Chronic Heart Failure, Depression, Heart Failure, Congestive
Conditions
Keywords
Antidepressive Agents
Brief summary
This study will examine the effect of antidepressant medication on rates of death and disease in depressed people with chronic heart failure.
Detailed description
Comorbid depression in people with chronic medical illness is a serious public health concern. Depressive disorders lead to increased morbidity, mortality, and poorer outcomes in ischemic heart disease, a leading cause of chronic heart failure (CHF). Evidence suggests that a relationship exists between depression and CHF; studies that examine the way CHF is affected by depression treatments are needed. Participants in this study will be randomly assigned to receive either sertraline or placebo for 12 weeks. Assessments will be made at Weeks 2, 4, 6, 8, 10, and 12. Participants who do not respond to their treatment will have their medication dose adjusted following assessment. Interviews and rating scales will be used to assess depressive symptoms, cognitive status, psychiatric comorbidity, daily and chronic stress, and social support. A follow-up visit will take place 6 months, 1 year, 2 years, and 3 years after study completion.
Interventions
DRUGSertraline
Dosage ranging from 50 mg to 200 mg once a day
DRUGPlacebo
Dosage ranging from 50 mg to 200 mg once a day
Sponsors
National Institute of Mental Health (NIMH)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic heart failure * Diagnostic and Statistical Manual- Fourth Edition (DSM-IV) criteria for major depression * Current use of any antipsychotic medication at study entry
Exclusion criteria
* Life-threatening comorbidity with a 50% or higher likelihood of death within 1 year * History of psychoses, bipolar disorder, or severe personality disorder * History of alcohol or drug dependence in the last year * Severe physical disability that may interfere with the study * Neurological impairment * Active suicidal ideations * Current use of antidepressant medication(s) at the start of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms of Depression in Congestive Heart Failure Patients With Clinical Depression After Treatment With Sertraline or Placebo | Measured at Week 12 | Symptoms of depression (as measured by the Hamilton Depression Rating Scale, HDRS) in congestive heart failure patients with clinical depression after treatment with sertraline or placebo. The 17-item Hamilton Depression Rating Scale (HDRS) is a rater-administered assessment of depression severity, with total score ranges from 0 (not at all depressed) to 52 (most severely depressed). Change in depression was measured as the difference between the 12-week HDRS scores and the baseline HDRS scores. Thus, a negative value reflects an improvement in depressive symptoms over the 12-week period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Measured at Week 12 | Composite cardiovascular scores are calculated for each participant using recorded cardiac events, morbidity/mortality, rehospitalization, and discontinuation due to cardiovascular events. Composite score is compared for sertraline and placebo treatment groups. |
Countries
United States
Participant flow
Recruitment details
Recruitment began in November, 2003 and concluded in March, 2008. Subjects were recruited from cardiology inpatient units as well as outpatient cardiology clinics.
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Participants will take sertraline for 12 weeks | 234 |
| Placebo Participants will take placebo for 12 weeks | 235 |
| Total | 469 |
Baseline characteristics
| Characteristic | Sertraline | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 103 Participants | 88 Participants | 191.0 Participants |
| Age, Categorical Between 18 and 65 years | 131 Participants | 147 Participants | 278.0 Participants |
| Age Continuous | 62.9 years STANDARD_DEVIATION 10.5 | 61.4 years STANDARD_DEVIATION 11.1 | 62.1 years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 101 Participants | 89 Participants | 190.0 Participants |
| Sex: Female, Male Male | 133 Participants | 146 Participants | 279.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 234 | 23 / 235 |
| serious Total, serious adverse events | 57 / 234 | 63 / 235 |
Outcome results
Primary
Symptoms of Depression in Congestive Heart Failure Patients With Clinical Depression After Treatment With Sertraline or Placebo
Symptoms of depression (as measured by the Hamilton Depression Rating Scale, HDRS) in congestive heart failure patients with clinical depression after treatment with sertraline or placebo. The 17-item Hamilton Depression Rating Scale (HDRS) is a rater-administered assessment of depression severity, with total score ranges from 0 (not at all depressed) to 52 (most severely depressed). Change in depression was measured as the difference between the 12-week HDRS scores and the baseline HDRS scores. Thus, a negative value reflects an improvement in depressive symptoms over the 12-week period.
Time frame: Measured at Week 12
Population: Analysis was based on intent to treat (ITT), using random coefficient modeling.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Symptoms of Depression in Congestive Heart Failure Patients With Clinical Depression After Treatment With Sertraline or Placebo | -7.1 HDRS Change Score | Standard Deviation 0.5 |
| Placebo | Symptoms of Depression in Congestive Heart Failure Patients With Clinical Depression After Treatment With Sertraline or Placebo | -6.8 HDRS Change Score | Standard Deviation 0.5 |
Comparison: A hierarchical mixed model was used, analyzing the fixed effects of treatment, the natural log of time, natural log of time squared, the interactions of time and time squared with treatment and site, as well as the random effects of patient, patient-by-time, and square of patient-by-time.p-value: 0.89Mixed Models Analysis
Secondary
Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo.
Composite cardiovascular scores are calculated for each participant using recorded cardiac events, morbidity/mortality, rehospitalization, and discontinuation due to cardiovascular events. Composite score is compared for sertraline and placebo treatment groups.
Time frame: Measured at Week 12
Population: Analysis was based on intent to treat (ITT).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sertraline | Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Cardiovascular Status Worsened | 29.9 percentage of participants |
| Sertraline | Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Cardiovascular Status Improved | 40.6 percentage of participants |
| Sertraline | Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Cardiovascular Status Unchanged | 29.5 percentage of participants |
| Placebo | Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Cardiovascular Status Worsened | 31.1 percentage of participants |
| Placebo | Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Cardiovascular Status Improved | 43.8 percentage of participants |
| Placebo | Percentage of Cardiac Events and Morbidity / Mortality, Including Rehospitalization, in Congestive Heart Failure Patients With Depression After Treatment With Sertraline or Placebo. | Cardiovascular Status Unchanged | 25.1 percentage of participants |
Comparison: Tests for differences of proportions were used to examine the composite cardiovascular status outcome at the end of acute treatment. Chi-square tests were used to test for overall treatment differences, with a Mantel Haenszel test performed to examine treatment differences when controlling for clinical site. The primary analyses were conducted on the tri-level cardiovascular status outcome.p-value: 0.78Cochran-Mantel-Haenszel