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

NCT00136318 | Completed Phase 3 Results DMC

• 1 other identifier: ML18075
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 1

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

Keywords

Pegasys-Induced depression

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

• 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

Study Arms (2)

Escitalopram

ACTIVE COMPARATOR

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; Drug: Peginterferon alfa-2a; Drug: Ribavirin

Placebo

PLACEBO COMPARATOR

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; Drug: Peginterferon alfa-2a; Drug: Ribavirin

Interventions

Escitalopram DRUG

Escitalopram

Placebo DRUG

Placebo

Peginterferon alfa-2a 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.

Also known as: PEG-IFN alfa-2a, Pegasys

Escitalopram; Placebo

Ribavirin 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.

Escitalopram; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic hepatitis C infection defined as positive anti-HCV antibodies and serum HCV-RNA \>1000 IU/ml, naive to antiviral treatment
• age \>18 years

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Department of Gastroenterolgy and Rheumatology, Sektion Hepatology

Leipzig, 04103, Germany

Location

Related Publications (2)

• 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.

  PMID: 25359924 DERIVED

• 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.

  PMID: 22801672 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Escitalopram; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Random assignment of patients before the preobservation period followed by patient withdrawal from the trial independent of antidepressant treatment weakens the strength of the randomization.

Results Point of Contact

• Title: Professor Dr. Martin Schaefer
• Organization: Kliniken Essen-Mitte, Department of Psychiatry

m.schaefer@kliniken-essen-mitte.de

+49201-17430001

Study Officials

• Thomas Berg, Prof. Dr.

  Charité

  STUDY CHAIR

• Martin Schaefer, Prof. Dr.

  Charite University, Berlin, Germany

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Martin Schaefer, MD

Study Record Dates

• First Submitted: August 26, 2005
• First Posted: August 29, 2005
• Study Start: January 1, 2004
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: March 21, 2013
• Results First Posted: March 21, 2013

Record last verified: 2013-03

Locations

DE (1)