Clinical trial NCT06161987: EACH-ADHF: Early Comprehensive Rehabilitation in Patients With ADHF
Official title: Efficacy and Safety of Early Comprehensive Rehabilitation in Patients With ADHF, A Multicenter, Randomized, Controlled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Decompensated Heart Failure
Keywords: Acute decompensated heart failure
Early comprehensive rehabilitation
Inspiratory muscle training
Exercise training
KCCQ
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2023-12-08
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: EACH-ADHF: Early Comprehensive Rehabilitation in patients with ADHF study is a multi-center, parallel-group, randomized controlled trial designed to evaluate the effects of the early comprehensive rehabilitation including exercise and inspiratory muscle training, over a period of 6 weeks, on the quality of life of patients with ADHF.

Detailed description: Guangdong Provincial People's Hospital will be the lead center, with an additional 12 hospitals designated as satellite centers for the study. To sum up, these centers will recruit a total of 140 consenting patients. Following informed consent and baseline testing, the participants will be randomized in a 1:1 fashion to receive a 6-week progressive, comprehensive exercise training and inspiratory muscle training or attention control.

The intervention group will receive an 6-week exercise program consisting of endurance, resistance, balance, mobility, and inspiratory muscle training. The comprehensive rehabilitation will begin during the patient's stay and continue to the outpatient clinic. The control group will receive usual care with bi-weekly contact from study personnel. The primary outcomes of the study are improvements in the summary score of KCCQ and PImax%pred, while secondary endpoints include the impact on physical function, cardiac function, psychological status, and major adverse cardiovascular events (MACE). Additionally, the study will also explore the effects of comprehensive rehabilitation on hospital readmission and mortality rates, with follow-up assessments planned up to 6 months after discharge.

Eligibility criteria: Inclusion Criteria:

1. Age between 18-80
2. At least one symptom of heart failure upon admission:

   Dyspnea at rest or with exertion, orthopnea, paroxysmal nocturnal dyspnea or exertional fatigue.
3. At least two of the signs of heart failure (HF):

   Distended jugular veins, enlarged cardiac silhouette, apex beat displacement, third heart sound, or increased jugular venous pressure/central venous pressure/pulmonary capillary wedge pressure.

   Pulmonary edema or pulmonary congestion (rales or chest X-ray/CT evidence of pulmonary congestion).

   Peripheral edema. Elevated B-type natriuretic peptide (\>100 pg/ml) or elevated NT-proBNP (\>300 pg/ml).
4. Able to independently perform basic activities of daily living before admission.
5. Able to complete the baseline assessment and initiate the specified treatment.
6. Able to walk 4 meters at the time of enrollment (assistive devices may be used).
7. Agree to participate in this study, sign a written informed consent form, and is willing to cooperate with follow-up.

Exclusion Criteria:

1. Acute heart failure caused by acute myocardial infarction.
2. Severe aortic valve stenosis.
3. Hemodynamic instability caused by poorly controlled arrhythmias.
4. Severe heart failure and high-degree atrioventricular block, and inadequate heart rate response to pacing during exercise.
5. Isolated pulmonary hypertension.
6. Poorly controlled symptomatic orthostatic hypotension.
7. Hypertrophic obstructive cardiomyopathy.
8. Stage 5 chronic kidney failure, defined as glomerular filtration rate \<15 ml/(min·1.73m²) or requiring dialysis.
9. Undergoing screening tests with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than or equal to 5 times the upper limit of the normal range defined by the center.
10. Awaiting a heart transplant or ventricular assist device implantation within six months, or having received a heart transplant.
11. A history of chronic lung disease except for COPD, previous lung surgery, or diseases affecting lung function, such as scoliosis.
12. Late-stage diseases other than heart failure.
13. Any medical history that could potentially affect protocol compliance, such as severe mental disorders, severe cognitive impairment, substance abuse, or addiction.
14. Severe language, psychological, or physical disabilities that prevent their participation in the program.
15. Pregnant or lactating women, or those of childbearing potential who are unwilling or unable to use effective contraceptive measures.
16. Involved in other interventional clinical trials.
17. Patients deemed unfit for participation in this study by the researchers.

Primary outcomes:
measure: Score of Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Baseline and Week 6
measure: Maximal Inspiratory Pressure as a Percentage of Predicted Value (PImax%pred)
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: Score of Short Physical Performance Battery (SPPB)
timeFrame: Baseline and Week 6
measure: Score of Frailty
timeFrame: Baseline and Week 6
measure: Pulmonary Function
timeFrame: Baseline and Week 6
measure: Rate of All-Cause Rehospitalization
timeFrame: Month 6
Other outcomes:
measure: Score of Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12)
timeFrame: Baseline and Week 6
measure: Score of Anxiety
timeFrame: Baseline and Week 6
measure: Score of Depression
timeFrame: Baseline and Week 6
measure: 6-minute Walk Distance
timeFrame: Baseline and Week 6
measure: Left ventricular ejection fraction (LVEF)
timeFrame: Baseline and Week 6
measure: Left ventricular end-diastolic volume (LVEDV)
timeFrame: Baseline and Week 6
measure: Left ventricular end-systolic volume (LVESV)
timeFrame: Baseline and Week 6
measure: Rate of All-cause Rehospitalizations
timeFrame: Month 3, 6
measure: Rate of All-cause Composite Rehospitalization and Death
timeFrame: Month 3, 6
measure: Assessment of diaphragmatic excursion
timeFrame: Baseline and Week 6
measure: Assessment of diaphragm thickness
timeFrame: Baseline and Week 6
measure: The concentration of N-Terminal Pro-Brain Natriuretic Peptide （BNP/NT-proBNP）
timeFrame: Baseline and Week 6
measure: Incidence of adverse events and serious adverse events
timeFrame: Month 3, 6
measure: Incidence of Cardiovascular-related Composite Rehospitalization and Death
timeFrame: Month 3, 6
measure: Proteomics analysis
timeFrame: Baseline and Week 6
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
Study officials:
References:
citation: 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.
citation: Mudge AM, Denaro CP, Scott AC, Meyers D, Adsett JA, Mullins RW, Suna JM, Atherton JJ, Marwick TH, Scuffham P, O'Rourke P. Addition of Supervised Exercise Training to a Post-Hospital Disease Management Program for Patients Recently Hospitalized With Acute Heart Failure: The EJECTION-HF Randomized Phase 4 Trial. JACC Heart Fail. 2018 Feb;6(2):143-152. doi: 10.1016/j.jchf.2017.11.016.
citation: Reeves GR, Whellan DJ, Duncan P, O'Connor CM, Pastva AM, Eggebeen JD, Hewston LA, Morgan TM, Reed SD, Rejeski WJ, Mentz RJ, Rosenberg PB, Kitzman DW; REHAB-HF Trial Investigators. Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial: Design and rationale. Am Heart J. 2017 Mar;185:130-139. doi: 10.1016/j.ahj.2016.12.012. Epub 2016 Dec 28.
citation: Laoutaris ID, Piotrowicz E, Kallistratos MS, Dritsas A, Dimaki N, Miliopoulos D, Andriopoulou M, Manolis AJ, Volterrani M, Piepoli MF, Coats AJS, Adamopoulos S; ARISTOS-HF trial (Aerobic, Resistance, InSpiratory Training OutcomeS in Heart Failure) Investigators. Combined aerobic/resistance/inspiratory muscle training as the 'optimum' exercise programme for patients with chronic heart failure: ARISTOS-HF randomized clinical trial. Eur J Prev Cardiol. 2021 Dec 29;28(15):1626-1635. doi: 10.1093/eurjpc/zwaa091.
citation: Wu L, Li J, Chen L, Xue M, Zheng Y, Meng F, Jiang H, Shi Z, Zhang P, Dai C. The Efficacy and Safety of Phase I Cardiac Rehabilitation in Patients Hospitalized in Cardiac Intensive Care Unit With Acute Decompensated Heart Failure: A Study Protocol for a Randomized, Controlled, Clinical Trial. Front Cardiovasc Med. 2022 Mar 8;9:788503. doi: 10.3389/fcvm.2022.788503. eCollection 2022.
citation: McNallan SM, Chamberlain AM, Gerber Y, Singh M, Kane RL, Weston SA, Dunlay SM, Jiang R, Roger VL. Measuring frailty in heart failure: a community perspective. Am Heart J. 2013 Oct;166(4):768-74. doi: 10.1016/j.ahj.2013.07.008. Epub 2013 Sep 17.
citation: Chiappa GR, Roseguini BT, Vieira PJ, Alves CN, Tavares A, Winkelmann ER, Ferlin EL, Stein R, Ribeiro JP. Inspiratory muscle training improves blood flow to resting and exercising limbs in patients with chronic heart failure. J Am Coll Cardiol. 2008 Apr 29;51(17):1663-71. doi: 10.1016/j.jacc.2007.12.045.
citation: Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
citation: Spertus JA, Jones PG, Kim J, Globe D. Validity, reliability, and responsiveness of the Kansas City Cardiomyopathy Questionnaire in anemic heart failure patients. Qual Life Res. 2008 Mar;17(2):291-8. doi: 10.1007/s11136-007-9302-5. Epub 2007 Dec 29.
citation: Takada S, Kondo T, Yasunaga M, Watanabe S, Kinoshita H, Fukuhara S, Yamamoto Y. Early rehabilitation in older patients hospitalized with acute decompensated heart failure: A retrospective cohort study. Am Heart J. 2020 Dec;230:44-53. doi: 10.1016/j.ahj.2020.09.009. Epub 2020 Sep 19.