search
Back to results

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

Primary Purpose

Chronic Hepatitis

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Peginterferon alpha-2a + Ribavirin
Sponsored by
Casa Sollievo della Sofferenza IRCCS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis focused on measuring genotypes 2 and 3, combination treatment, individualized treatment

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Infectious Diseases Unit
  • Clinical Medicine Unit "Mater Dei"
  • Università di Bari
  • Medicine Unit
  • Infectious Diseases Unit "V. Emanuele"
  • Medicine Unit
  • Hepatology Unit
  • IRCCS "De Bellis"
  • Hepatology Unit
  • Infectious Diseases Unit
  • Gastroenterology Unit
  • Gastroenterology Unit Arcispedale "S. Anna"
  • Gastroenterology Unit
  • Internal Medicine University of Firenze
  • Gastroenterology Unit
  • Infectious Diseases
  • Gastroenterology Unit
  • Infectious Diseases
  • Gastroenterology Unit
  • Gastroenterology Unit "Cardarelli"
  • USL Napoli 1
  • Hospital "V. Cervello"
  • Medical Clinic University of Palermo
  • Infectious Diseases Unit IRCCS "San Matteo"
  • Campus Biomedico University
  • Hepatology Unit "S. Pertini"
  • Hepatology Unit "san Camillo"
  • Ospedale "Villa Betania"
  • IRCCS "L. Spallanzani"
  • IRCCS "Casa Sollievo della Sofferenza"
  • Infectious Diseases Unit Ospedale Civile
  • Medicine Unit
  • Infectious Diseases
  • SS. Annunziata
  • Medicine Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Arm C. Standard duration

Arm A

Arm B

Arm Description

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.

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)

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)

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Rapid virological response (RVR)
proportion of patients with undetectable HCV RNA 4 weeks after the start of treatment

Full Information

First Posted
June 23, 2011
Last Updated
March 9, 2022
Sponsor
Casa Sollievo della Sofferenza IRCCS
Collaborators
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
search

1. Study Identification

Unique Protocol Identification Number
NCT01380938
Brief Title
Different Ribavirin Dosages and Different Duration of Treatment in Combination With PegInterferon in Patients With Genotype 2 and 3 (WRITE)
Acronym
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

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
December 1, 2018 (Actual)
Primary Completion Date
November 30, 2019 (Actual)
Study Completion Date
November 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Casa Sollievo della Sofferenza IRCCS
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis
Keywords
genotypes 2 and 3, combination treatment, individualized treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
1150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm C. Standard duration
Arm Type
No Intervention
Arm Description
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.
Arm Title
Arm A
Arm Type
Experimental
Arm Description
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)
Arm Title
Arm B
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Peginterferon alpha-2a + Ribavirin
Other Intervention Name(s)
Peginterferon alpha-2a (40 kD) PEGASYS, Copegus or Rebetol, Ribavirin Teva
Intervention Description
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)
Primary Outcome Measure Information:
Title
Sustained virological Response (SVR)
Description
The primary measure of efficacy will be HCV RNA not detectable in serum samples 24 weeks after the end of therapy (SVR).
Time Frame
6 months after the end of treatment
Secondary Outcome Measure Information:
Title
Rapid virological response (RVR)
Description
proportion of patients with undetectable HCV RNA 4 weeks after the start of treatment
Time Frame
On treatment week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alessandra Mangia, MD
Organizational Affiliation
IRCCS "Casa Sollievo della Sofferenza"
Official's Role
Study Director
Facility Information:
Facility Name
Infectious Diseases Unit
City
Avellino
Country
Italy
Facility Name
Clinical Medicine Unit "Mater Dei"
City
Bari
Country
Italy
Facility Name
Università di Bari
City
Bari
Country
Italy
Facility Name
Medicine Unit
City
Barletta
Country
Italy
Facility Name
Infectious Diseases Unit "V. Emanuele"
City
Bisceglie
Country
Italy
Facility Name
Medicine Unit
City
Canosa di Puglia
Country
Italy
Facility Name
Hepatology Unit
City
Casarano
Country
Italy
Facility Name
IRCCS "De Bellis"
City
Castellana
Country
Italy
Facility Name
Hepatology Unit
City
Catania
Country
Italy
Facility Name
Infectious Diseases Unit
City
Catania
Country
Italy
Facility Name
Gastroenterology Unit
City
Como
Country
Italy
Facility Name
Gastroenterology Unit Arcispedale "S. Anna"
City
Ferrara
Country
Italy
Facility Name
Gastroenterology Unit
City
Firenze
Country
Italy
Facility Name
Internal Medicine University of Firenze
City
Firenze
Country
Italy
Facility Name
Gastroenterology Unit
City
Foggia
Country
Italy
Facility Name
Infectious Diseases
City
Foggia
Country
Italy
Facility Name
Gastroenterology Unit
City
Galatina
Country
Italy
Facility Name
Infectious Diseases
City
Lucca
Country
Italy
Facility Name
Gastroenterology Unit
City
Mottola
Country
Italy
Facility Name
Gastroenterology Unit "Cardarelli"
City
Napoli
Country
Italy
Facility Name
USL Napoli 1
City
Napoli
Country
Italy
Facility Name
Hospital "V. Cervello"
City
Palermo
Country
Italy
Facility Name
Medical Clinic University of Palermo
City
Palermo
Country
Italy
Facility Name
Infectious Diseases Unit IRCCS "San Matteo"
City
Pavia
Country
Italy
Facility Name
Campus Biomedico University
City
Roma
Country
Italy
Facility Name
Hepatology Unit "S. Pertini"
City
Roma
Country
Italy
Facility Name
Hepatology Unit "san Camillo"
City
Roma
Country
Italy
Facility Name
Ospedale "Villa Betania"
City
Roma
Country
Italy
Facility Name
IRCCS "L. Spallanzani"
City
Rome
Country
Italy
Facility Name
IRCCS "Casa Sollievo della Sofferenza"
City
San Giovanni Rotondo
ZIP/Postal Code
71013
Country
Italy
Facility Name
Infectious Diseases Unit Ospedale Civile
City
Sassari
Country
Italy
Facility Name
Medicine Unit
City
Sassari
Country
Italy
Facility Name
Infectious Diseases
City
Siracusa
Country
Italy
Facility Name
SS. Annunziata
City
Taranto
Country
Italy
Facility Name
Medicine Unit
City
Venosa
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
20222909
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.
Results Reference
background
PubMed Identifier
19072829
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.
Results Reference
background
PubMed Identifier
18549461
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.
Results Reference
background
PubMed Identifier
15972867
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs