EACH-ADHF: Early Comprehensive Rehabilitation in Patients With ADHF

Acute Decompensated Heart Failure Clinical Trial

— EACH-ADHF  

Official title:

Efficacy and Safety of Early Comprehensive Rehabilitation in Patients With ADHF, A Multicenter, Randomized, Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06161987
• Other study ID #: KY-Q-2022-487-03
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: December 2023
• Source: Guangdong Provincial People's Hospital
• Contact: Huan Ma, PhD
• Phone: +86 15078755932
• Email: mahuandoctor[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: June 30, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Behavioral:
• Early comprehensive rehabilitation
Patients randomized to the rehabilitation intervention group will be offered comprehensive rehabilitation plan containing 18 sessions of a structured outpatient-based exercise program over 6 weeks (3 times per week).

Locations

Country	Name	City	State
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Provincial People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

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. — View 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. 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. Erratum In: Circulation. 2022 May 3;145(18):e1033. Circulation. 2022 Sep 27;146(13):e185. Circulation. 2023 Apr 4;147(14):e674. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Score of Quality of Life Measured by Short Form 12 Item Questionnaire (SF-12)	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.	Baseline and Week 6
Other	Score of Anxiety	Anxiety is assessed by General Anxiety Disorder-7. Score ranges from 0 to 21 points, with higher scores indicating more severe anxiety.	Baseline and Week 6
Other	Score of Depression	Depression is assessed by Patient Health Questionnaire-9. Score of Patient Health Questionnaire-9 ranges from 0 to 27 points, with higher scores indicating more severe mood depression.	Baseline and Week 6
Other	6-minute Walk Distance	Distance walked in 6 minutes.	Baseline and Week 6
Other	Left ventricular ejection fraction (LVEF)	Using Echocardiography to assess the left ventricular ejection fraction (LVEF)	Baseline and Week 6
Other	Left ventricular end-diastolic volume (LVEDV)	Using Echocardiography to assess the left ventricular end-diastolic volume (LVEDV)	Baseline and Week 6
Other	Left ventricular end-systolic volume (LVESV)	Using Echocardiography to assess the left ventricular end-systolic volume (LVESV)	Baseline and Week 6
Other	Rate of All-cause Rehospitalizations	Number of all-cause rehospitalizations at 3 and 6 months from hospital discharge.	Month 3, 6
Other	Rate of All-cause Composite Rehospitalization and Death	Composite number of all-cause rehospitalizations and death at 3 and 6 months from hospital discharge.	Month 3, 6
Other	Assessment of diaphragmatic excursion	Using Ultrasound of diaphragm to assess diaphragm excursion.	Baseline and Week 6
Other	Assessment of diaphragm thickness	Using Ultrasound of diaphragm to assess diaphragm thickness	Baseline and Week 6
Other	The concentration of N-Terminal Pro-Brain Natriuretic Peptide (BNP/NT-proBNP)	The concentration of N-Terminal Pro-Brain Natriuretic Peptide (BNP/NT-proBNP)	Baseline and Week 6
Other	Incidence of adverse events and serious adverse events	Incidence of adverse events and serious adverse events at 3 and 6 months from hospital discharge.	Month 3, 6
Other	Incidence of Cardiovascular-related Composite Rehospitalization and Death	Composite number of cardiovascular-related rehospitalizations and death at 3 and 6 months from hospital discharge.	Month 3, 6
Other	Proteomics analysis	Two 5ml tubes of blood were drawn at baseline and at 6 weeks, and a centrifuge was used to separate serum, plasma, and blood cells for mechanistic exploration.	Baseline and Week 6
Primary	Score of Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ)	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a self-administered, 23-item questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. All scores are represented on a 0-to-100-point scale, where lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life.	Baseline and Week 6
Primary	Maximal Inspiratory Pressure as a Percentage of Predicted Value (PImax%pred)	Participants will tries their best to exhale to the residual position, and then inhale as much as possible for 2~3 seconds to measure PImax and the percentage of PImax%pred	Baseline and Week 6
Secondary	Score of Short Physical Performance Battery (SPPB)	The SPPB measures physical function using 3 components: standing balance with progressively narrow base of support, usual gait speed over 4 meters, and time to complete 5 chair rises. The total score ranges from 0 to 12, with higher scores indicating better physical function.	Baseline and Week 6
Secondary	Score of Frailty	Patients were classified as frail if they met three or more of the following criteria: weak grip strength, physical exhaustion, slowness, low physical activity and unintentional weight loss.	Baseline and Week 6
Secondary	Pulmonary Function	Measurements of forced vital capacity and forced expiratory volume in 1 s were obtained with a computerized spirometer.	Baseline and Week 6
Secondary	Rate of All-Cause Rehospitalization	Number of all-cause rehospitalizations 6 months from hospital discharge.	Month 6