Escitalopram for the Prevention of PEGASYS-associated Depression in Hepatitis C Virus-infected Patients

Study Overview
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Brief Summary
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Primary end points incidence of depression defined as a Montgomery Asberg Depression Scale Score (MADRS) of 13 or higher during antiviral therapy (up to 48 weeks, depending on genotype) effect of an antidepressive pre-treatment over two weeks and a continuously concomitant treatment with Escitalopram (S-citalopram) on frequency and severity of depression in patients with chronic hepatitis C (HCV) treated with Peg-interferon alfa-2a (PEGASYS) and ribavirin, measured by the Montgomery Asberg Depression Scale Secondary end points time to depression defined as a MADRS score of 13 or higher incidence of major depression defined by Diagnostic and Statistical Manual IV (DSM-IV) criteria severe depression according to MADRS scale (score 25 or higher) Health related quality of life (HRQOL) measured by the Short Form 36 (SF-36) sustained virologic response tolerability safety changes/group differences in other psychiatric depression scales (Hamilton Depression Rating Scale, Beck Depression Inventory) Other investigations: cognitive function, anxiety (word fluency test, trail making test part A and B, othe scales) Predictive parameters for patients especially gaining from an antidepressive therapy (e.g. age, gender, weight, height, alanine aminotransferase (ALAT) quotient defined as median ALAT values before treatment divided by the upper standard value, HCV-RNA serum concentration level of fibrosis in liver histology, baseline values of the different psychometric scales) alanine aminotransferase (ALAT), aspartate transaminase (ASAT), thyrotrophin (TSH) biomarkers (genetic parameters, cytokines,...)

Official Title
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Efficacy and Tolerability of Escitalopram for the Prevention of Pegylated Interferon Alfa Associated Depression in Patients With Chronic Hepatitis C Infection: a Randomized Controlled Trial.

Conditions
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Depression

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Placebo
* Drug: Peginterferon alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis C infection defined as positive anti-HCV antibodies and serum HCV-RNA >1000 IU/ml, naive to antiviral treatment age >18 years Exclusion Criteria: Antidepressive treatment within the last 3 years Psychiatric diseases including major depressive disorders in past medical history Active substance abuse during the last 12 months Pregnancy, lactation, wish to become pregnant Hepatitis B (HBV)/HIV-coinfection Decompensated liver disease, hepatocellular carcinoma, history of bleeding esophageal varices Neutropenia (<1500/ul), thrombocytopenia (<70/nl), anemia (<12g/dl in females, <13g/dl in males) History of autoimmune disease History of organ transplantation, concomitant liver disease, severe cardiopulmonary disease, hemolytic anemia, malignant disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Escitalopram<br>After the preobservation period,patients received escitalopram, 10 mg per day. During treatment period, all patients began receiving antiviral therapy with PEG-interferon plus ribavirin with continuous concomitant administration of escitalopram. | Drug: Escitalopram<br> <br> Drug: Peginterferon alfa-2a<br>* Patients with HCV genotype 1 or 4 received treatment for 48 weeks with PEGinterferon-alfa2a, 180 mcg weekly. Patients with genotype 2 or 3 received PEGinterferon-alfa2a, 180 mcg weekly.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Patients with HCV genotype 1 or 4 received treatment for 48 weeks with ribavirin, 1000 mg per day (body weight 75 kg) or 1200 mg per day (body weight, 75 kg). Patients with HCV genotype 2 or 3 received ribavirin, 800 mg per day for 24 weeks.<br>|
| Placebo Comparator: Placebo<br>After the preobservation period, patients received placebo. After 2 weeks of antidepressant pretreatment, all patients began receiving antiviral therapy with PEG-interferon plus ribavirin with continuous concomitant administration of placebo. | Drug: Placebo<br> <br> Drug: Peginterferon alfa-2a<br>* Patients with HCV genotype 1 or 4 received treatment for 48 weeks with PEGinterferon-alfa2a, 180 mcg weekly. Patients with genotype 2 or 3 received PEGinterferon-alfa2a, 180 mcg weekly.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Patients with HCV genotype 1 or 4 received treatment for 48 weeks with ribavirin, 1000 mg per day (body weight 75 kg) or 1200 mg per day (body weight, 75 kg). Patients with HCV genotype 2 or 3 received ribavirin, 800 mg per day for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher | Clinically relevant depression (MADRS score of 13 or higher) during antiviral treatment presented as percentage of participants with MADRS scores > 13 (entire time period: from starting study medication until end of antiviral treatment = 48 weeks in patients with genotype 1 or 4 and 24 weeks for patients with genotype 2 or 3) | 50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Without Depression (Defined as a MADRS Score of 13 or Higher) | Number of patients who did not develop at any time of antiviral treatment (up to 48 weeks) a MADRS score of 13 or more as a sign of clinically relevant depression | Patients free of depression during 24 or 48 weeks of antiviral therapy | 
| Incidence of Major Depression Defined by Diagnostic and Statistical Manual IV (DSM-IV) Criteria |  | major depression during 24 or 48 weeks of antiviral therapy | 
| Severe Depression Defined as a MADRS Score of 25 or Higher |  | severe depression during 24 or 48 weeks of antiviral therapy | 
| Health Related Quality of Life (HRQOL) Measured by the Short Form 36 (SF-36) |  | assessed 2,4,12,24 and 48 weeks of antiviral treatment | 
| Sustained Virologic Response | (negative Polymerase Chain Reaction (PCR) 6 months after the end of antiviral treatment) | assessed 24 weeks after end of antiviral treatment | 
| Tolerability |  | assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment | 
| Safety |  | assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pegasys-Induced depression