Trial Outcomes & Findings for Escitalopram for the Prevention of PEGASYS-associated Depression in Hepatitis C Virus-infected Patients (NCT NCT00136318)

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

208 participants

Primary outcome timeframe

50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3

Results posted on

2013-03-21

Participant Flow

A total of 208 of the 300 patients screened were enrolled between August 2004 and September 2008 in different centers in the pre-observation period. Overall 181 patients started the treatment period by taking escitalopram or placebo.

A total of 208 of the 300 patients screened were enrolled between August 2004 and September 2008. 92 patients did not meet the inclusion criteria, had exclusion criteria or did not want to participate in the trial.27 patients stopped the trial during the preobservation period before the trial started by taking antidepressant or placebo therapy.

Participant milestones

Participant milestones
Measure	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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	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. Peginterferon alfa-2a : Placebo : Ribavirin :
Overall Study STARTED	90	91
Overall Study COMPLETED	83	84
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	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. Peginterferon alfa-2a : Placebo : Ribavirin :
Overall Study Adverse Event	5	5
Overall Study Withdrawal by Subject	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Escitalopram n=90 Participants 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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	Placebo n=91 Participants 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. Peginterferon alfa-2a : Placebo : Ribavirin :	Total n=181 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	84 Participants n=5 Participants	84 Participants n=7 Participants	168 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age Continuous	46.2 years STANDARD_DEVIATION 11 • n=5 Participants	48.5 years STANDARD_DEVIATION 11 • n=7 Participants	47.4 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	43 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	48 Participants n=7 Participants	96 Participants n=5 Participants
Region of Enrollment Germany	90 participants n=5 Participants	91 participants n=7 Participants	181 participants n=5 Participants

PRIMARY outcome

Timeframe: 50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Escitalopram n=90 Participants 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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	Placebo n=91 Participants 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. Peginterferon alfa-2a : Placebo : Ribavirin :
Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher	32 percentage of participants Interval 21.0 to 43.0	59 percentage of participants Interval 48.0 to 69.0

SECONDARY outcome

Timeframe: Patients free of depression during 24 or 48 weeks of antiviral therapy

Population: Number of patients per group who did not develop any depressive episode during 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

Outcome measures

Outcome measures
Measure	Escitalopram n=90 Participants 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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	Placebo n=91 Participants 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. Peginterferon alfa-2a : Placebo : Ribavirin :
Proportion of Patients Without Depression (Defined as a MADRS Score of 13 or Higher)	60 participants	40 participants

SECONDARY outcome

Timeframe: major depression during 24 or 48 weeks of antiviral therapy

Population: The final analysis included only patients who received at least 1 dose of escitalopram or placebo. Between-group differences for the secondary outcome parameters were calculated with a chi-square test.

Outcome measures

Outcome measures
Measure	Escitalopram n=90 Participants 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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	Placebo n=91 Participants 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. Peginterferon alfa-2a : Placebo : Ribavirin :
Incidence of Major Depression Defined by Diagnostic and Statistical Manual IV (DSM-IV) Criteria	8 percentage of participants Interval 4.0 to 15.0	17 percentage of participants Interval 12.0 to 28.0

SECONDARY outcome

Timeframe: severe depression during 24 or 48 weeks of antiviral therapy

Population: The final analysis included only patients who received at least 1 dose of escitalopram or placebo. Between-group differences for the secondary outcome parameters were calculated with a chi-square test.

Outcome measures

Outcome measures
Measure	Escitalopram n=90 Participants 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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	Placebo n=91 Participants 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. Peginterferon alfa-2a : Placebo : Ribavirin :
Severe Depression Defined as a MADRS Score of 25 or Higher	1 percentage of participants Interval 0.3 to 6.0	12 percentage of participants Interval 7.0 to 21.0

SECONDARY outcome

Timeframe: assessed 2,4,12,24 and 48 weeks of antiviral treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: assessed 24 weeks after end of antiviral treatment

Population: The final analysis included only patients who received at least 1 dose of escitalopram or placebo. Between-group differences for the secondary outcome parameters were calculated with a chi-square test.

(negative Polymerase Chain Reaction (PCR) 6 months after the end of antiviral treatment)

Outcome measures

Outcome measures
Measure	Escitalopram n=90 Participants 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. Peginterferon alfa-2a : Escitalopram : Ribavirin :	Placebo n=91 Participants 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. Peginterferon alfa-2a : Placebo : Ribavirin :
Sustained Virologic Response	56 percentage of participants Interval 46.0 to 66.0	46 percentage of participants Interval 37.0 to 57.0

SECONDARY outcome

Timeframe: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment

Outcome measures

Outcome data not reported

Adverse Events

Escitalopram

Serious events: 5 serious events

Other events: 67 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Escitalopram n=90 participants at risk	Placebo n=91 participants at risk
Psychiatric disorders drug abuse	1.1% 1/90	0.00% 0/91
Psychiatric disorders self-harming behavior	1.1% 1/90	0.00% 0/91
Neoplasms benign, malignant and unspecified (incl cysts and polyps) renal failure	1.1% 1/90	0.00% 0/91
Neoplasms benign, malignant and unspecified (incl cysts and polyps) cerebral tumor	1.1% 1/90	0.00% 0/91
General disorders jaundice	1.1% 1/90	0.00% 0/91
Eye disorders retinopathy	0.00% 0/90	1.1% 1/91
Neoplasms benign, malignant and unspecified (incl cysts and polyps) glioblastoma	0.00% 0/90	1.1% 1/91
Psychiatric disorders severe depression	0.00% 0/90	3.3% 3/91

Other adverse events

Other adverse events
Measure	Escitalopram n=90 participants at risk	Placebo n=91 participants at risk
General disorders Fatigue	48.9% 44/90	60.4% 55/91
General disorders Dizziness	14.4% 13/90	25.3% 23/91
General disorders Anemia	17.8% 16/90	22.0% 20/91

Additional Information

Professor Dr. Martin Schaefer

Kliniken Essen-Mitte, Department of Psychiatry

Phone: +49201-17430001

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place