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

NCT ID: NCT00136318

Last Updated: 2013-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2008-09-30

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,...)

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Escitalopram

Intervention Type: DRUG

Peginterferon alfa-2a

Intervention Type: DRUG

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.

Ribavirin

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Peginterferon alfa-2a

Intervention Type: DRUG

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.

Ribavirin

Intervention Type: DRUG

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.

Interventions

Escitalopram

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Peginterferon alfa-2a

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.

Intervention Type: DRUG

Ribavirin

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.

Intervention Type: DRUG

Other Intervention Names

PEG-IFN alfa-2a; Pegasys

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

M. Schaefer, MD

Martin Schaefer, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Berg, Prof. Dr.

Role: STUDY_CHAIR

Charité

Martin Schaefer, Prof. Dr.

Role: STUDY_CHAIR

Charite University, Berlin, Germany

Locations

Department of Gastroenterolgy and Rheumatology, Sektion Hepatology

Leipzig, , Germany

Countries

Germany

References

Sarkar S, Sarkar R, Berg T, Schaefer M. Sadness and mild cognitive impairment as predictors for interferon-alpha-induced depression in patients with hepatitis C. Br J Psychiatry. 2015 Jan;206(1):45-51. doi: 10.1192/bjp.bp.113.141770. Epub 2014 Oct 30.

Reference Type: DERIVED

PMID: 25359924 (View on PubMed)

Schaefer M, Sarkar R, Knop V, Effenberger S, Friebe A, Heinze L, Spengler U, Schlaepfer T, Reimer J, Buggisch P, Ockenga J, Link R, Rentrop M, Weidenbach H, Fromm G, Lieb K, Baumert TF, Heinz A, Discher T, Neumann K, Zeuzem S, Berg T. Escitalopram for the prevention of peginterferon-alpha2a-associated depression in hepatitis C virus-infected patients without previous psychiatric disease: a randomized trial. Ann Intern Med. 2012 Jul 17;157(2):94-103. doi: 10.7326/0003-4819-157-2-201207170-00006.

Reference Type: DERIVED

PMID: 22801672 (View on PubMed)

Other Identifiers

ML18075

Identifier Type: -

Identifier Source: org_study_id