NCT07885514

Brief Summary

This randomized clinical trial will test whether a multimodal anti-inflammatory program added to standard treatment improves the prognosis of patients with heart failure who have recently been hospitalized or visited the emergency department for worsening heart failure. The program combines two parts: a structured physical exercise plan and a Mediterranean diet plan, adapted to each patient. A total of 214 adults with heart failure and mildly reduced or preserved ejection fraction (LVEF 40% or higher), recent worsening of heart failure, and elevated inflammatory markers (C-reactive protein) will take part. Patients with frailty or malnutrition are excluded from the study. Patients will be recruited from heart failure clinics of participating Spanish hospitals. After agreeing to participate, patients will be randomly assigned to one of two groups: one group will continue their usual heart failure treatment, and the other will follow the same treatment plus the exercise and nutrition program delivered remotely by trained professionals for 12 months. The main question is whether the multimodal program reduces the combined occurrence of cardiovascular death, repeated heart failure hospitalizations, worsening exercise capacity (6-minute walk test), or worsening quality of life (Kansas City Cardiomyopathy Questionnaire) at 12 months. The study will also check whether the program lowers blood inflammatory and heart failure biomarkers (NT-proBNP, CA125), improves heart function on echocardiography, and whether patients' adherence to the program affects the results. All participants will continue to receive standard heart failure care; no medication is being tested, and the intervention consists of lifestyle coaching delivered by telephone or video calls.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
214

participants targeted

Target at P50-P75 for not_applicable heart-failure

Timeline
25mo left

Started Nov 2026

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 13, 2026

Completed
8 days until next milestone

First Posted

Study publicly available on registry

October 21, 2026

Completed
11 days until next milestone

Study Start

First participant enrolled

November 1, 2026

Expected
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2028

1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

October 21, 2026

Status Verified

October 1, 2026

Enrollment Period

2 years

First QC Date

October 13, 2026

Last Update Submit

October 13, 2026

Conditions

Heart FailureHeart Failure Preserved Ejection FractionHeart Failure, Diastolic (HFpEF)Chronic Inflammation

Keywords

Heart failureHFpEFInflammationExerciceMediterranean DietTelemonitoringWin ratioComposite endpoint

Outcome Measures

Primary Outcomes (1)

  • Hierarchical composite of cardiovascular death, recurrent heart failure hospitalizations, 6-minute walk test distance, and quality of life (KCCQ) at 12 months

    Hierarchical win ratio composite endpoint, ranked in descending order of clinical importance: 1) cardiovascular death; 2) recurrent HF hospitalizations (time to first and repeated events); 3) change from baseline in 6-minute walk test distance; 4) change from baseline in KCCQ score. Events adjudicated by a blinded independent Clinical Events Adjudication Committee. Comparison between arms by win ratio; analyzed by intention to treat.

    12 months

Secondary Outcomes (4)

  • All-cause mortality

    12 months

  • All-cause hospitalization

    12 months

  • Change in diastolic function (echocardiography)

    Baseline, 6 months, 12 months

  • Change in HF biomarkers

    Baseline, 6 months, 12 months

Other Outcomes (2)

  • Adherence to exercise and dietary interventions

    12 months

  • Predictive value of the INFLA score

    12 months

Study Arms (2)

Multimodal anti-inflammatory intervention (structured exercise + Mediterranean diet)

EXPERIMENTAL

Participants in this arm receive, in addition to standard heart failure management, a multimodal anti-inflammatory intervention for 12 months consisting of: (1) a structured, progressive physical exercise program prescribed and supervised by trained exercise professionals and (2) individualized Mediterranean diet counseling by trained nutrition professionals. Both components are delivered through remote/virtual visits with individualized recommendations and adherence monitoring. Contact begins within 10 days of randomization. Standard pharmacological treatment is maintained and managed by the treating heart failure team.

Behavioral: Structured exercise training programBehavioral: Mediterranean diet counseling

Standard heart failure management

ACTIVE COMPARATOR

Participants in this arm receive standard management at the heart failure unit of their participating center, including optimization of guideline-directed medical therapy and structured clinical follow-up, for 12 months. No lifestyle intervention components are added beyond usual care.

Other: Standard heart failure management

Interventions

Standard heart failure managementOTHER

Usual recommendations and guideline-directed management for heart failure at the participating center's HF unit (guideline-directed medical therapy and structured clinical follow-up) for 12 months. No lifestyle intervention added beyond standard care.

Standard heart failure management
Structured exercise training programBEHAVIORAL

Structured, progressive physical exercise program prescribed and supervised by trained exercise professionals. Delivered through remote/virtual visits with individualized recommendations and adherence monitoring, starting within 10 days of randomization and continuing for 12 months. Added to standard heart failure management.

Multimodal anti-inflammatory intervention (structured exercise + Mediterranean diet)
Mediterranean diet counselingBEHAVIORAL

Individualized Mediterranean diet counseling by trained nutrition professionals. Delivered through remote/virtual visits with adherence monitoring, for 12 months. Added to standard heart failure management.

Multimodal anti-inflammatory intervention (structured exercise + Mediterranean diet)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Basic ability to use electronic devices (smartphone, tablet or computer) and internet access.

You may not qualify if:

  • Concomitant disease with expected survival \<1 year.
  • Planned cardiac surgery within the next 3 months.
  • Implantable cardioverter-defibrillator with shocks delivered within the last 3 months.
  • Chronic use of systemic anti-inflammatory drugs or immunosuppressants.
  • Absolute contraindication to structured physical exercise, including: unstable angina; acute thromboembolism or embolic event within the last month; active endocarditis; acute myocarditis or pericarditis; acute aortic dissection or Marfan syndrome; acute systemic illness or fever; uncontrolled hypertension (resting SBP \>=160 mmHg and/or DBP \>=100 mmHg); uncontrolled tachyarrhythmia (resting heart rate \>120 bpm); third-degree atrioventricular block without pacemaker; hypertrophic cardiomyopathy with severe obstruction; progressive worsening of exercise tolerance or resting dyspnea in the last 3-5 days; significant ischemia (myocardial or lower-limb) at low workloads (\<2 METs or 50 W); poorly controlled diabetes mellitus, active proliferative retinopathy or moderate/worsening non-proliferative retinopathy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (8)

  • Pascual-Figal D, Nunez J, Perez-Martinez MT, Gonzalez-Juanatey JR, Taibo-Urquia M, Llacer-Iborra P, Delgado J, Villar S, Mirabet S, Aimo A, Riquelme-Perez A, Anguita-Sanchez M, Martinez-Selles M, Noguera-Velasco JA, Ibanez B, Bayes-Genis A. Colchicine in acutely decompensated heart failure: the COLICA trial. Eur Heart J. 2024 Dec 1;45(45):4826-4836. doi: 10.1093/eurheartj/ehae538.

    PMID: 39211951BACKGROUND

  • Everett BM, Cornel JH, Lainscak M, Anker SD, Abbate A, Thuren T, Libby P, Glynn RJ, Ridker PM. Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. Circulation. 2019 Mar 5;139(10):1289-1299. doi: 10.1161/CIRCULATIONAHA.118.038010.

    PMID: 30586730BACKGROUND

  • Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, Henderson AD, Lam CSP, Pitt B, Senni M, Shah SJ, Voors AA, Zannad F, Abidin IZ, Alcocer-Gamba MA, Atherton JJ, Bauersachs J, Chang-Sheng M, Chiang CE, Chioncel O, Chopra V, Comin-Colet J, Filippatos G, Fonseca C, Gajos G, Goland S, Goncalvesova E, Kang S, Katova T, Kosiborod MN, Latkovskis G, Lee AP, Linssen GCM, Llamas-Esperon G, Mareev V, Martinez FA, Melenovsky V, Merkely B, Nodari S, Petrie MC, Saldarriaga CI, Saraiva JFK, Sato N, Schou M, Sharma K, Troughton R, Udell JA, Ukkonen H, Vardeny O, Verma S, von Lewinski D, Voronkov L, Yilmaz MB, Zieroth S, Lay-Flurrie J, van Gameren I, Amarante F, Kolkhof P, Viswanathan P; FINEARTS-HF Committees and Investigators. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2024 Oct 24;391(16):1475-1485. doi: 10.1056/NEJMoa2407107. Epub 2024 Sep 1.

    PMID: 39225278BACKGROUND

  • McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

    PMID: 34447992BACKGROUND

  • Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Fito M, Gea A, Hernan MA, Martinez-Gonzalez MA; PREDIMED Study Investigators. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018 Jun 21;378(25):e34. doi: 10.1056/NEJMoa1800389. Epub 2018 Jun 13.

    PMID: 29897866BACKGROUND

  • Morley JE, Malmstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging. 2012 Jul;16(7):601-8. doi: 10.1007/s12603-012-0084-2.

    PMID: 22836700BACKGROUND

  • Leifer ES, Flynn KE, Keteyian SJ, Kitzman DW, Sachdev V. Supervised Exercise Training Improves Quality of Life in Chronic Heart Failure With Preserved Ejection Fraction: A META-ANALYSIS OF RANDOMIZED TRIALS. J Cardiopulm Rehabil Prev. 2025 Sep 1;45(5):364-370. doi: 10.1097/HCR.0000000000000972. Epub 2025 Aug 22.

    PMID: 40622851BACKGROUND

  • Angel Perez-Rivera J, Bonilla-Palomas JL, Diez-Villanueva P, Jimenez-Mendez C, Solla-Suarez P, Lopez-Azor JC, Ayala-Munoz R, Rodriguez-Santamarta M, Ortiz-Cortes C, Robles-Gamboa C, Enriquez-Rodriguez E, Taibo-Urquia M, Goirigolzarri-Artaza J, Morales-Martinez T, Alfonso F, Gonzalez-Gonzalez J, Esteban-Fernandez A. Nutritional intervention in older outpatients with chronic heart failure and malnutrition or at risk of malnutrition: the BOCADOS-IC randomized trial. Rev Esp Cardiol (Engl Ed). 2026 Jul 20:S1885-5857(26)00158-1. doi: 10.1016/j.rec.2026.07.001. Online ahead of print. English, Spanish.

    PMID: 42476223BACKGROUND

MeSH Terms

Conditions

Heart FailureHeart Failure, DiastolicHeart MurmursInflammation

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsPathologic Processes

Central Study Contacts

Alberto Esteban Fernández, Principal Investigator

CONTACT

+34 646101047aesteban@salud.madrid.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
Open-label trial: participants and treating clinicians are aware of treatment assignment. A blinded, independent Clinical Events Adjudication Committee (three cardiologists external to the study) adjudicates all clinical outcome events (cardiovascular death, recurrent heart failure hospitalizations) after reviewing source documentation. Centralized computer-generated randomization with concealed allocation; the assigned arm cannot be predicted or modified by investigators.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Two parallel arms with 1:1 allocation. Arm 1 (intervention): multimodal anti-inflammatory program - structured exercise training plus individualized Mediterranean diet counseling - delivered by trained exercise and nutrition professionals through remote/virtual visits for 12 months, added to standard heart failure management. Arm 2 (control): standard heart failure unit management alone. Centralized computer-generated randomization with concealed allocation; no stratification.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant Cardiologist

Study Record Dates

First Submitted

October 13, 2026

First Posted

October 21, 2026

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

December 1, 2028

Last Updated

October 21, 2026

Record last verified: 2026-10

Data Sharing

IPD Sharing
Will share

De-identified individual participant data underlying the published results will be shared: baseline demographics and clinical characteristics; randomized treatment assignment; primary and secondary outcome data (cardiovascular death, recurrent heart failure hospitalizations, 6-minute walk test distance, KCCQ scores); biomarker values (NT-proBNP, CA125, C-reactive protein, neutrophil-to-lymphocyte ratio); echocardiographic parameters; and adherence data to the exercise and dietary interventions. Data will be de-identified (no direct identifiers), provided with a data dictionary, and accompanied by the study protocol and statistical analysis plan. Data will be available from 12 to 36 months after publication of the primary results, to researchers providing a methodologically sound proposal approved by the coordinating center, under a data access agreement.

Shared Documents
STUDY PROTOCOL, ANALYTIC CODE
Time Frame
Beginning 12 months and ending 36 months after publication of the primary results of the trial.
Access Criteria
De-identified individual participant data will be available to any qualified researcher (academic investigators, regulatory agencies, and other researchers with a scientific interest) who provides a methodologically sound research proposal. Requests must be sent to the principal investigator (aesteban@salud.madrid.org) and will be reviewed and approved by the study coordinating center and the responsible party. Approved requesters will receive the de-identified datasets with a data dictionary, the study protocol, and the analytic code (Stata), under a signed data access agreement defining permitted use, data security requirements, and prohibition of re-identification attempts or redistribution.