A Danish Pragmatic Randomized Trial of Nutritional Supplements in Heart Failure (DANUTRIO-HF)

A Danish Pragmatic Randomized Trial of Nutritional Supplements in Heart Failure (DANUTRIO-HF: Q10, DANUTRIO-HF: Selenium)

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Dietary supplement: Coenzyme Q10 100 Milligrams Oral Capsule; Dietary supplement: Selenium 100 Micrograms Oral Tablets

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.

• Study Type: Interventional
• Enrollment (Estimated): 4044
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kristoffer G Skaarup, MD; Phone Number: +4542451250; Email: kristoffer.grundtvig.skaarup@regionh.dk
• Study Contact Backup: Name: Tor Biering-Sørensen, MD, MPH, MSc, PhD; Phone Number: +4528933590; Email: tor.biering-soerensen@regionh.dk

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Recruiting
    • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
    • Contact: Sine H Christensen, MSc; Email: sine.hoejlund.christensen@regionh.dk
    • Contact: Kristoffer G Skaarup, MD; Phone Number: +4542451250; Email: kristoffer.grundtvig.skaarup@regionh.dk
    • Principal Investigator: Tor Biering-Sørensen, MD, MPH, MSc, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Coenzyme Q10 intervention, active; 100 mg capsules given twice daily, per oral use	Dietary supplement: Coenzyme Q10 100 Milligrams Oral Capsule; 100 mg capsules given twice daily, per oral use.
Placebo Comparator: Coenzyme Q10 intervention, placebo; Placebo matching coenzyme Q10	Dietary supplement: Coenzyme Q10 100 Milligrams Oral Capsule; 100 mg capsules given twice daily, per oral use.
Experimental: Selenium intervention, active; 100 μg tables given twice daily, per oral use	Dietary supplement: Selenium 100 Micrograms Oral Tablets; 100 μg tablets given twice daily, per oral use.
Placebo Comparator: Selenium intervention, placebo; 100 μg tables given twice daily, per oral use	Dietary supplement: Selenium 100 Micrograms Oral Tablets; 100 μg tablets given twice daily, per oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to the first occurrence of hospitalization for heart failure or cardiovascular death	From date of randomization until end of study (Up to approximately 33 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to first occurrence of hospitalization for heart failure	From date of randomization until end of study (Up to approximately 33 months)
Time to cardiovascular death	From date of randomization until end of study (Up to approximately 33 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of hospitalizations for heart failure		From date of randomization until end of study (Up to approximately 33 months)
Total number of hospitalizations for heart failure and cardiovascular death		From date of randomization until end of study (Up to approximately 33 months)
Time to the first occurrence of hospitalization for heart failure or all-cause death		From date of randomization until end of study (Up to approximately 33 months)
Total number of hospitalizations for heart failure and all-cause death		From date of randomization until end of study (Up to approximately 33 months)
Time to all-cause mortality		From date of randomization until end of study (Up to approximately 33 months)
Time to first occurrence of major adverse cardiovascular events		From date of randomization until end of study (Up to approximately 33 months)
Total number of major adverse cardiovascular events		From date of randomization until end of study (Up to approximately 33 months)
Time to first occurrence of hospitalization for any cardiovascular disease		From date of randomization until end of study (Up to approximately 33 months)
Total number of hospitalizations for any cardiovascular disease		From date of randomization until end of study (Up to approximately 33 months)
Time to first occurrence of hospitalization for any cardiorespiratory disease		From date of randomization until end of study (Up to approximately 33 months)
Total number of hospitalizations for any cardiorespiratory disease		From date of randomization until end of study (Up to approximately 33 months)
Time to first hospitalization for atrial fibrillation		From date of randomization until end of study (Up to approximately 33 months)
Total number of hospitalizations for atrial fibrillation		From date of randomization until end of study (Up to approximately 33 months)
Time to first occurrence of hospitalization for cardiac arrest		From date of randomization until end of study (Up to approximately 33 months)
Time to first hospitalization for any cause		From date of randomization until end of study (Up to approximately 33 months)
Total number of hospitalizations for any cause		From date of randomization until end of study (Up to approximately 33 months)
Change in Kansas City Cardiomyopathy Questionnaire Score		Aproximately within 1 year after randomization
Change in left ventricular ejection fraction assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left ventricular global longitudinal strain assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in E/e'-ratio assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left ventricular mass assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in interventricular septal wall thickness assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left ventricular posterior thickness assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left atrial volume assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left atrial resevoir strain assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left atrial contraction strain assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in left atrial conduit strain assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in tricuspid annular plane systolic excursion assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in right ventricular free wall longitudinal strain assessed with echocardiography	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in pro-BNP	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in high sensitivity troponin-I	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in hs-CRP	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Concentration of coenzyme Q10 at followup	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Concentration of selenoprotein P and selenium at followup	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization
Change in 6 minute walking distance	In up to 600 participants in a planned substudy with two physical visits. One shortly after randomization and another 1 year after	Aproximately within 1 year after randomization

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Collaborators: Pharma Nord
• Investigators: Principal Investigator: Tor Biering-Sørensen, MD, MPH, MSc, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Randomized Controlled Trial; Cardiovascular; Registry; Echocardiography; Nutritional supplements; Coenzyme Q10; Selenium; Pragmatic; Factorial; 2x2
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Trace Elements; Micronutrients; Antioxidants; Protective Agents; Vitamins; Ubiquinone; Coenzyme Q10; Selenium
• Other Study ID Numbers: DANUTRIO-HF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Most data will be collected from Danish administrative health registries, which are subject to Danish legislation and can only be made available to a third party under certain conditions. Please contact the sponsor-investigator in case of any inquiries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No