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Efficacy and Safety of the Combination Vitamin D With Standard of Care in Egyptian Patients With Untreated Chronic Hepatitis C (ViZIR)

Primary Purpose

Chronic Hepatitis C

Status
Withdrawn
Phase
Phase 3
Locations
Egypt
Study Type
Interventional
Intervention
Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin
Sponsored by
ANRS, Emerging Infectious Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Hepatitis C - Genotype 4, SVR (Sustained Virological Response), Vitamin D, Treatment Naïve

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Common with National Program for Viral Hepatitis

  • Age: 18 years to 60 years
  • Positive HCV antibodies using a third generation test
  • Detectable HCV RNA by PCR
  • Liver biopsy showing chronic hepatitis with either a METAVIR score F1 with elevated liver enzymes or scores F2/F3
  • Naïve to treatment with PEG-IFN and RBV
  • HBs antigen negative
  • Prothrombin time ≥60 %, normal bilirubin, alpha-foeto protein < 3*normal range of the laboratory, anti-nuclear antibodies<1/160 Effective contraception during the treatment period; no breast-feeding

Specific to the trial

  • Prior approval from the Ministry of Health to be treated as part of the National Program with allocation to Peg-IFN α2b treatment
  • Living <100 km from Cairo and able to come to the centre every week for the treatment
  • Signed informed consent and willingness to participate in the trial
  • Naïve to treatment with vitamin D (received vitamin D less than 30 consecutive days in the 3 months preceding inclusion)
  • Biopsy slide validated by NHTMRI pathologist

Exclusion Criteria:

Common with National program for Viral Hepatitis

  • Serious co-morbid conditions such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes (HbA1C>8%) , chronic obstructive pulmonary disease
  • Major uncontrolled depressive illness
  • Solid transplant organ (renal, heart, or lung)
  • Untreated thyroid disease
  • History of previous anti-HCV therapy
  • Body mass index (BMI) greater than 30 kg/m²
  • Known human immunodeficiency virus (HIV) coinfection: although HIV testing will not be proposed or done, patients with known HIV coinfection will not be included in the trial
  • Anti-HCV therapy contraindications:
  • hypersensitivity to one of the two drugs (PEG-IFN, RBV)
  • pregnancy or unwilling to comply with adequate contraception
  • breast-feeding
  • neutropenia (<1500/mm3)
  • anaemia (<11g/dL for women ; <12g/dL for men)
  • thrombocytopenia (<100,000/mm3)
  • elevated creatinin (>1.5mg/dL)
  • concomitant liver disease other than hepatitis C (immuno-active chronic hepatitis B, autoimmune hepatitis, alcoholic liver disease, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease)
  • liver biopsy showing severe steatosis (>66%) and steatohepatitis; decompensated cirrhosis (Child Pugh>A); hepatocellular carcinoma, METAVIR score F4.
  • TSH>5 mU/L

Specific to the trial

  • Patients allocated to Peg-IFN alpha 2a treatment
  • Hypersensitivity to vitamin D
  • Vitamin D contraindications:
  • hypercalcaemia (fasting calcaemia >105 mg/L or 2.62 mmol/L)
  • ratio calciuria / creatininuria (fasting ratio >1 mmol Ca/mmol creatinin)
  • hyperphosphatemia (>1.5 mmol/L)
  • calcium lithiasis
  • patients being treated with thiazide diuretics (risk of hypercalcaemia with vitamin D treatment)
  • patients being treated with glucocorticoïds (decrease in vitamin D efficacy)
  • postmenopausal women treated by vitamin D and calcium for osteoporosis
  • Treatment by vitamin D more than 30 consecutive days in the 3 months preceding inclusion in the trial.

Sites / Locations

  • NHTMRI

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Vitamin D

Standard of Care

Arm Description

Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin

Pegylated Interferon Alpha 2b + Ribavirin

Outcomes

Primary Outcome Measures

Proportion of patients with Sustained Virological Response (SVR).
Proportion of patients with Sustained Virological Response (SVR) as defined by HCV RNA below the detection limit based on quantitative PCR 12 weeks after stopping treatment.

Secondary Outcome Measures

Rapid Virological Response (RVR)
HCV RNA at 4 weeks post initiation of combination therapy (PEG IFN + RBV)
Early Virological Response (EVR)
HCV RNA at 12 weeks post initiation of combination therapy
End of Treatment Response (ETR)
HCV RNA at end of treatment (week 48)
Normalization of ALT during treatment and 12 weeks after the end of treatment
Incidence of serious adverse events (SAE) grade 3 and 4 (ANRS scale)
incidence of SAE leading to dosage reduction or treatment cessation, percentage of patients treated by EPO and G-CSF
Evolution of FibroScan values between pre-inclusion and week 60

Full Information

First Posted
March 24, 2014
Last Updated
July 10, 2017
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Institut Pasteur
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1. Study Identification

Unique Protocol Identification Number
NCT02099604
Brief Title
Efficacy and Safety of the Combination Vitamin D With Standard of Care in Egyptian Patients With Untreated Chronic Hepatitis C
Acronym
ViZIR
Official Title
Efficacy and Safety of the Combination Vitamin D (Vit D), With Pegylated Interferon Alpha-2b (PEG-IFN)/Ribavirin (RBV) in Egyptian Patients With Untreated Chronic Hepatitis C: A Phase III Randomized Open-label Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Study objectives were considered as obsolete regarding the new AAD arrival
Study Start Date
April 2014 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Institut Pasteur

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to show the superiority of a 4 weeks lead-in phase of Vitamin D followed by a 48 weeks combination of Vitamin D with PEG-IFN plus RBV in comparison with standard PEG-IFN + RBV in untreated Egyptian patients with chronic hepatitis C, on the sustained virological response (SVR) at 3 months after end of treatment (week 60).
Detailed Description
- Method: Phase III, randomized, open-label superiority clinical trial, among Egyptian patients with chronic hepatitis C. - Treatment strategy: Vitamin D Arm: Vitamin D over a 4 weeks lead-in phase followed by Vitamin D in combination with PEG-INF plus RBV during 48 weeks. Standard of Care Arm: PEG-INF plus RBV during 48 weeks. - Main outcome: Proportion of patients with Sustained Virological Response (SVR) as defined by HCV RNA below the detection limit based on quantitative PCR 12 weeks after stopping treatment. Sample Size: 520 patients (260 per arm) Enrollment period: 12 months Patient's participation duration: 62 weeks (SOC Arm), 66 weeks (Vit-D Arm) Statistical analysis: The superiority of the vitamin D arm will be tested against the standard PEG IFN + RBV combination. 260 patients in each arm will give 80% power to document a 12% difference in the SVR rates between the experimental (Vitamin D) and the control (standard treatment) arms.. A futility analysis is planned for this study, in order to be able to interrupt the trial prematurely in case preliminary results show a lack of efficacy of vitamin D. This analysis will be performed on half of the patients, thus 260 patients (130 patients per arm), on a week 12/14 week criterion (HCV RNA viral load at W12/W14).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
Hepatitis C - Genotype 4, SVR (Sustained Virological Response), Vitamin D, Treatment Naïve

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vitamin D
Arm Type
Experimental
Arm Description
Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Pegylated Interferon Alpha 2b + Ribavirin
Intervention Type
Drug
Intervention Name(s)
Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin
Other Intervention Name(s)
Vidrop, PegIntron, Rebetol
Intervention Description
Vitamin D ARM: 28000UI/week during 4 weeks (lead in phase) then 28000 UI/week associated with PegIFN/RBV during 48 weeks
Primary Outcome Measure Information:
Title
Proportion of patients with Sustained Virological Response (SVR).
Description
Proportion of patients with Sustained Virological Response (SVR) as defined by HCV RNA below the detection limit based on quantitative PCR 12 weeks after stopping treatment.
Time Frame
60 Weeks after peg-IFN/RBV initiation
Secondary Outcome Measure Information:
Title
Rapid Virological Response (RVR)
Description
HCV RNA at 4 weeks post initiation of combination therapy (PEG IFN + RBV)
Time Frame
4 Weeks after peg-IFN/RBV initiation
Title
Early Virological Response (EVR)
Description
HCV RNA at 12 weeks post initiation of combination therapy
Time Frame
12 Weeks after peg-IFN/RBV initiation
Title
End of Treatment Response (ETR)
Description
HCV RNA at end of treatment (week 48)
Time Frame
48 Weeks after peg-IFN/RBV initiation
Title
Normalization of ALT during treatment and 12 weeks after the end of treatment
Time Frame
From 2 Weeks after peg-IFN/RBV initiation to End of Follow-up (Week 60)
Title
Incidence of serious adverse events (SAE) grade 3 and 4 (ANRS scale)
Description
incidence of SAE leading to dosage reduction or treatment cessation, percentage of patients treated by EPO and G-CSF
Time Frame
From Lead-in phase (Week -4) to End of Follow-up (Week 60)
Title
Evolution of FibroScan values between pre-inclusion and week 60
Time Frame
At Screening Visit 2 (S2) and at End of Follow-up (Week 60)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Common with National Program for Viral Hepatitis Age: 18 years to 60 years Positive HCV antibodies using a third generation test Detectable HCV RNA by PCR Liver biopsy showing chronic hepatitis with either a METAVIR score F1 with elevated liver enzymes or scores F2/F3 Naïve to treatment with PEG-IFN and RBV HBs antigen negative Prothrombin time ≥60 %, normal bilirubin, alpha-foeto protein < 3*normal range of the laboratory, anti-nuclear antibodies<1/160 Effective contraception during the treatment period; no breast-feeding Specific to the trial Prior approval from the Ministry of Health to be treated as part of the National Program with allocation to Peg-IFN α2b treatment Living <100 km from Cairo and able to come to the centre every week for the treatment Signed informed consent and willingness to participate in the trial Naïve to treatment with vitamin D (received vitamin D less than 30 consecutive days in the 3 months preceding inclusion) Biopsy slide validated by NHTMRI pathologist Exclusion Criteria: Common with National program for Viral Hepatitis Serious co-morbid conditions such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes (HbA1C>8%) , chronic obstructive pulmonary disease Major uncontrolled depressive illness Solid transplant organ (renal, heart, or lung) Untreated thyroid disease History of previous anti-HCV therapy Body mass index (BMI) greater than 30 kg/m² Known human immunodeficiency virus (HIV) coinfection: although HIV testing will not be proposed or done, patients with known HIV coinfection will not be included in the trial Anti-HCV therapy contraindications: hypersensitivity to one of the two drugs (PEG-IFN, RBV) pregnancy or unwilling to comply with adequate contraception breast-feeding neutropenia (<1500/mm3) anaemia (<11g/dL for women ; <12g/dL for men) thrombocytopenia (<100,000/mm3) elevated creatinin (>1.5mg/dL) concomitant liver disease other than hepatitis C (immuno-active chronic hepatitis B, autoimmune hepatitis, alcoholic liver disease, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease) liver biopsy showing severe steatosis (>66%) and steatohepatitis; decompensated cirrhosis (Child Pugh>A); hepatocellular carcinoma, METAVIR score F4. TSH>5 mU/L Specific to the trial Patients allocated to Peg-IFN alpha 2a treatment Hypersensitivity to vitamin D Vitamin D contraindications: hypercalcaemia (fasting calcaemia >105 mg/L or 2.62 mmol/L) ratio calciuria / creatininuria (fasting ratio >1 mmol Ca/mmol creatinin) hyperphosphatemia (>1.5 mmol/L) calcium lithiasis patients being treated with thiazide diuretics (risk of hypercalcaemia with vitamin D treatment) patients being treated with glucocorticoïds (decrease in vitamin D efficacy) postmenopausal women treated by vitamin D and calcium for osteoporosis Treatment by vitamin D more than 30 consecutive days in the 3 months preceding inclusion in the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gamal Esmat, MD, PhD
Organizational Affiliation
NHTMRI, Cairo, Egypt
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Arnaud Fontanet, MD, PhD
Organizational Affiliation
Institut Pasteur, Paris France
Official's Role
Study Chair
Facility Information:
Facility Name
NHTMRI
City
Cairo
Country
Egypt

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of the Combination Vitamin D With Standard of Care in Egyptian Patients With Untreated Chronic Hepatitis C

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