Heart FailureFLARE-HFNCT07885514
Exercise, Mediterranean Diet and Inflammation in Heart Failure
A study testing Structured exercise training program, Mediterranean diet counseling and Standard heart failure management in people with Heart Failure and Heart Failure Preserved Ejection Fraction, run by Hospital Severo Ochoa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Heart Failure Preserved Ejection Fraction, Heart Failure, Diastolic (HFpEF)
- What is being tested?
- Structured exercise training program, Mediterranean diet counseling and Standard heart failure management
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Heart failure with left ventricular ejection fraction (LVEF) >=40%, diagnosed according to current clinical guidelines; LVEF measured by echocardiogram within the 3 months before inclusion. If LVEF >=50%, evidence of structural heart disease is required (at least one of: left atrial area >=4 cm2/m2, left atrial volume >30 mL/m2, or indexed left ventricular mass).
- At least one episode of heart failure decompensation within the 4 weeks before inclusion, defined as: hospitalization for HF, emergency department visit requiring intravenous diuretics (ED or HF day unit), and/or intensification of oral treatment after such a visit, and/or worsening HF signs/symptoms during outpatient follow-up.
- NT-proBNP >=300 pg/mL in sinus rhythm or >=900 pg/mL in atrial fibrillation (permanent or persistent), measured within the last month before inclusion.
- NYHA functional class I-III at inclusion.
- Systemic inflammation at inclusion, defined as C-reactive protein >=2 mg/L and neutrophil-to-lymphocyte ratio (NLR) >=3 (NLR = total neutrophil count / total lymphocyte count).
- Basic ability to use electronic devices (smartphone, tablet or computer) and internet access.
Who cannot join
- Frailty (FRAIL scale >=3) at inclusion.
- Malnutrition (MNA-SF <7) at inclusion.
- Concomitant disease with expected survival <1 year.
- Planned cardiac surgery within the next 3 months.
- Severe valvular heart disease (stenosis or regurgitation) at inclusion.
- Acute decompensated heart failure at inclusion (worsening signs/symptoms requiring intravenous diuretics and/or treatment intensification at the time of inclusion).
Show all 9Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effects of Multimodal Approach to Inflammation Versus Standard Treatment on the Prognosis of Patients With Heart Failure and Mildly Reduced or Preserved Ejection Fraction After Decompensation: FLARE-HF Randomized Trial.
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.
Read the detailed description
Background: Low-grade inflammation is a key pathophysiologic mechanism in heart failure (HF), particularly in the mildly reduced or preserved ejection fraction phenotype after decompensation. Available anti-inflammatory strategies show heterogeneous evidence of clinical benefit.
Objective: To determine whether a multimodal anti-inflammatory intervention (structured exercise plus Mediterranean diet) reduces a hierarchical composite endpoint at 12 months compared with standard treatment in patients with HF and LVEF ≥40% after a recent decompensation. Secondary objectives: effect on individual events (CV death, all-cause mortality, HF decompensation, all-cause hospitalization); on biomarkers (NT-proBNP, CA125) and diastolic function (echocardiography) at 6 and 12 months; on the primary endpoint by adherence levels; and on the predictive value of the INFLA score.
Design: Multicenter, pragmatic, randomized, controlled, superiority trial (parallel assignment, 1:1).
Population: Adults with HF and LVEF ≥40%, at least one HF decompensation within the previous 4 weeks, NT-proBNP ≥300 pg/mL in sinus rhythm (≥900 pg/mL in atrial fibrillation), NYHA class I-III, systemic inflammation (CRP ≥2 mg/L and neutrophil-to-lymphocyte ratio ≥3), and frailty (FRAIL ≥3) or malnutrition (MNA-SF <7).Sample size: 214 patients (107 per arm), allowing for 10% losses.Intervention: The experimental arm receives a structured exercise program and individualized Mediterranean diet counseling delivered by trained professionals through remote (virtual) visits during 12 months. The control arm receives standard HF management. Randomization after informed consent at HF clinic visits.
Outcomes: Primary outcome is a hierarchical composite (win ratio) at 12 months, ranked as follows: 1) cardiovascular death, 2) recurrent HF hospitalizations, 3) change in 6-minute walk test distance, 4) change in KCCQ score. Secondary outcomes: time to all-cause death or hospitalization, echocardiographic diastolic function parameters, NT-proBNP and CA125 levels at 6 and 12 months, adherence to exercise and dietary interventions, predictive value of the INFLA score.
Event adjudication: All primary, secondary and tertiary events will be adjudicated by an independent, blinded Clinical Events Adjudication Committee.
Timeline: Recruitment 12 months; follow-up 12 months; database closure and analysis thereafter. Results expected after study completion.
- Conditions
- Heart Failure, Heart Failure Preserved Ejection Fraction, Heart Failure, Diastolic (HFpEF), Chronic Inflammation
- Being tested
- Structured exercise training program, Mediterranean diet counseling, Standard heart failure management
- Keywords
- Heart failure, HFpEF, Inflammation, Exercice, Mediterranean Diet, Telemonitoring, Win ratio, Composite endpoint
- Medical subject headings
- Heart Failure, Heart Failure, Diastolic, Heart Murmurs, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Structured exercise training programBehavioural
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.
Mediterranean diet counselingBehavioural
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Behavioral: Structured exercise training program; Behavioral: 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. Receives: Other: Standard heart failure management |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (4)
All-cause mortality
Time to all-cause death compared between arms.
Measured: 12 months
All-cause hospitalization
Time to all-cause hospitalization compared between arms.
Measured: 12 months
Change in diastolic function (echocardiography)
Change from baseline in echocardiographic parameters of diastolic function at 6 and 12 months.
Measured: Baseline, 6 months, 12 months
Change in HF biomarkers
Change from baseline in NT-proBNP and CA125 serum levels.
Measured: Baseline, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Severo Ochoa
- Sponsor type
- University, hospital or other
- Collaborators
- Alfonso X El Sabio University, Camilo Jose Cela University
- Responsible party
- Principal investigator, Alberto Esteban Fernández, Hospital Severo Ochoa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07885514
- Sponsor's protocol ID
- FLARE-HF-2026
- Other IDs
- SEC/FEC-INV-CLI 26-43
- Acronym
- FLARE-HF
- Status last verified
- Oct 2026
- First submitted
- 13 Oct 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39211951Everett 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.
PubMed 30586730Solomon 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.
PubMed 39225278McDonagh 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.
PubMed 34447992Estruch 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.
PubMed 29897866Morley 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.
PubMed 22836700Leifer 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.
PubMed 40622851Angel 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.
PubMed 42476223
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Multimodal Approach to Inflammation Versus Standard Treatment on the Prognosis of Patients With Heart Failure and Mildly Reduced or Preserved Ejection Fraction After Decompensation: FLARE-HF Randomized Trial.
- ClinicalTrials.gov ID
- NCT07885514
- Acronym / sponsor ID
- FLARE-HF / FLARE-HF-2026
- Conditions
- Heart Failure, Heart Failure Preserved Ejection Fraction, Heart Failure, Diastolic (HFpEF), Chronic Inflammation
- Keywords
- Heart failure, HFpEF, Inflammation, Exercice, Mediterranean Diet, Telemonitoring, Win ratio, Composite endpoint
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Hospital Severo OchoaUniversity, hospital or other
- Collaborators
- Alfonso X El Sabio University, Camilo Jose Cela University
- Study start
- Nov 2026 (estimated)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 21 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background: Low-grade inflammation is a key pathophysiologic mechanism in heart failure (HF), particularly in the mildly reduced or preserved ejection fraction phenotype after decompensation. Available anti-inflammatory strategies show heterogeneous evidence of clinical benefit.
Objective: To determine whether a multimodal anti-inflammatory intervention (structured exercise plus Mediterranean diet) reduces a hierarchical composite endpoint at 12 months compared with standard treatment in patients with HF and LVEF ≥40% after a recent decompensation. Secondary objectives: effect on individual events (CV death, all-cause mortality, HF decompensation, all-cause hospitalization); on biomarkers (NT-proBNP, CA125) and diastolic function (echocardiography) at 6 and 12 months; on the primary endpoint by adherence levels; and on the predictive value of the INFLA score.
Design: Multicenter, pragmatic, randomized, controlled, superiority trial (parallel assignment, 1:1).
Population: Adults with HF and LVEF ≥40%, at least one HF decompensation within the previous 4 weeks, NT-proBNP ≥300 pg/mL in sinus rhythm (≥900 pg/mL in atrial fibrillation), NYHA class I-III, systemic inflammation (CRP ≥2 mg/L and neutrophil-to-lymphocyte ratio ≥3), and frailty (FRAIL ≥3) or malnutrition (MNA-SF <7).Sample size: 214 patients (107 per arm), allowing for 10% losses.Intervention: The experimental arm receives a structured exercise program and individualized Mediterranean diet counseling delivered by trained professionals through remote (virtual) visits during 12 months. The control arm receives standard HF management. Randomization after informed consent at HF clinic visits.
Outcomes: Primary outcome is a hierarchical composite (win ratio) at 12 months, ranked as follows: 1) cardiovascular death, 2) recurrent HF hospitalizations, 3) change in 6-minute walk test distance, 4) change in KCCQ score. Secondary outcomes: time to all-cause death or hospitalization, echocardiographic diastolic function parameters, NT-proBNP and CA125 levels at 6 and 12 months, adherence to exercise and dietary interventions, predictive value of the INFLA score.
Event adjudication: All primary, secondary and tertiary events will be adjudicated by an independent, blinded Clinical Events Adjudication Committee.
Timeline: Recruitment 12 months; follow-up 12 months; database closure and analysis thereafter. Results expected after study completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Multimodal anti-inflammatory intervention (structured exercise + Mediterranean diet) | Experimental | Behavioral: Structured exercise training program, Behavioral: Mediterranean diet counselingParticipants 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. |
| Standard heart failure management | Active comparator | Other: Standard heart failure managementParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Heart failure with left ventricular ejection fraction (LVEF) >=40%, diagnosed according to current clinical guidelines; LVEF measured by echocardiogram within the 3 months before inclusion. If LVEF >=50%, evidence of structural heart disease is required (at least one of: left atrial area >=4 cm2/m2, left atrial volume >30 mL/m2, or indexed left ventricular mass).
- At least one episode of heart failure decompensation within the 4 weeks before inclusion, defined as: hospitalization for HF, emergency department visit requiring intravenous diuretics (ED or HF day unit), and/or intensification of oral treatment after such a visit, and/or worsening HF signs/symptoms during outpatient follow-up.
- NT-proBNP >=300 pg/mL in sinus rhythm or >=900 pg/mL in atrial fibrillation (permanent or persistent), measured within the last month before inclusion.
- NYHA functional class I-III at inclusion.
- Systemic inflammation at inclusion, defined as C-reactive protein >=2 mg/L and neutrophil-to-lymphocyte ratio (NLR) >=3 (NLR = total neutrophil count / total lymphocyte count).
Key exclusion criteria (9 listed)
- Frailty (FRAIL scale >=3) at inclusion.
- Malnutrition (MNA-SF <7) at inclusion.
- Concomitant disease with expected survival <1 year.
- Planned cardiac surgery within the next 3 months.
- Severe valvular heart disease (stenosis or regurgitation) at inclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Structured exercise training programStructured, 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. | Behavioural | Multimodal anti-inflammatory intervention (structured exercise + Mediterranean diet) |
| Mediterranean diet counselingIndividualized Mediterranean diet counseling by trained nutrition professionals. Delivered through remote/virtual visits with adherence monitoring, for 12 months. Added to standard heart failure management. | Behavioural | Multimodal anti-inflammatory intervention (structured exercise + Mediterranean diet) |
| Standard heart failure managementUsual 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. | Other | Standard heart failure management |
Primary outcome
Hierarchical composite of cardiovascular death, recurrent heart failure hospitalizations, 6-minute walk test distance, and quality of life (KCCQ) at 12 months
Time frame: 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.
4 secondary outcomes
All-cause mortality
Time frame: 12 months
All-cause hospitalization
Time frame: 12 months
Change in diastolic function (echocardiography)
Time frame: Baseline, 6 months, 12 months
Change in HF biomarkers
Time frame: Baseline, 6 months, 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Background: PubMed 39211951Pascual-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.
- Background: PubMed 30586730Everett 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.
- Background: PubMed 39225278Solomon 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.
- Background: PubMed 34447992McDonagh 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.
- Background: PubMed 29897866Estruch 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.
- Background: PubMed 22836700Morley 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.
- Background: PubMed 40622851Leifer 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.
- Background: PubMed 42476223Angel 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.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Heart Failure
Not yet recruitingObservational study
Psychometric Evaluation of the Traditional Chinese Multidimensional Fatigue Inventory in Patients With Heart Failure
Heart Failure, Fatigue Severity Scale
RecruitingPhase 4
DECONGEST-AHF: Vasodilatation or Loop Diuretics in Acute Heart Failure
Pulmonary Edema, Congestive Heart Failure
Not yet recruitingPhase 3
A Clinical Study of Sotatercept (MK-7962) in People With Combined Postcapillary and Precapillary Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (MK-7962-041)
Pulmonary Hypertension
Not yet recruiting
Bedside Assessment of Right Ventricular Output Lying in Prone Or Supine
Right Ventricular Function, Prone Position
Recruiting
Mobile Health Intervention to Increase Activity in Heart Failure Study
Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing Structured exercise training program, Mediterranean diet counseling and Standard heart failure management in people with Heart Failure and Heart Failure Preserved Ejection Fraction, run by Hospital Severo Ochoa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alberto Esteban Fernández, Principal Investigator (+34 646101047, aesteban@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical composite of cardiovascular death, recurrent heart failure hospitalizations, 6-minute walk test distance, and quality of life (KCCQ) at 12 months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07885514, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.