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

Phase 3

Completed

Conditions: Depression

Interventions: Drug: Placebo
Drug: Escitalopram
Drug: Peginterferon alfa-2a
Drug: Ribavirin

Registration Number: NCT00136318

Lead Sponsor: Charite University, Berlin, Germany

Brief Summary: 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,...)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 208

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Escitalopram	Escitalopram	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.
Escitalopram	Peginterferon alfa-2a	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.
Escitalopram	Ribavirin	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.
Placebo	Peginterferon alfa-2a	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.
Placebo	Ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher	50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3	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)

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients Without Depression (Defined as a MADRS Score of 13 or Higher)	Patients free of depression during 24 or 48 weeks of antiviral therapy	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
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	assessed 24 weeks after end of antiviral treatment	(negative Polymerase Chain Reaction (PCR) 6 months after the 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