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

Depression Clinical Trial

— CIPPAD  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00136318
• Other study ID #: ML18075
• Status: Completed
• Phase: Phase 3
• First received: August 26, 2005
• Last updated: March 20, 2013
• Start date: January 2004
• Est. completion date: September 2008

Study information

• Verified date: March 2013
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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,...)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 208
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Drug:
• Escitalopram

• Placebo

• 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.
• 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.

Locations

Country	Name	City	State
Germany	Department of Gastroenterolgy and Rheumatology, Sektion Hepatology	Leipzig

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Incidence of Major Depression Defined by Diagnostic and Statistical Manual IV (DSM-IV) Criteria		major depression during 24 or 48 weeks of antiviral therapy	No
Secondary	Severe Depression Defined as a MADRS Score of 25 or Higher		severe depression during 24 or 48 weeks of antiviral therapy	No
Secondary	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	No
Secondary	Sustained Virologic Response	(negative Polymerase Chain Reaction (PCR) 6 months after the end of antiviral treatment)	assessed 24 weeks after end of antiviral treatment	No
Secondary	Tolerability		assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment	Yes
Secondary	Safety		assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment	Yes