Ignite Creation Date:
2024-05-05 @ 6:33 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00502970
Status:
COMPLETED
Last Update Posted:
2008-01-11
First Post:
2007-07-16
Brief Title:
Short Course of Interferon Treatment in Patients With HCV Infection
Sponsor:
Aga Khan University
Organization:
Aga Khan University
Study Overview
Official Title:
A Randomized Trial Comparing a Short Course Versus Standard Treatment in Patients With Chronic Hepatitis C Virus Infection
Status:
COMPLETED
Status Verified Date:
2008-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
STAR
Brief Summary:
To determine if a shorter course of interferon and ribavirin therapy will be sufficient in carefully selected patients with chronic hepatitis C virus genotype 3 infection as compared to the standard length of treatment of 6 months
Detailed Description:
1 INTRODUCTION
11 Hepatitis C Hepatitis C Virus HCV is a major cause of chronic hepatitis and hepatic fibrosis1 Acute infection advances to chronicity in up to 80 of patients which can further progress to cirrhosis and hepatocellular carcinoma in a significant number1
Hepatitis C is a global problem prevalent in industrialized as well as in the developing world2 It is a major cause of chronic liver disease CLD in Pakistan and has surpassed hepatitis B as the single most important cause for cirrhosis and hepatocellular carcinoma HCC in Pakistan 3
12 Study Medications A combination of interferon and ribavirin therapy has been the standard of care world-wide for the past few years1 2 Standard treatment duration is for 24 weeks for genotype non 1 and 48 weeks for genotype 12
121 Interferon Alfa 2a Interferon Alfa was the first drug shown to have bioactivity against HCV Combining ribavirin with interferon Alfa was found to be more effective than interferon Alfa mono-therapy in previously untreated patients as well in patients who relapsed after one or more courses of interferon Alfa therapy2
122 Ribavirin Ribavirin is a guanosine analogue that inhibits the in vitro replication of a wide range of RNA and DNA viruses1 The mechanism of antiviral activity is not fully defined although it may involve alteration of cellular nucleotide pools and inhibition of viral RNA synthesis1 4 Ribavirin monotherapy has little or no effect on the replication of HCV but can result in normalization of serum ALT activity and improvement in liver histology However relapse occurs in nearly all patients treated with ribavirin alone1
Combining Ribavirin with Interferon has been found to be more effective than Interferon monotherapy in the treatment of chronic hepatitis C In a large clinical trial of 1121 patients a sustained virological response SVR was achieved in 53 of patients treated with Interferon plus Ribavirin as compared to 29 of patients treated with Interferon alone1 4
2 RATIONALE Most treatment related studies on HCV have come from the West where the most prevalent genotype is 1 their results however do not necessarily reflect the outcome in a developing country like Pakistan where studies have already confirmed that the most prevalent genotype is 32 Success rates have globally been reported to be high when treating genotype 3 it has long been observed that patients infected with genotype 2 and 3 respond better to interferon therapy than patients infected with genotype 11 3
Favorable prognostic factors have been identified which predict a better response to therapy in the treatment of chronic HCV These include
Younger age
Genotype 3
No cirrhosis on liver biopsy and
Absence of alcohol or drug abuse1 7
Few studies have investigated the efficacy of a short course therapy for patients with favorable predictive factors most of these studies have used interferon monotherapy4 5 while others have used a combination treatment for shorter duration in relapsed patients6 There is evidence that combination treatment may be beneficial when used as induction therapy followed by interferon in a short course program 7 Cases infected with HCV genotype 3 being treated for as little as 4-12 weeks and remaining sustained responders have been reported8
Since HCV genotype 3 responds so well to a combination of interferon and Ribavarin it has been suggested that this patient population may have a similar response to a shorter duration of therapy7 8 9 The efficacy of a short course interferon and Ribavarin combination therapy compared to a longer course of therapy has not been compared in the treatment of patients with favorable predictive factors
21 Rationale for Dosage Selection
1221 Interferon Alfa 2a The dose chosen for interferon Alfa 2a 3 million units thrice weekly sc is the dose currently approved in Pakistan for combination therapy with ribavarin1
1222 Ribavarin The dose chosen for Ribavarin 800-1200 mg per day is the dose currently approved in Pakistan for combination therapy with interferon in patients with HCV1
3 HYPOTHESIS In patients with chronic hepatitis C infection with favorable predictive factors for treatment a short course of combination therapy with interferon and Ribavarin is equally efficacious as the longer course of treatment
4 OBJECTIVE To determine whether 16 weeks of interferon and Ribavarin therapy is as effective as 24 weeks of therapy in achieving sustained virological response in patients with favorable predictive factors who are infected with HCV genotype 3
5 SIGNIFICANCE Pakistan has an enormous burden of chronic HCV infection The cost of treatment is prohibitive and is unaffordable for a large proportion of our population2 3 A short course therapy comparable to the standard regimen would have significant implications a striking decrease in financial burden on the health care system of the country as well as the patients and a reduction in patient exposure to both medications resulting in decreased treatment related adverse effects In addition a larger number of patients will be able to afford the treatment due to a decrease in treatment duration and in turn the overall cost
11 Hepatitis C Hepatitis C Virus HCV is a major cause of chronic hepatitis and hepatic fibrosis1 Acute infection advances to chronicity in up to 80 of patients which can further progress to cirrhosis and hepatocellular carcinoma in a significant number1
Hepatitis C is a global problem prevalent in industrialized as well as in the developing world2 It is a major cause of chronic liver disease CLD in Pakistan and has surpassed hepatitis B as the single most important cause for cirrhosis and hepatocellular carcinoma HCC in Pakistan 3
12 Study Medications A combination of interferon and ribavirin therapy has been the standard of care world-wide for the past few years1 2 Standard treatment duration is for 24 weeks for genotype non 1 and 48 weeks for genotype 12
121 Interferon Alfa 2a Interferon Alfa was the first drug shown to have bioactivity against HCV Combining ribavirin with interferon Alfa was found to be more effective than interferon Alfa mono-therapy in previously untreated patients as well in patients who relapsed after one or more courses of interferon Alfa therapy2
122 Ribavirin Ribavirin is a guanosine analogue that inhibits the in vitro replication of a wide range of RNA and DNA viruses1 The mechanism of antiviral activity is not fully defined although it may involve alteration of cellular nucleotide pools and inhibition of viral RNA synthesis1 4 Ribavirin monotherapy has little or no effect on the replication of HCV but can result in normalization of serum ALT activity and improvement in liver histology However relapse occurs in nearly all patients treated with ribavirin alone1
Combining Ribavirin with Interferon has been found to be more effective than Interferon monotherapy in the treatment of chronic hepatitis C In a large clinical trial of 1121 patients a sustained virological response SVR was achieved in 53 of patients treated with Interferon plus Ribavirin as compared to 29 of patients treated with Interferon alone1 4
2 RATIONALE Most treatment related studies on HCV have come from the West where the most prevalent genotype is 1 their results however do not necessarily reflect the outcome in a developing country like Pakistan where studies have already confirmed that the most prevalent genotype is 32 Success rates have globally been reported to be high when treating genotype 3 it has long been observed that patients infected with genotype 2 and 3 respond better to interferon therapy than patients infected with genotype 11 3
Favorable prognostic factors have been identified which predict a better response to therapy in the treatment of chronic HCV These include
Younger age
Genotype 3
No cirrhosis on liver biopsy and
Absence of alcohol or drug abuse1 7
Few studies have investigated the efficacy of a short course therapy for patients with favorable predictive factors most of these studies have used interferon monotherapy4 5 while others have used a combination treatment for shorter duration in relapsed patients6 There is evidence that combination treatment may be beneficial when used as induction therapy followed by interferon in a short course program 7 Cases infected with HCV genotype 3 being treated for as little as 4-12 weeks and remaining sustained responders have been reported8
Since HCV genotype 3 responds so well to a combination of interferon and Ribavarin it has been suggested that this patient population may have a similar response to a shorter duration of therapy7 8 9 The efficacy of a short course interferon and Ribavarin combination therapy compared to a longer course of therapy has not been compared in the treatment of patients with favorable predictive factors
21 Rationale for Dosage Selection
1221 Interferon Alfa 2a The dose chosen for interferon Alfa 2a 3 million units thrice weekly sc is the dose currently approved in Pakistan for combination therapy with ribavarin1
1222 Ribavarin The dose chosen for Ribavarin 800-1200 mg per day is the dose currently approved in Pakistan for combination therapy with interferon in patients with HCV1
3 HYPOTHESIS In patients with chronic hepatitis C infection with favorable predictive factors for treatment a short course of combination therapy with interferon and Ribavarin is equally efficacious as the longer course of treatment
4 OBJECTIVE To determine whether 16 weeks of interferon and Ribavarin therapy is as effective as 24 weeks of therapy in achieving sustained virological response in patients with favorable predictive factors who are infected with HCV genotype 3
5 SIGNIFICANCE Pakistan has an enormous burden of chronic HCV infection The cost of treatment is prohibitive and is unaffordable for a large proportion of our population2 3 A short course therapy comparable to the standard regimen would have significant implications a striking decrease in financial burden on the health care system of the country as well as the patients and a reduction in patient exposure to both medications resulting in decreased treatment related adverse effects In addition a larger number of patients will be able to afford the treatment due to a decrease in treatment duration and in turn the overall cost
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None