DepressionPhase 3CIPPADNCT00136318

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

A Phase 3 study testing Escitalopram, Peginterferon alfa-2a and Ribavirin in people with Depression, run by Charite University, Berlin, Germany at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Depression
What is being tested?: Escitalopram, Peginterferon alfa-2a and Ribavirin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 208 participants
Where: 1 siteGermany
Study dates: Jan 2004to Sep 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Department of Gastroenterolgy and Rheumatology, Sektion Hepatology
Leipzig, 04103

Other trials in Germany

About this study

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.

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
Being tested: Escitalopram, Placebo, Peginterferon alfa-2a, Ribavirin
Keywords: Pegasys-Induced depression
Medical subject headings: Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EscitalopramDrug
PlaceboDrug
Peginterferon alfa-2aDrug
Also called PEG-IFN alfa-2a, Pegasys
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.
RibavirinDrug
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.

Study groups in NCT00136318
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Placebo; Drug: Peginterferon alfa-2a; Drug: Ribavirin

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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)
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
Measured: 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
Measured: major depression during 24 or 48 weeks of antiviral therapy
Severe Depression Defined as a MADRS Score of 25 or Higher
Measured: severe depression during 24 or 48 weeks of antiviral therapy
Health Related Quality of Life (HRQOL) Measured by the Short Form 36 (SF-36)
Measured: 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)
Measured: assessed 24 weeks after end of antiviral treatment
Tolerability
Measured: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment
Safety
Measured: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2004Sep 2008

First posted29 Aug 2005 (estimated)
Study startJan 2004
Primary completionSep 2008
Study completionSep 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for DepressionStudies of the same condition, open and under way.
More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 208 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00136318
Sponsor's protocol ID: ML18075
Acronym: CIPPAD
Status last verified: Mar 2013
First submitted: 26 Aug 2005
Last updated: 21 Mar 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 25359924
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.
PubMed 22801672

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT00136318
Acronym / sponsor ID: CIPPAD / ML18075
Conditions: Depression
Keywords: Pegasys-Induced depression
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 208 participants (actual)
Lead sponsor: Charite University, Berlin, GermanyUniversity, hospital or other
Study start: Jan 2004
Primary completion: Sep 2008 (actual)
Study completion: Sep 2008 (actual)
First posted: 29 Aug 2005 (estimated)
Results: Posted 21 Mar 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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,...)

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Escitalopram	Active comparator	Drug: Escitalopram, Drug: Peginterferon alfa-2a, Drug: RibavirinAfter 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	Placebo comparator	Drug: Placebo, Drug: Peginterferon alfa-2a, Drug: RibavirinAfter 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Escitalopram	Drug	Escitalopram
Placebo	Drug	Placebo
Peginterferon alfa-2aAlso: PEG-IFN alfa-2a, PegasysPatients 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.	Drug	Escitalopram, Placebo
RibavirinPatients 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.	Drug	Escitalopram, Placebo

Primary outcome

Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher
Time frame: 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)

7 secondary outcomes

Proportion of Patients Without Depression (Defined as a MADRS Score of 13 or Higher)
Time frame: 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
Time frame: major depression during 24 or 48 weeks of antiviral therapy
Severe Depression Defined as a MADRS Score of 25 or Higher
Time frame: severe depression during 24 or 48 weeks of antiviral therapy
Health Related Quality of Life (HRQOL) Measured by the Short Form 36 (SF-36)
Time frame: assessed 2,4,12,24 and 48 weeks of antiviral treatment
Sustained Virologic Response
Time frame: assessed 24 weeks after end of antiviral treatment
Tolerability
Time frame: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment
Safety
Time frame: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment

Results and safety

Results posted to the registry on 21 Mar 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Escitalopram	90	83
Placebo	91	84

Primary outcome: Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher

Time frame: 50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Escitalopram n = 90	Placebo n = 91
Value	32 (21 to 43)	59 (48 to 69)

Population analysed: The final analysis included only patients who received at least one of escitalopram or placebo. Between group differences for the primary outcome parameters were calculated with a chi-square test. For the primary end point (MADRS score of 13 or higher), we treated missing MADRS assessments by multiple imputation.

7 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Escitalopram	5 of 90 (5.6%)	67 of 90 (74.4%)	Not reported
Placebo	5 of 91 (5.5%)	78 of 91 (85.7%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25359924Sarkar 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.
Derived from this study: PubMed 22801672Schaefer 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Thomas Berg, Prof. Dr. study chair

Charité

Martin Schaefer, Prof. Dr. study chair

Charite University, Berlin, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Escitalopram, Peginterferon alfa-2a and Ribavirin in people with Depression, run by Charite University, Berlin, Germany at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher (time frame: 50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00136318, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2013.