Heart Failure
Conditions
Keywords
advanced or end-stage heart failure, radiotherapy
Brief summary
The RADIATE-HF study is a prospective, interventional, single-center, open-label, non-randomized study conducted at the Rennes University Hospital. The goal of this proof-of-concept trial is to demonstrate that low-dose cardiac radiation therapy (5 Gy) improves left ventricular function by more than 5% in the medium term in patients with advanced or end-stage heart failure. The primary endpoint is the difference between the baseline value and the 6-month value of the LVEF as assessed by cardiac MRI. The study includes a single group of 20 patients receiving the intervention (cardiac radiation). The study is being conducted at a single investigator site.
Interventions
RADIATIONLow-dose cardiac radiation therapy (5 Gy)
Participants included in the RADIATE-HF study will receive a single-fraction cardiac radiotherapy treatment of 5 Gy, delivered by a linear accelerator (LINAC). This strategy aims to expose the ventricular myocardium (both ventricles) to a low, uniform dose, based on preclinical findings suggesting an anti-fibrotic and anti-remodelling effect. The procedure comprises three successive phases: 1. Pre-treatment assessments, 2. Planning and delivery of radiotherapy, 3. Post-treatment assessments.
Sponsors
Rennes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Low-dose cardiac radiation therapy (5 Gy)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Minimum age: 18 years 2. Ischaemic or non-ischaemic cardiomyopathies 3. Optimal medical treatment 4. LVEF ≤ 40% 5. NYHA class II or III 6. Life expectancy \> 6 months 7. At least one hospital admission for heart failure within the 6 months prior to inclusion, or NT-pro BNP ≥ 1,000 pg/mL 8. Contraindications to heart transplantation and left ventricular or biventricular assist devices 9. Having given their free and informed written consent 10. Covered by a health insurance scheme
Exclusion criteria
1. Pregnancy or breastfeeding 2. History of thoracic radiotherapy 3. History of aortic and mitral valve surgery 4. Contraindications to MRI (claustrophobia, presence of metallic foreign bodies) 5. Participation in another ongoing interventional study 6. Adults subject to legal protection measures (judicial protection, guardianship, curatorship), deprived of their liberty, or unable to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medium-term left ventricular function | 6 months [± 15 days] - complete-case analysis | Difference between the baseline value and the 6-month value of LVEF as assessed by cardiac MRI. Mean difference with 95% CI. Paired plot (spaghetti plot) of baseline values versus 6-month values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventricular dimensions and function, and the response in terms of myocardial structure and function on MRI | 6 months [± 15 days] - complete-case analysis: as the number of patients included in the study (n = 20) is limited, no multiple imputation will be performed; all assessments will be carried out on patients with complete data. | Difference between baseline and 6-month values, as assessed by cardiac MRI, of: * right ventricular ejection fraction * left ventricular end-diastolic volume * right ventricular end-diastolic volume * left ventricular end-systolic volume * right ventricular end-systolic volume * late enhancement * T1 and T2 mapping * extracellular volume. Difference in mean with 95% CI; paired plot (spaghetti plot) comparing baseline values with those at 6 months. |
| Ventricular dimensions and function, and the response in terms of myocardial structure and function on echocardiography | 6 months [± 15 days] - complete-case analysis: as the number of patients included in the study (n = 20) is limited, no multiple imputation will be performed; all assessments will be carried out on patients with complete data. | Difference between the baseline value and the value at 6 months, as assessed by echocardiography, of * the left ventricular ejection fraction * the global longitudinal strain, * myocardial work * left ventricular end-diastolic volume * left ventricular end-diastolic diameter * left ventricular end-systolic volume * cardiac output Difference in mean with 95% CI; paired plot (spaghetti plot) comparing baseline values with those at 6 months. |
| Serious complications related to the procedure | 6 months [± 15 days] - safety analysis set: the safety analysis population will include all patients who received single-fraction radiotherapy, regardless of completion or compliance with the protocol. | Percentage of patients experiencing at least one serious complication (6 months) related to radiotherapy. Severity is defined according to CTCAE v6 as grade 3 toxicity requiring hospitalisation or grade 4 or 5 toxicity. Percentage with 95% CI. Adverse events will also be presented using the MedDRA 'Preferred Terms' and their severity will be assessed according to the CTCAE \[\< 3 or ≥ 3\]. |
| Hospitalisation for cardiovascular reasons | 6 months [± 15 days] - complete-case analysis | Number of patients hospitalised for cardiovascular reasons (i.e. heart failure, arrhythmias) at 6 months. Percentage with 95% CI |
| Quality of life assessment | 6 months [± 15 days] - complete-case analysis | Difference between baseline and 6-month values for quality of life as assessed by the KCCQ, the Minnesota Living with Heart Failure Questionnaire, PGA and EQ-5D-5L. KCCQ: score from 0 to 100 Minnesota Living with Heart Failure Questionnaire: total score ranges from 0 to 105, with higher scores indicating a worse quality of life and greater impact from heart failure PGA: only one question EQ-5D-5L: Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems Mean difference with 95% CI. Paired plot (spaghetti plot) showing baseline values, values at 3 months and values at 6 months. |
| Survival | 6 months [± 15 days] - complete-case analysis | 6-month mortality rate. Restricted Mean Survival Time, Kaplan-Meier curve |
| Changes in biomarkers | 6 months [± 15 days] - complete-case analysis | Difference between baseline and 6-month values for NT-proBNP and troponin. Mean difference with 95% CI. Paired plot (spaghetti plot) showing baseline, 3-month and 6-month values. |
| Functional capacity during exercise | 6 months [± 15 days] - complete-case analysis | Difference between the baseline value and the 6-month value of the 6-minute walk test Difference in mean with 95% CI. Paired plot (spaghetti plot) showing the baseline value, the 3-month value and the 6-month value. |
Countries
France
Contacts
CONTACTGuillaume L'Official, MD
CONTACTRaphaël Martins, MD
Outcome results
None listed