Personalized Treatments for Depressive Symptoms in Patients With Advanced Heart Failure

We are doing this study to help patients, caregivers, and providers make decisions about how best to manage depressive symptoms in advanced heart failure. There are two evidence-based treatment approaches to treating depression in patients with advanced heart failure, behavioral action psychotherapy and treatment with anti-depressant medications. In this study we want to compare the effectiveness of these two treatment options to learn which treatment works better.

Study Overview

• Status: Completed
• Conditions: Depression; Heart Failure
• Intervention / Treatment: Drug: Medication Management; Behavioral: Behavioral Activation Therapy

Detailed Description

Aim 1: To compare the effectiveness of BA vs. MEDS, for depressed AHF patients. Hypothesis 1: Compared to depressed AHF patients who receive MEDS, patients receiving BA will have significantly greater improvements in the primary outcome of depressive symptom severity as measured with the PHQ-9 at 6-month follow-up. Significantly greater improvements will also be detected in the secondary outcomes of general physical and mental HRQoL (SF-12v2), heart failure-specific HRQoL (KCCQ), and caregiver burden (CBQ-HF) at 3, 6, and 12 months.

Aim 2: To compare the impact of BA vs. MEDS on disadvantageous outcomes of Morbidity (as evidenced by ED visits, hospital readmissions, total days in the hospital), and Mortality among depressed AHF patients.

Hypothesis 2: Compared to depressed AHF patients who receive MEDS, those receiving BA will have significantly less Morbidity (as evidenced by less frequent ED visits, lower readmission rates, fewer total days in the hospital), and reduced Mortality at the data collection points of 3, 6, and 12 months.

• Study Type: Interventional
• Enrollment (Actual): 494
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. HF New York Heart Association classes: II-IV.
2. Life expectancy of more than 6 months.
3. PHQ-9 score ≥10.
4. Diagnosis of Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), and Depressive Disorder Unspecified, as confirmed by the MINI 7.02.

Exclusion Criteria:

1. Imminent danger to self or others.
2. Cognitive impairments with a MOCA score of < 23.
3. Bipolar, Psychotic, and Substance-induced Disorders.
4. Patients in active treatment of depression who are already on antidepressants, psychotherapy, or both.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients: Medication Management (MEDS); The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.	Drug: Medication Management; Collaborative care model will be used. The medication management group will meet with the patient in a one 50 minute in person introductory antidepressant medication treatment session to educate the patient about depression and medication options. Patients will get prescribed a standard of care anti-depressant medication by treating physician, followed by 12 weekly follow up telephone visits, then on a monthly basis for 3 months, and then as needed thereafter.; Other Names: MEDS
Active Comparator: Patients: Behavioral Activation Therapy (BA); BA is an evidence-based psychotherapy with more than 25 randomized trials showing effectiveness in depression. The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.	Behavioral: Behavioral Activation Therapy; The therapy group will consist of an introductory in person 50-minute treatment session, followed by 12 weekly telephone 50-minute outpatient treatment sessions, then 3 monthly telephone 50-minute outpatient maintenance sessions. A typical BA session will last 50 minutes and include a review of the previous session and completed daily monitoring record forms, an in-depth discussion of life areas and value, and verbal reinforcement of activity engagement.; Other Names: BA
No Intervention: Caregivers: Medication Management (MEDS); Caregivers of patients receiving the the above described Medication Management (MEDS) intervention were monitored for caregiver burden at 3, 6, and 12 months.
No Intervention: Caregivers: Behavioral Activation Psychotherapy (BA); Caregivers of patients receiving the the above described Behavioral Activation Psychotherapy (BA) intervention were monitored for caregiver burden at 3, 6, and 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive Symptom Severity as Measured by the Patient Health Questionnaire (PHQ-9) Depression Scale Results at 6 Months Follow up	PHQ-9 is used to measure depressive symptoms severity. The PHQ-9 is a self-report instrument that corresponds with the validated Primary Care Evaluation of Mental Disorders PRIME-MD clinician-administered instrument. The PHQ-9 measures all nine dimensions of depression assessed in the DSM criteria for MDD on a 0-3 scale. Minimum score = 0 (no depression). Maximum scores = 21 (worst depression)	6 months from baseline enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the 12-item Questionnaire Used to Assess Health-related Quality of Life (SF-12v2) Scale Results	The SF-12v2 is a 12-item questionnaire used to assess Health-related Quality of Life (HRQoL) from the patient's perspective. The SF-12v2 consists of 12 questions from the SF-36 that evaluate the same eight health domains: physical function, the role-physical, bodily pain, general health, vitality, social function, the role-emotional, and mental health. The Physical Component Summary (PCS) and Mental Component Summary (MCS) scores are norm-based scores ranging from 0 to 100 calculated from the responses to the 12 questions using scoring software from QualityMetric.com. In the general US population, the mean normal score is 50, with a standard deviation (SD) of 10. Higher scores indicate better outcomes with better HRQoL. Health-related Quality of Life - Physical Health as measured by SF-12 physical component and Health	3 month, 6 month, and 12 months from baseline enrollment
Change From Baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ ) Scale Results.	The KCCQ is a 23-item, self-administered instrument that quantifies 6 domains and yields 2 summary scores. The 6 domains are physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The 2 summary scores are the Clinical Summary Score and the Overall Summary Score. The Clinical Summary score includes total symptom and physical function scores to correspond with NYHA Classification. The Overall Summary Score includes the total symptom, physical function, social limitations and quality of life scores. Domain scores and summary scores are scaled from the raw item scores using a software available from the authors (SPERTUSJ@UMKC.EDU) to a range from 0 (worst) to 100 (best), in which higher scores reflect better heart-failure-specific quality of life and health status. Heart failure-specific quality of life are measured by the KCCQ Overall Summary Score and the Clinical Summary Score .	3 month, 6 month, and 12 months from baseline enrollment
Change From Baseline on the Caregiver Burden Questionnaire-Heart Failure (CBQ-HF) Scale Results.	The Caregiver Burden Questionnaire - Heart Failure Version 3.0 (CBQ-HF) is a quantitative survey of 26 questions covering the past four weeks of the caregiver's experience is evaluated as caregiver burden. The scale uses a 5-point Likert severity scale (Not at all=0, A little=1, Somewhat=2, Quite a lot=3, A lot=4) assessing 4 domains of physical, emotional/psychological, social and lifestyle burdens. The score is summed from all the questions for each domain, and then summed to a total score that ranges from 0 (no burden) to 104 (worst burden), in which higher scores reflect worse outcomes of higher burden on the caregiver. We will measure the caregiver burden measured by the CBQ-HF.	3 month, 6 month, and 12 months from baseline enrollment
Mean Number of Emergency Department Visits	We recorded the number of emergency department visits.	3 month, 6 month, and 12 months from baseline enrollment
Mean Number of Readmissions (Hospitalization)	We recorded the number of readmissions to the hospital.	3 month, 6 month, and 12 months from baseline enrollment
If Hospitalized, Mean Number of Total Days in the Hospital	We recorded the number of total days in the hospital if they were hospitalized.	3 month, 6 month, and 12 months from baseline enrollment
Mortality Was Also Measured	We recorded mortality data on the patients.	3 month, 6 month, and 12 months from baseline enrollment

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Waguih W IsHak, MD, FAPA, Cedars-Sinai Medical Center

Publications and helpful links

General Publications

• IsHak WW, Korouri S, Darwish T, Vanle B, Dang J, Edwards G, Black JT, Aronow H, Kimchi A, Spiegel B, Hedrick R, Chernoff R, Diniz MA, Mirocha J, Manoukian V, Harold J, Ong MK, Wells K, Hamilton M, Danovitch I. Personalized treatments for depressive symptoms in patients with advanced heart failure: A pragmatic randomized controlled trial. PLoS One. 2021 Jan 7;16(1):e0244453. doi: 10.1371/journal.pone.0244453. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): May 6, 2022

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Heart Diseases; Cardiovascular Diseases; Heart Failure; Depression
• Other Study ID Numbers: Pro00054483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No