Acute Decompensated Heart Failure
Conditions
Keywords
heart failure
Brief summary
REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients, is a multicenter, randomized, attention-controlled, single-blind trial designed to examine the hypothesis that, in addition to standard care, a novel, tailored, progressive, multi-domain rehabilitation intervention administered to older patients with acute decompensated heart failure (ADHF) beginning early during hospitalization and continuing for 12 weeks will improve physical function and key clinical outcomes, including the rate of rehospitalization.
Detailed description
There will be three lead centers, Wake Forest Baptist Health along with Thomas Jefferson University and Hospital-Co-Investigator Dr. David Whellan, and Duke University Medical Center-Co-Investigator Dr. Christopher O'Connor. Each center may recruit up to 3 geographically close, tightly affiliated 'satellite' sites under their management and budgetary control. Together, these sites will recruit a total of 352 consenting patients ≥ 60 years old hospitalized with ADHF. Following informed consent and baseline testing, the participants will be randomized in a 1:1 fashion to receive a 12-week novel, progressive, multi-domain rehabilitation and exercise training intervention or attention control. The multi-domain rehabilitation intervention will include endurance, mobility, strength, and balance training and will be tailored based on participant performance in each of these domains. It will begin upon randomization during the hospitalization and will continue 3 times per week in an outpatient setting. Participants randomized to the attention control arm will receive all services ordered by their primary physician and will be contacted bi-weekly by study staff. All participants will undergo measures of physical function and quality of life at baseline, 1 month, and 3 months. Clinical events will be monitored for 6 months following the index hospitalization.
Interventions
BEHAVIORALmulti-domain rehabilitation intervention
Individual, tailored, progressive physical function rehabilitation intervention
BEHAVIORALAttention Control
Usual care with bi-weekly contact from study staff
Sponsors
National Institute on Aging (NIA)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 60 years old * In the hospital setting \>24 hours for the management of ADHF, or diagnosed with ADHF after being hospitalized for another reason. ADHF will be confirmed by the study physician, and will be defined according to the Food and Drug Administration definition of hospitalized heart failure as a combination of symptoms, signs, and HF-specific medical treatments.
Exclusion criteria
* Acute myocardial infarction * Planned discharge other than to home or a facility where the participant will live independently * Already actively participating in formal, facility-based cardiac rehabilitation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Physical Performance Battery (SPPB) at Month 3 | Month 3 | The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Rehospitalization | Month 6 | Number of all-cause rehospitalizations 6 months from index hospital discharge. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frailty Status (Fried Frailty Criteria) at Month 3 | Month 3 | Exploratory outcome. Frailty is assessed by the Fried criteria consisting of 5 components: low physical activity, exhaustion, weakness, slowness, and unintentional weight loss. Presence of 3 or more Fried criteria indicates frailty, 1-2 criteria indicates pre-frailty, and 0 criteria indicates no frailty. |
| Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | Month 3 | Exploratory outcome. The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status. |
| Physical Limitation as Assessed by the KCCQ Physical Limitation Score | Month 3 | Exploratory outcome. The Physical Limitation Score of the KCCQ questionnaire is a subscore evaluating disease-specific physical limitation. Scores range 0-100 with a higher score indicating less physical limitation. |
| Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12) | Month 3 | Exploratory outcome. The SF-12 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status. |
| Quality of Life Assessed by the EuroQol 5-dimension 5-level (EQ-5D-5L) | Month 6 | Exploratory outcome. The EQ-5D-5L is a quality of life tool with 5 components designed to detect health utilities: mobility, usual activities, self-care, pain/discomfort, and anxiety/depression. All components are rated on a scale of 1-5 with higher scores indicating worse health status. |
| Depression Measured by the Geriatric Depression Scale | Month 3 | Exploratory outcome. The Geriatric Depression Scale is a 15-item questionnaire evaluating depressive symptoms. Scores range from 0-15 with a higher score indicating more severe depressive symptoms. |
| Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA) | Month 3 | Exploratory outcome. The Montreal Cognitive Assessment is a tool for assessing multiple domains of cognitive function. Scores range 0-30 with higher scores indicating better cognitive function. A score greater than or equal to 26 is considered normal cognitive function. |
| All-cause Rehospitalizations at Month 1 | Month 1 | Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge. |
| All-cause Rehospitalizations at Month 3 | Month 3 | Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization |
| All-cause Combined Rehospitalization and Death at Month 6 | Month 6 | Exploratory outcome. Combined number of all-cause rehospitalizations and death 6 months after discharge from index hospitalization |
| Heart Failure Rehospitalizations at Month 6 | Month 6 | Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization |
| 6-minute Walk Distance | Month 3 | Exploratory outcome. Distance walked in 6 minutes. |
| Facility-free Days Alive | Month 6 | Exploratory outcomes. Total days alive spent outside of hospital, observation unit, acute rehab setting, and skilled nursing facility 6 months after discharge from index hospitalization. |
| Emergency Department Visits | Month 6 | Exploratory outcomes. Number of emergency department visits after 6 months from hospital discharge |
| Observation Unit Stays <24 Hours | Month 6 | Exploratory outcome. Number of observation unit stays \<24 hours 6 months after discharge from index hospitalization |
| Unscheduled Urgent Medical Visits | Month 6 | Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization |
| Global Rank Score of Short Physical Performance Battery Score + All-cause Rehospitalization + Death | Month 6 | Exploratory outcome. The global rank composite outcome combines non-commensurate endpoints including death, number of all-cause rehospitalizations, and month 3 SPPB into a single non-parametric outcome in a hierarchical manner with death being ranked first and SPPB being ranked last. Participants are ranked from the most adverse response (lowest rank) to the most favorable response (highest rank). |
| Placement at Skilled Nursing Facility | Month 6 | Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization. |
| Physical Activity Assessed by Accelerometry | Month 6 | Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day. |
| Generalized Optimism Assessed by the Life Orientation Test-Revised | Month 3 | Exploratory outcome. The Life Orientation Test-Revised is a assessment of generalized optimism scored on a scale of 0-24 with higher scores indicating higher optimism. |
| Economic Analysis | Month 6 | Assess direct medical costs, direct non-medical costs, indirect patient time costs, short-term cost-analysis, long-term cost analysis, and sustainability of the intervention. |
| Biomarkers | Month 3 | Two well-accepted biomarkers of HF disease severity and prognosis, NT-proBNP and galectin-3, and increased biomarkers in older HF patients Tumor necrosis factor alpha, C-reactive protein, and interleukin-6. |
| Hospitalization Days Post-randomization | Month 6 | Exploratory outcome. Total days spent hospitalized after date of randomization. |
| Handgrip Strength | Month 3 | Exploratory outcome. Handgrip strength is measured in kilograms by a handgrip dynamometer. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Attention Control Usual care group with bi-weekly contact | 174 |
| Rehabilitation Intervention Individual, tailored, progressive, multi-domain physical function rehabilitation intervention | 175 |
| Total | 349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 16 | 21 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Attention Control | Total | Rehabilitation Intervention |
|---|---|---|---|
| Age, Continuous | 72.2 years STANDARD_DEVIATION 7.7 | 72.7 years STANDARD_DEVIATION 8.1 | 73.1 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 170 Participants | 342 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 81 Participants | 154 Participants | 73 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 83 Participants | 173 Participants | 90 Participants |
| Sex: Female, Male Female | 98 Participants | 183 Participants | 85 Participants |
| Sex: Female, Male Male | 76 Participants | 166 Participants | 90 Participants |
| Short Physical Performance Battery | 6.1 Score on a Scale STANDARD_DEVIATION 2.6 | 6.1 Score on a Scale STANDARD_DEVIATION 2.7 | 6.0 Score on a Scale STANDARD_DEVIATION 2.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 174 | 21 / 175 |
| other Total, other adverse events | 69 / 174 | 60 / 175 |
| serious Total, serious adverse events | 115 / 174 | 106 / 175 |
Outcome results
Primary
Short Physical Performance Battery (SPPB) at Month 3
The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.
Time frame: Month 3
Population: Analysis completed on all participants alive with Month 3 SPPB obtained (n=304).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Attention Control | Short Physical Performance Battery (SPPB) at Month 3 | 6.9 score on a scale | Standard Error 0.2 |
| Rehabilitation Intervention | Short Physical Performance Battery (SPPB) at Month 3 | 8.3 score on a scale | Standard Error 0.2 |
p-value: <0.000195% CI: [0.9, 2]joint model
Secondary
All-Cause Rehospitalization
Number of all-cause rehospitalizations 6 months from index hospital discharge.
Time frame: Month 6
Population: All participants, regardless of participation in the intervention or Month 3 follow-up were followed for all-cause rehospitalizations. Analysis completed on all participants, including deaths, except participants lost to follow-up (n=1) and participants withdrawn from study (n=1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Attention Control | All-Cause Rehospitalization | 213 rehospitalizations |
| Rehabilitation Intervention | All-Cause Rehospitalization | 194 rehospitalizations |
p-value: 0.5995% CI: [0.66, 1.19]Joint Model
Other Pre-specified
6-minute Walk Distance
Exploratory outcome. Distance walked in 6 minutes.
Time frame: Month 3
Other Pre-specified
All-cause Combined Rehospitalization and Death at Month 6
Exploratory outcome. Combined number of all-cause rehospitalizations and death 6 months after discharge from index hospitalization
Time frame: Month 6
Other Pre-specified
All-cause Rehospitalizations at Month 1
Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge.
Time frame: Month 1
Other Pre-specified
All-cause Rehospitalizations at Month 3
Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization
Time frame: Month 3
Other Pre-specified
Biomarkers
Two well-accepted biomarkers of HF disease severity and prognosis, NT-proBNP and galectin-3, and increased biomarkers in older HF patients Tumor necrosis factor alpha, C-reactive protein, and interleukin-6.
Time frame: Month 3
Other Pre-specified
Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)
Exploratory outcome. The Montreal Cognitive Assessment is a tool for assessing multiple domains of cognitive function. Scores range 0-30 with higher scores indicating better cognitive function. A score greater than or equal to 26 is considered normal cognitive function.
Time frame: Month 3
Other Pre-specified
Depression Measured by the Geriatric Depression Scale
Exploratory outcome. The Geriatric Depression Scale is a 15-item questionnaire evaluating depressive symptoms. Scores range from 0-15 with a higher score indicating more severe depressive symptoms.
Time frame: Month 3
Other Pre-specified
Economic Analysis
Assess direct medical costs, direct non-medical costs, indirect patient time costs, short-term cost-analysis, long-term cost analysis, and sustainability of the intervention.
Time frame: Month 6
Other Pre-specified
Emergency Department Visits
Exploratory outcomes. Number of emergency department visits after 6 months from hospital discharge
Time frame: Month 6
Other Pre-specified
Facility-free Days Alive
Exploratory outcomes. Total days alive spent outside of hospital, observation unit, acute rehab setting, and skilled nursing facility 6 months after discharge from index hospitalization.
Time frame: Month 6
Other Pre-specified
Frailty Status (Fried Frailty Criteria) at Month 3
Exploratory outcome. Frailty is assessed by the Fried criteria consisting of 5 components: low physical activity, exhaustion, weakness, slowness, and unintentional weight loss. Presence of 3 or more Fried criteria indicates frailty, 1-2 criteria indicates pre-frailty, and 0 criteria indicates no frailty.
Time frame: Month 3
Other Pre-specified
Generalized Optimism Assessed by the Life Orientation Test-Revised
Exploratory outcome. The Life Orientation Test-Revised is a assessment of generalized optimism scored on a scale of 0-24 with higher scores indicating higher optimism.
Time frame: Month 3
Other Pre-specified
Global Rank Score of Short Physical Performance Battery Score + All-cause Rehospitalization + Death
Exploratory outcome. The global rank composite outcome combines non-commensurate endpoints including death, number of all-cause rehospitalizations, and month 3 SPPB into a single non-parametric outcome in a hierarchical manner with death being ranked first and SPPB being ranked last. Participants are ranked from the most adverse response (lowest rank) to the most favorable response (highest rank).
Time frame: Month 6
Other Pre-specified
Handgrip Strength
Exploratory outcome. Handgrip strength is measured in kilograms by a handgrip dynamometer.
Time frame: Month 3
Other Pre-specified
Heart Failure Rehospitalizations at Month 6
Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization
Time frame: Month 6
Other Pre-specified
Hospitalization Days Post-randomization
Exploratory outcome. Total days spent hospitalized after date of randomization.
Time frame: Month 6
Other Pre-specified
Observation Unit Stays <24 Hours
Exploratory outcome. Number of observation unit stays \<24 hours 6 months after discharge from index hospitalization
Time frame: Month 6
Other Pre-specified
Physical Activity Assessed by Accelerometry
Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day.
Time frame: Month 6
Other Pre-specified
Physical Limitation as Assessed by the KCCQ Physical Limitation Score
Exploratory outcome. The Physical Limitation Score of the KCCQ questionnaire is a subscore evaluating disease-specific physical limitation. Scores range 0-100 with a higher score indicating less physical limitation.
Time frame: Month 3
Other Pre-specified
Placement at Skilled Nursing Facility
Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization.
Time frame: Month 6
Other Pre-specified
Quality of Life Assessed by the EuroQol 5-dimension 5-level (EQ-5D-5L)
Exploratory outcome. The EQ-5D-5L is a quality of life tool with 5 components designed to detect health utilities: mobility, usual activities, self-care, pain/discomfort, and anxiety/depression. All components are rated on a scale of 1-5 with higher scores indicating worse health status.
Time frame: Month 6
Other Pre-specified
Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Exploratory outcome. The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status.
Time frame: Month 3
Other Pre-specified
Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12)
Exploratory outcome. The SF-12 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status.
Time frame: Month 3
Other Pre-specified
Unscheduled Urgent Medical Visits
Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization
Time frame: Month 6