Peginterferon Alpha-2a Maintenance Therapy for Portal Hypertension in Patients With Hepatitis C
|First Received Date ICMJE||November 9, 2005|
|Last Updated Date||December 14, 2007|
|Start Date ICMJE||November 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Changes in portal pressure after 6 moths of treatment with peginterferon alfa-2a will be calculated by comparing portal pressure at the end of HALT-C to values obtained after 6 months of peginterferon.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00252642 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Peginterferon Alpha-2a Maintenance Therapy for Portal Hypertension in Patients With Hepatitis C|
|Official Title ICMJE||The Impact of Peginterferon Alpha-2a Maintenance Therapy on Portal Hypertension in Patients With Chronic Hepatitis C Virus Infection and Advanced Fibrosis and Cirrhosis Enrolled in the HALT-C Trial|
The primary purpose of this study is to determine if peginterferon alpha-2a maintenance therapy (90 mcg/week) will lower portal pressure in patients with hepatitis C virus infections and advanced fibrosis or cirrhosis.
Portal hypertension develops in patients with advanced fibrosis and cirrhosis and is the primary driving force leading to complications of cirrhosis, hepatic decompensation and mortality in patients with chronic liver disease. None of the three major complications of advanced liver disease variceal hemorrhage, ascites and hepatic encephalopathy occur in the absence of portal hypertension. As a result, measuring portal pressure and treating portal hypertension is an important part in the management of patients with advanced liver disease. A sub-study to measure portal pressure was initially proposed as part of the HALT-C clinical trial. Unfortunately, only 2/10 centers elected to participate in this sub-study and as a result, this was eventually dropped as a sub-study within the HALT-C trial.
Recent data has suggested that interferon therapy may selectively reduce portal hypertension in patients with cirrhosis. In an abstract presented at the 2004 annual meeting of the European Association for the Study of the Liver (EASL), portal pressure declined significantly in patients with NR after 6 months of treatment with peginterferon and ribavirin. At the time portal pressure was measured in this study, a transjugular liver biopsy was also performed to assess the effects of treatment on hepatic histology. Despite a reduction in portal pressure, no reduction in hepatic fibrosis score was observed. This suggested that interferon may reduce portal pressure through a direct affect on the hepatic vasculature; and suggests that interferon may prevent complications of cirrhosis regardless of its effects on HCV RNA and hepatic inflammation. Since portal pressure is the primary factor responsible for complications of cirrhosis including variceal hemorrhage, ascites and hepatic encephalopathy, these preliminary results suggest that maintenance interferon therapy could possibly prevent these complications.
Preliminary results form a randomized, controlled trial of maintenance interferon therapy (Co-Pilot) presented at the 2004 annual meeting of the American Association of the study of Liver Disease (AASLD) did in fact demonstrate that patients with advanced fibrosis or cirrhosis who received maintenance peginterferon maintenance therapy over a two year period had a significant reduction in the incidence of variceal hemorrhage compared to that observed in the control group. The HALT-C trial provides an ideal patient population in which to further assess the effects of maintenance interferon therapy on portal hypertension.
The first patients who were enrolled into the HALT-C trial are scheduled to complete four years of maintenance therapy near the end of 2004. This provides an optimal time point at which to assess the impact of maintenance interferon therapy on portal pressure. Although an ideal study design would have been to measure portal pressure at baseline and then again after 4 years in both the control and treatment groups, measuring portal pressure at the completion of the study will still provide significant information regarding the impact of maintenance interferon therapy on portal hypertension. The number of patients enrolled into HALT-C at these two sites is substantial (nearly 400 patients) and since the control and maintenance therapy groups were well matched at the start of the study we can assume that baseline portal pressure at the time of randomization was not significantly different in the two groups. Thus, if 4 years of maintenance interferon therapy does indeed reduce portal pressure a significant difference in mean portal pressure should be observed between the two groups at the completion of the HALT-C trial.
Patients who were randomized to the control arm of HALT-C during the past four years have received no treatment for chronic HCV during the past 4 years. Such patients will be offered the opportunity to receive peginterferon maintenance therapy for 6 months as part of this protocol and then undergo repeat measurement of portal pressure to determine if they could potentially benefit from remaining on peginterferon maintenance therapy long term
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Peginterferon Alpha-2a|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||September 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00252642|
|Other Study ID Numbers ICMJE||PH-VCU-05|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Mitchell L. Shiffman, MD, Virginia Commonwealth Unversity|
|Study Sponsor ICMJE||Virginia Commonwealth University|
|Collaborators ICMJE||Hoffmann-La Roche|
|Information Provided By||Virginia Commonwealth University|
|Verification Date||August 2006|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP