A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF)

REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients

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.

Study Overview

• Status: Completed
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Behavioral: Attention Control; Behavioral: multi-domain rehabilitation intervention

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.

• Study Type: Interventional
• Enrollment (Actual): 349
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Attention Control; Usual care group with bi-weekly contact from study staff	Behavioral: Attention Control; Usual care with bi-weekly contact from study staff
Active Comparator: multi-domain rehabilitation intervention; Individual, tailored, progressive, physical function rehabilitation intervention	Behavioral: multi-domain rehabilitation intervention; Individual, tailored, progressive physical function rehabilitation intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Rehospitalization	Number of all-cause rehospitalizations 6 months from index hospital discharge.	Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute Walk Distance	Exploratory outcome. Distance walked in 6 minutes.	Month 3
Handgrip Strength	Exploratory outcome. Handgrip strength is measured in kilograms by a handgrip dynamometer.	Month 3
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.	Month 3
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.	Month 3
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.	Month 3
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.	Month 3
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.	Month 6
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.	Month 3
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.	Month 3
All-cause Rehospitalizations at Month 1	Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge.	Month 1
All-cause Rehospitalizations at Month 3	Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization	Month 3
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	Month 6
Heart Failure Rehospitalizations at Month 6	Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization	Month 6
Hospitalization Days Post-randomization	Exploratory outcome. Total days spent hospitalized after date of randomization.	Month 6
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.	Month 6
Emergency Department Visits	Exploratory outcomes. Number of emergency department visits after 6 months from hospital discharge	Month 6
Observation Unit Stays <24 Hours	Exploratory outcome. Number of observation unit stays <24 hours 6 months after discharge from index hospitalization	Month 6
Unscheduled Urgent Medical Visits	Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization	Month 6
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).	Month 6
Placement at Skilled Nursing Facility	Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization.	Month 6
Physical Activity Assessed by Accelerometry	Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day.	Month 6
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.	Month 3
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.	Month 6
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.	Month 3

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• Nelson MB, Shiroma EJ, Kitzman DW, Duncan PW, Reeves GR, Whellan DJ, Mentz RJ, Chen H, Pastva AM. Physical activity and relationship to physical function, quality of life, and cognitive function in older patients with acute decompensated heart failure. Am Heart J. 2023 Feb;256:85-94. doi: 10.1016/j.ahj.2022.11.002. Epub 2022 Nov 11.
• Whellan D, McCarey MM, Chen H, Nelson MB, Pastva AM, Duncan P, Mentz RJ, Kitzman DW, Reeves G, Reed SD. Quality of Life Trajectory and Its Mediators in Older Patients With Acute Decompensated Heart Failure Receiving a Multi-Domain Rehabilitation Intervention: Results From the Rehabilitation Therapy in Older Acute Heart Failure Patients Trial. Circ Heart Fail. 2022 Dec;15(12):e009695. doi: 10.1161/CIRCHEARTFAILURE.122.009695. Epub 2022 Nov 8.
• Peters AE, Kitzman DW, Chen H, Nelson MB, Pastva AM, Duncan PW, Reeves GR, Upadhya B, Whellan DJ, Mentz RJ. Obesity Status and Physical Rehabilitation in Older Patients Hospitalized With Acute HF: Insights From REHAB-HF. JACC Heart Fail. 2022 Dec;10(12):918-927. doi: 10.1016/j.jchf.2022.07.008. Epub 2022 Sep 7.
• Nelson MB, Gilbert ON, Duncan PW, Kitzman DW, Reeves GR, Whellan DJ, Mentz RJ, Chen H, Hewston LA, Taylor KM, Pastva AM. Intervention Adherence in REHAB-HF: Predictors and Relationship With Physical Function, Quality of Life, and Clinical Events. J Am Heart Assoc. 2022 Jun 7;11(11):e024246. doi: 10.1161/JAHA.121.024246. Epub 2022 Jun 3.
• Mentz RJ, Whellan DJ, Reeves GR, Pastva AM, Duncan P, Upadhya B, Nelson MB, Chen H, Reed SD, Rosenberg PB, Bertoni AG, O'Connor CM, Kitzman DW. Rehabilitation Intervention in Older Patients With Acute Heart Failure With Preserved Versus Reduced Ejection Fraction. JACC Heart Fail. 2021 Oct;9(10):747-757. doi: 10.1016/j.jchf.2021.05.007. Epub 2021 Jul 7.
• Kitzman DW, Whellan DJ, Duncan P, Pastva AM, Mentz RJ, Reeves GR, Nelson MB, Chen H, Upadhya B, Reed SD, Espeland MA, Hewston L, O'Connor CM. Physical Rehabilitation for Older Patients Hospitalized for Heart Failure. N Engl J Med. 2021 Jul 15;385(3):203-216. doi: 10.1056/NEJMoa2026141. Epub 2021 May 16.
• Warraich HJ, Kitzman DW, Whellan DJ, Duncan PW, Mentz RJ, Pastva AM, Nelson MB, Upadhya B, Reeves GR. Physical Function, Frailty, Cognition, Depression, and Quality of Life in Hospitalized Adults >/=60 Years With Acute Decompensated Heart Failure With Preserved Versus Reduced Ejection Fraction. Circ Heart Fail. 2018 Nov;11(11):e005254. doi: 10.1161/CIRCHEARTFAILURE.118.005254.
• Reeves GR, Whellan DJ, O'Connor CM, Duncan P, Eggebeen JD, Morgan TM, Hewston LA, Pastva A, Patel MJ, Kitzman DW. A Novel Rehabilitation Intervention for Older Patients With Acute Decompensated Heart Failure: The REHAB-HF Pilot Study. JACC Heart Fail. 2017 May;5(5):359-366. doi: 10.1016/j.jchf.2016.12.019. Epub 2017 Mar 8.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): July 27, 2020

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (Estimate): July 21, 2014

Study Record Updates

• Last Update Posted (Actual): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: IRB00028221; R01AG045551 (U.S. NIH Grant/Contract)

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: No
• Studies a U.S. FDA-regulated device product: No