Clinical trial NCT06694727: A Danish Pragmatic Randomized Trial of Nutritional Supplements in Heart Failure
Official title: A Danish Pragmatic Randomized Trial of Nutritional Supplements in Heart Failure (DANUTRIO-HF: Q10, DANUTRIO-HF: Selenium)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Heart Failure
Keywords: Heart failure
Coenzyme Q10
Selenium
Randomized Controlled Trial
Registry
Echocardiography
Pragmatic
Factorial
2x2
Cardiovascular
Nutritional supplements
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Pharma Nord
First posted: 2024-11-19
Enrollment: 4044
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Participants will be randomized in a 1:1 fashion to receive either the experimental intervention or placebo for each of the two nutritional supplements.
Primary purpose: TREATMENT

Brief summary: Heart failure is a common and serious condition. Despite rapid advancements in heart failure treatment, the prognosis remains severe. Smaller studies have shown that two simple, safe, and relatively inexpensive nutritional supplements-coenzyme Q10 and selenium-may reduce the risk of complications associated with heart failure. The DANUTRIO-HF trial will investigate whether these supplements can make a difference for individuals with heart failure. The study will assign approximately 4,044 patients from across Denmark to either coenzyme Q10 (100 mg twice daily) or a corresponding placebo, as well as selenium (100 μg twice daily) or its corresponding placebo, and follow how many of them end up being hospitalized for heart failure or dying from heart problems over an estimated two to three-year period.

Detailed description: This investigator-initiated, pragmatic, registry-based, double-blinded, placebo-controlled, 2x2 factorial, individually randomized trial aims to evaluate the efficacy of daily intake of the nutritional supplements coenzyme Q10 versus placebo, and selenium versus placebo, in preventing heart failure hospitalizations and cardiovascular death in heart failure patients. The trial plans to randomize approximately 4,044 participants in an event-driven design. Participants will be identified through the Danish Administrative Health Registries, which will also serve as the primary source for data collection. Contact with potential participants will be made via the mandatory Danish electronic letter system. No scheduled in-person visits are required in the main study, and all study interventions will be mailed to participants.

A substudy involving up to 600 participants will assess the effects of coenzyme Q10 and selenium on functional capacity, treatment compliance, biochemical biomarkers, and cardiac function and structure. This group will attend two in-person visits for additional evaluations, including echocardiography, blood sampling, and a 6-minute walk test at baseline and at the 1-year follow-up.

Eligibility criteria: Inclusion Criteria:

* Individuals aged ≥ 18 years.
* Registered with a heart failure diagnosis (ICD-10: I50) as a primary discharge diagnosis in The Danish National Patient Registry and at least one claimed prescription of a renin-angiotensin-system inhibitor and a β-blocker within 120 days after HF diagnosis.
* Informed consent form has been signed and dated.

Exclusion Criteria:

* Use of vitamin K-antagonist
* Registered with a cancer diagnosis (C00-C97 not C44) within the last 5 years excluding cutaneous squamous cell or basal cell carcinoma in The Danish National Patient Registry.

Primary outcomes:
measure: Time to the first occurrence of hospitalization for heart failure or cardiovascular death
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
Secondary outcomes:
measure: Time to first occurrence of hospitalization for heart failure
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to cardiovascular death
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
Other outcomes:
measure: Total number of hospitalizations for heart failure
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of hospitalizations for heart failure and cardiovascular death
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to the first occurrence of hospitalization for heart failure or all-cause death
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of hospitalizations for heart failure and all-cause death
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to all-cause mortality
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to first occurrence of major adverse cardiovascular events
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of major adverse cardiovascular events
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to first occurrence of hospitalization for any cardiovascular disease
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of hospitalizations for any cardiovascular disease
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to first occurrence of hospitalization for any cardiorespiratory disease
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of hospitalizations for any cardiorespiratory disease
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to first hospitalization for atrial fibrillation
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of hospitalizations for atrial fibrillation
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to first occurrence of hospitalization for cardiac arrest
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Time to first hospitalization for any cause
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Total number of hospitalizations for any cause
timeFrame: From date of randomization until end of study (Up to approximately 33 months)
measure: Change in Kansas City Cardiomyopathy Questionnaire Score
timeFrame: Aproximately within 1 year after randomization
measure: Change in left ventricular ejection fraction assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left ventricular global longitudinal strain assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in E/e'-ratio assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left ventricular mass assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in interventricular septal wall thickness assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left ventricular posterior thickness assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left atrial volume assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left atrial resevoir strain assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left atrial contraction strain assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in left atrial conduit strain assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in tricuspid annular plane systolic excursion assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in right ventricular free wall longitudinal strain assessed with echocardiography
timeFrame: Aproximately within 1 year after randomization
measure: Change in pro-BNP
timeFrame: Aproximately within 1 year after randomization
measure: Change in high sensitivity troponin-I
timeFrame: Aproximately within 1 year after randomization
measure: Change in hs-CRP
timeFrame: Aproximately within 1 year after randomization
measure: Concentration of coenzyme Q10 at followup
timeFrame: Aproximately within 1 year after randomization
measure: Concentration of selenoprotein P and selenium at followup
timeFrame: Aproximately within 1 year after randomization
measure: Change in 6 minute walking distance
timeFrame: Aproximately within 1 year after randomization
Locations:
city: Hellerup
country: Denmark
facility: Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
Study officials:
affiliation: Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
name: Tor Biering-Sørensen, MD, MPH, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References: