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| ID | Type | Description | Link |
|---|---|---|---|
| EudraCT number: 2004-002982-19 |
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| Name | Class |
|---|---|
| Hoffmann-La Roche | INDUSTRY |
| H. Lundbeck A/S | INDUSTRY |
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The purpose of this study is to determine whether the use of an antidepressant (escitalopram) can prevent depressive episodes that appear during the treatment with peg-interferon and ribavirin in patients with chronic hepatitis C.
Chronic hepatitis C is a prevalent condition, and the main cause of chronic liver diseases, including cirrhosis and cancer. Nowadays, interferon-alfa in combination with ribavirin is the main treatment option for this condition. In the last years, interferon molecule has been modified in order to improve tolerance into pegylated interferon.
Interferon-alfa has been associated with a high prevalence of psychiatric side effects, especially major depression (up to 25% of the cases), which is one of the main concerns about using this treatment. In fact, major depression is one of the main reasons of treatment withdrawal and treatment failure.
Major depression induced by interferon-alfa can be successfully treated with antidepressants, but we don't know if antidepressants can also prevent the development of major depression, and if this can be a safe intervention. In the literature, there is only one controlled trial about this issue, in cancer patients, and some open studies in hepatitis C.
In order to evaluate the efficacy, and safety, of an antidepressant (escitalopram) for preventing peginterferon's induced depressive episodes in patients with chronic hepatitis C, we have designed this 14-weeks placebo-controlled, double-blind, randomized clinical trial. Study interventions will be started two weeks before peginterferon + ribavirin's treatment onset.
Subjects included in the study will be patients with chronic hepatitis C who are going to be treated with peginterferon-alfa2a + ribavirin, and without mental disorders requiring active psychotropic treatment.
The main variables studied will be the appearance of a major depressive episode, following Diagnostic & Statistical Manual of Mental Disorders (DSM-IV) criteria, and the total score on the Montgomery-Asberg Depression Rating Scale, along three assessment points at 4, 8 and 12 weeks of treatment with interferon. There will also be a follow-up period of up to 6 months after treatment with interferon is completed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Escitalopram | Experimental | Escitalopram, 15 mg/day |
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| Placebo pill | Placebo Comparator | Placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escitalopram | Drug | 15 mg/day starting 2 weeks before and 12 weeks during interferon therapy |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Developed a Major Depressive Episode According to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Criteria During the First 12 Weeks of Antiviral Treatment. | At least five of the symptoms have been present during the same 1-week period: depressed mood, loss of interest or pleasure, weight or appetite changes, insomnia, agitation or retardation, fatigue, feelings of worthlessness or guilt, diminished ability to think or concentrate, recurrent thoughts of death. At least one of the symptoms is either depressed mood or loss of interest. Diagnoses were made by a trained psychiatrist who applied the mood disorders module from the Structured Clinical Interview for DSM-IV Axis I Disorders, non-patient edition (SCID-I/NP) at each study evaluation. | First three months of interferon treatment. |
| Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid). | Number of participants with negativization of serum hepatitis C Virus Ribonucleic Acid (HCV RNA) 6 months after concluding antiviral therapy (sustained viral response). Negativization was defined as the absence of detectable levels of serum HCV RNA using a polymerase chain reaction. | Six months after the end of interferon treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Total Score in the Montgomery-Asberg Depression Rating Scale | The MADRS is a 10-item scale, clinician-administered, which is sensitive to symptom change during antidepressant treatment. It has been frequently used to measure depressive symptoms during interferon-alpha therapy and exhibits improved internal consistency in patients with co-morbid medical conditions compared with other clinician-administered questionnaires. Items are rated on a scale of 0-6. Scores range from 0 to 60, higher scores meaning higher levels of depression. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Crisanto Diez-Quevedo, MD | Germans Trias i Pujol Hospital | Principal Investigator |
| Ramon Planas, MD | Germans Trias i Pujol Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fundacion Hospital Alcorcon | Alcorcón | Spain | ||||
| Hospital Nuestra Señora de Sonsoles |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21034680 | Result | Diez-Quevedo C, Masnou H, Planas R, Castellvi P, Gimenez D, Morillas RM, Martin-Santos R, Navines R, Sola R, Giner P, Ardevol M, Costa J, Diago M, Pretel J. Prophylactic treatment with escitalopram of pegylated interferon alfa-2a-induced depression in hepatitis C: a 12-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Apr;72(4):522-8. doi: 10.4088/JCP.09m05282blu. Epub 2010 Oct 5. |
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Participants were recruited among chronic hepatitis C patients between 18 and 65 years old, referred by general practitioners between March 2005 and July 2006 to gastroenterology outpatient units in 15 academic general hospitals in Spain, who were suitable to initiate treatment with pegylated interferonalfa-2a and ribavirin.
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| ID | Title | Description |
|---|---|---|
| FG000 | Escitalopram | Patients treated with 15 mg/day of Escitalopram since 2 weeks before starting pegylated interferon and ribavirin until week 12 of antiviral treatment |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy. |
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| 12 weeks after interferon treatment onset |
| Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale. | The Hospital Anxiety and Depression Scale (HADS) is 14-item scale, patient-administered, that allows two independent scores of depression and anxiety. It has been specially designed to apply in patients with comorbid medical conditions as it excludes somatic or vegetative symptoms from the depression subscale. We present data of de depression subscale. The seven-item Depression subscale yields a score of 0-21, with higher scores meaning higher levels of depressive symptoms. | 12 weeks after interferon treatment onset |
| Ávila |
| Spain |
| Hospital Universitari Germans Trias i Pujol | Badalona | 08916 | Spain |
| Hospital del Mar | Barcelona | Spain |
| Hospital Puerta de Hierro | Madrid | Spain |
| Hospital Ramon y Cajal | Madrid | Spain |
| Hospital Universitario La Paz | Madrid | Spain |
| Hospital Universitario La Princesa | Madrid | Spain |
| Hospital Parc Tauli | Sabadell | Spain |
| Hospital Universitario de Salamanca | Salamanca | Spain |
| Hospital Consorci Sanitari de Terrassa | Tarrasa | Spain |
| Hospital Clínico Universitario | Valencia | Spain |
| Hospital General Universitario | Valencia | Spain |
| Hospital La Fe | Valencia | Spain |
| Hospital Miguel Servet | Zaragoza | Spain |
Patients treated with placebo since 2 weeks before starting pegylated interferon and ribavirin until week 12 of antiviral treatment
| ANALYZED |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Escitalopram | Patients treated with 15 mg/day of Escitalopram since 2 weeks before starting pegylated interferon and ribavirin until week 12 of antiviral treatment |
| BG001 | Placebo | Patients treated with placebo since 2 weeks before starting pegylated interferon and ribavirin until week 12 of antiviral treatment |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Developed a Major Depressive Episode According to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Criteria During the First 12 Weeks of Antiviral Treatment. | At least five of the symptoms have been present during the same 1-week period: depressed mood, loss of interest or pleasure, weight or appetite changes, insomnia, agitation or retardation, fatigue, feelings of worthlessness or guilt, diminished ability to think or concentrate, recurrent thoughts of death. At least one of the symptoms is either depressed mood or loss of interest. Diagnoses were made by a trained psychiatrist who applied the mood disorders module from the Structured Clinical Interview for DSM-IV Axis I Disorders, non-patient edition (SCID-I/NP) at each study evaluation. | One of 67 patients allocated to the escitalopram group and 3 of 66 in placebo did not receive the first dose of study medications. Consequently, 66 patients treated with escitalopram and 63 with placebo were included in the intention to treat analysis, with a procedure of last observation carried forward (LOCF). | Posted | Number | Participants | First three months of interferon treatment. |
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| Primary | Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid). | Number of participants with negativization of serum hepatitis C Virus Ribonucleic Acid (HCV RNA) 6 months after concluding antiviral therapy (sustained viral response). Negativization was defined as the absence of detectable levels of serum HCV RNA using a polymerase chain reaction. | Patients with available data for viral response 6 months after completion of interferon treatment were compared between treatment groups. | Posted | Number | Participants | Six months after the end of interferon treatment |
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| Secondary | Total Score in the Montgomery-Asberg Depression Rating Scale | The MADRS is a 10-item scale, clinician-administered, which is sensitive to symptom change during antidepressant treatment. It has been frequently used to measure depressive symptoms during interferon-alpha therapy and exhibits improved internal consistency in patients with co-morbid medical conditions compared with other clinician-administered questionnaires. Items are rated on a scale of 0-6. Scores range from 0 to 60, higher scores meaning higher levels of depression. | Posted | Mean | Standard Error | Scores on a scale | 12 weeks after interferon treatment onset |
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| Secondary | Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale. | The Hospital Anxiety and Depression Scale (HADS) is 14-item scale, patient-administered, that allows two independent scores of depression and anxiety. It has been specially designed to apply in patients with comorbid medical conditions as it excludes somatic or vegetative symptoms from the depression subscale. We present data of de depression subscale. The seven-item Depression subscale yields a score of 0-21, with higher scores meaning higher levels of depressive symptoms. | Posted | Mean | Standard Error | Scores on a Scale | 12 weeks after interferon treatment onset |
|
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First three months of antiviral treatment
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Escitalopram | Patients treated with 15 mg/day of Escitalopram since 2 weeks before starting pegylated interferon and ribavirin until week 12 of antiviral treatment | 0 | 66 | 60 | 66 | ||
| EG001 | Placebo | Patients treated with placebo since 2 weeks before starting pegylated interferon and ribavirin until week 12 of antiviral treatment | 0 | 63 | 58 | 66 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | SNOMED CT | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | SNOMED CT | Non-systematic Assessment |
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| Breathing problems | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
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| Dizziness | General disorders | SNOMED CT | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
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| Fatigue | General disorders | SNOMED CT | Non-systematic Assessment |
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| Fever | General disorders | SNOMED CT | Non-systematic Assessment |
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| Flu-like symptoms | General disorders | SNOMED CT | Non-systematic Assessment |
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| Hair loss | Skin and subcutaneous tissue disorders | SNOMED CT | Non-systematic Assessment |
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| Headache | Nervous system disorders | SNOMED CT | Non-systematic Assessment |
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| Irritability | Psychiatric disorders | SNOMED CT | Non-systematic Assessment |
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| Leukopenia / neutropenia | Blood and lymphatic system disorders | SNOMED CT | Non-systematic Assessment |
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| Loss of appetite | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
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| Muscle or joint pain | Musculoskeletal and connective tissue disorders | SNOMED CT | Non-systematic Assessment |
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| Nausea or vomiting | Gastrointestinal disorders | SNOMED CT | Non-systematic Assessment |
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| Sexual dysfunction | Reproductive system and breast disorders | SNOMED CT | Non-systematic Assessment |
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| Sleep disorders | Psychiatric disorders | SNOMED CT | Non-systematic Assessment |
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The low depression rate found may have underpowered the study. Selection of a much less depressive sample than in other studies. Limitation to the first 12 weeks of antiviral treatment.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Crisanto Diez-Quevedo | Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona | +34934978814 | cdiezquevedo.germanstrias@gencat.cat |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D019698 | Hepatitis C, Chronic |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D006526 | Hepatitis C |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| D003909 | Dexetimide |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 | Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| Male |
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