To assess both the beneficial and harmful effects of amantadine for patients with chronic hepatitis C.
Searches
The following electronic databases will be searched: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). The search will be done from inception to 2012 without language restriction. Abstracts from the following congresses will also be searched from 2000 to 2012: AASLD, EASL, and DDW. The references of relevant literatures will be screened. We will also check the clinical trial registry (www.clinicaltrials.gov) for additional studies. Furthermore, we will try to contact specialists and manufactures in the field for unpublished data from randomized trials.
Types of study to be included
Study design of RCT;
Comparison of an antiviral regimen including amantadine to the same antiviral regimen without amantadine;
Use of end-of-treatment virological response (ETR) or sustained virological response (SVR) as clinical endpoints.
Condition or domain being studied
Hepatitis C is an infectious disease of the liver caused by the hepatitis C virus (HCV). HCV is a major public health problem and a leading cause of chronic liver disease. About 50-80% of patients with primary HCV infection develop chronic hepatitis C (CHC), and have a high possibility to develop cirrhosis and hepatocellular carcinoma. Current therapy for CHC is interferon plus libavirin with or without protease inhibitor according to HCV genotypes. Amantadine is an antiviral agent. Several RCTs have been conducted to evaluate its therapeutic effect on CHC alone or with other drugs. However, their results are controversial. Deltenre et al (2004) performed a meta-analysis, and found that combination therapy with amantadine is of no effect upon naïve patients or relapsers and triple therapy with amantadine improves the sustained virological response in non-responders. But new RCTs are required to confirm their meta-analysis. In the past eight years, several RCTs have been published.
Therefore, there is a need to update the meta-analysis. Deltenre et al did not evaluate side effects of amantadine. In the updated meta-analysis, we will also include this.
Participants/ population
People with chronic hepatitis C.
Intervention(s), exposure(s)
Amantadine alone, in combination with interferon, interferon plus ribavirin, or other interventions.
Comparator(s)/ control
The same antiviral regimen without amantadine.
Outcome(s)
Primary outcomes
Sustained virological response (SVR).
SVR is defined as undetectable HCV RNA at least six months after treatment cessation. Treatment duration can be dependent upon genotype and is 24 weeks or 48 weeks.
Secondary outcomes
End-of-treatment virological response (ETR);
Biological response (e.g. ALT);
Histology response;
Mortality;
Adverse effects;
Discontinuation because of adverse events.
Data extraction, (selection and coding)
Two reviewers will independently extract data using a standardized data extraction form including the following information: characteristics of the study (study settings, designs, etc), characteristics of participants and disease (number of participants, age, sex, genotype of HCV, etc.), intervention (the name of the antiviral agents, dosage, duration, etc.), and outcomes (SVR, ETR, biological response, histology response, mortality, adverse effects, etc.).
Risk of bias (quality) assessment
We will address methodological quality including adequacy of random sequence generation, allocation concealment, blinding, loss of follow-up, selective reporting or other biases. Judgment regarding the presence of methodological biases will be made according to the Cochrane criteria guidelines.
Strategy for data synthesis
We will do analysis according to the Cochrane Handbook of Systematic Review. Dichotomous data will be presented as relative risk (RR) with 95% confidence intervals (CIs). Heterogeneity will be checked by a chi-square based Q test. A P value of more than 0.05 for the Q test indicates a lack of heterogeneity among the studies, so the summary RR estimate of each study will be calculated by the Mantel-Haenszel method. Otherwise, the DerSimonian and Laird method will be used. Egger’s and Begg’s graphical methods will be used to provide diagnosis of the potential publication bias.
Analysis of subgroups or subsets
Where data allow, subgroup analysis will be done according to intervention, genotypes of HCV, study quality, and other characteristics of included studies.
Contact details for further information
Wenjun Wang
157 Xiwu Road, Xian 710004, Shaanxi Province, China
alargo@163.com
Organisational affiliation of the review
Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University
Review team
Dr Wenjun Wang, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University Dr Shuangsuo Dang, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University Dr Yaping Li, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University Dr Mei Li, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University Dr Xiaoli Jia, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University Dr Song Zhai, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University Dr Mingzhu Sun, Department of Infectious Diseases, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University
Anticipated or actual start date
17 September 2012
Anticipated completion date
17 March 2013
Funding sources/sponsors
None
Conflicts of interest
None known
Language
English
Country
China
Subject index terms status
Subject indexing assigned by CRD
Subject index terms
Amantadine; Hepatitis C, Chronic; Humans;
Date of registration in PROSPERO
14 September 2012
Date of publication of this revision
14 September 2012
Stage of review at time of this submission
Started
Completed
Preliminary searches
Yes
Piloting of the study selection process
Formal screening of search results against eligibility criteria
Data extraction
Risk of bias (quality) assessment
Data analysis
Prospective meta-analysis
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.
