatitis, Chronic; Ribavirin; Peginterferon alfa-2a; Interferon-alpha

Study Results

No Results Posted as of Mar 24, 2022