An interventional study of Structured exercise training program and Mediterranean diet counseling in Heart Failure, Heart Failure Preserved Ejection Fraction and Heart Failure, Diastolic (HFpEF), sponsored by Hospital Severo Ochoa. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Hospital Severo Ochoa · Not applicable, Interventional, and Treatment
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.
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.
5,803 studies on the registry are indexed under Heart Failure; 1,222 are open to participants now.
This study's planned enrollment of 214 is above the median of 72 across 3,790 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Hospital Severo Ochoa is the lead sponsor of 6 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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 program · Behavioral: Mediterranean diet counseling
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
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.
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.
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.
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.
Time frame: 12 months
All-cause mortality
Time to all-cause death compared between arms.
Time frame: 12 months
All-cause hospitalization
Time to all-cause hospitalization compared between arms.
Time frame: 12 months
Change in diastolic function (echocardiography)
Change from baseline in echocardiographic parameters of diastolic function at 6 and 12 months.
Time frame: Baseline, 6 months, 12 months
Change in HF biomarkers
Change from baseline in NT-proBNP and CA125 serum levels.
Time frame: Baseline, 6 months, 12 months
Adherence to exercise and dietary interventions
Degree of adherence of participants in the intervention arm to the exercise program and the Mediterranean diet plan, and its impact on the primary endpoint.
Time frame: 12 months
Predictive value of the INFLA score
Value of the INFLA score to predict the composite of cardiovascular death and HF decompensation.
Time frame: 12 months
No study locations are listed for this record.
Documents are hosted by the registry — open the source record to download them.
Plan to share: 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.
Supporting information: 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.
Start is estimated for Nov 2026; primary completion for Nov 2028, 24 months later.
Of 1,018 non-industry interventional studies with no phase under Heart Failure, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 50. This study's planned 24 months is below that.
Counting every sponsor, half of 1,220 studies reached it within 31 months; a quarter within 16 and three quarters within 53.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Hospital Severo Ochoa