Brief Summary
This study is a multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate whether an injectable form of Coenzyme I (also known as nicotinamide adenine dinucleotide, or NAD⁺) is safe and effective for treating children with cardiac dysfunction (weak heart pumping).
Who can join? We plan to enroll 180 children under 18 years of age who are hospitalized with cardiac dysfunction, meaning their heart's pumping ability (left ventricular ejection fraction, or LVEF) is below 55%. Children will be recruited from five hospitals in China. Children with certain serious conditions, such as end-stage heart failure, severe liver or kidney problems, known allergy to the study drug, or active participation in another drug trial, will not be eligible.
What will participants receive?
All children will receive standard heart failure care as recommended by current guidelines. In addition, they will be randomly assigned (like drawing lots) to one of three groups:
Placebo group - receives standard care plus a saltwater (normal saline) infusion that looks like the study drug but contains no active medicine (60 children).
Low-dose group - receives standard care plus Coenzyme I injection at 2 mg per kg of body weight per day (maximum 100 mg) (60 children).
High-dose group - receives standard care plus Coenzyme I injection at 4 mg per kg of body weight per day (maximum 200 mg) (60 children).
The study drug or placebo is given as a slow intravenous (IV) infusion once daily for 7 days. Each infusion takes at least 2 hours.
What is the main goal? The main question is whether adding Coenzyme I improves heart function more than standard care alone. The primary endpoint is the change in LVEF from baseline to 4 weeks after treatment, measured by echocardiography. We will also assess NT-proBNP, a blood test that reflects the strain on the heart, at several time points.
What else will we look at? We will also evaluate quality of life (using a child-friendly questionnaire), heart function grade (NYHA/ROSS), exercise capacity (6-minute walk test), growth and development, cardiac structure and remodeling (by echocardiography), global longitudinal strain (GLS), and clinical events such as heart failure-related rehospitalization, emergency interventions, and death. We will carefully monitor for any side effects or safety concerns throughout the study.
Why is this important? Children with cardiac dysfunction often do not respond well enough to current treatments, and there are few specific therapies designed for them. Coenzyme I (NAD⁺) is a natural substance in the body that helps heart cells produce energy. Studies in adults and in laboratory models suggest it may protect the heart and improve its function. This trial is the first large-scale pediatric study to test whether it can help children with heart pumping problems.
How long will participation last? Each child will be in the study for about 48 weeks - 7 days of treatment in the hospital, followed by follow-up visits at 4 weeks, 12 weeks, and 24 weeks after treatment, and a final telephone or clinic visit at 48 weeks to collect clinical event data.
Safety and oversight An independent Data and Safety Monitoring Board (DSMB) will regularly review all safety information. The study has been approved by the ethics committees of all participating hospitals and is conducted in accordance with the Declaration of Helsinki and Chinese Good Clinical Practice guidelines. All enrolled children are covered by clinical trial liability insurance.
Age < 18 years.
Hospitalized children diagnosed with cardiac dysfunction (LVEF < 55%).
Voluntary participation; written informed consent signed and dated by the legal guardian before enrollment in accordance with Good Clinical Practice (GCP) and local laws; assent from the age-appropriate child, if applicable.
Concomitant malignant arrhythmia; ischemic cardiomyopathy due to congenital or acquired coronary artery disease; cardiac dysfunction caused by systemic diseases (e.g., systemic lupus erythematosus, thyroid dysfunction).
End-stage/refractory heart failure: stage D heart failure with no improvement or worsening of symptoms and signs after adequate and standardized anti-heart-failure therapy (including but not limited to continuous intravenous infusion of positive inotropic agents such as dopamine, dobutamine, milrinone, or vasoactive agents).
Planned or prior advanced cardiac therapy: prior heart transplantation, or planned heart transplantation within 3 months after randomization, or implantation of a ventricular assist device (VAD, including LVAD/RVAD/BiVAD).
Known allergy to Coenzyme I; lactose intolerance or lactose allergy.
Parallel
Placebo
Other interventionIntravenous normal saline (0.9% sodium chloride), matching appearance and volume to the active drug. Administered once daily for 7 consecutive days. Each infusion is delivered over a minimum of 2 hours. Maximum volume is 125 mL per infusion.
Nicotinamide Adenine Dinucleotide
DrugPowder for injection, supplied as 5 mg/vial. Administered intravenously once daily for 7 consecutive days at a dose of either 2 mg/kg/day (maximum 100 mg) or 4 mg/kg/day (maximum 200 mg), diluted with normal saline to a concentration of 1.6 mg/mL. Each infusion is delivered over a minimum of 2 hours.
Change in Left Ventricular Ejection Fraction (LVEF) from Baseline to 4 Weeks
Change in LVEF from baseline to 4 weeks after treatment, assessed by echocardiography as a continuous variable. The primary analysis compares combined NAD⁺ groups (low-dose and high-dose) versus placebo using a one-sided difference test (δ₀ = 0) with ANCOVA, adjusting for baseline LVEF and center as a random effect (one-sided α = 0.025). Least-squares mean difference and 95% confidence interval will be estimated.
Change in N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) from Baseline
Change in NT-proBNP from baseline (continuous variable) at each follow-up visit. Assessed as the difference between post-treatment and baseline values.
Change in LVEF from Baseline at Multiple Time Points
Change in LVEF from baseline (continuous variable) at each follow-up visit, used to describe the recovery trajectory of LVEF over time.
Change in Left Ventricular End-Diastolic Diameter (LVEDD) from Baseline
Change in left ventricular end-diastolic diameter (LVEDD) from baseline, assessed by echocardiography. Units: millimeters (mm).
Change in Left Ventricular End-Systolic Diameter (LVESD) from Baseline
Change in left ventricular end-systolic diameter (LVESD) from baseline, assessed by echocardiography. Units: millimeters (mm).
Incidence of Adverse Events (AEs)
Incidence, severity, relationship to study drug, and outcome of adverse events (AEs). Unit: proportion/rate.
Incidence of Serious Adverse Events (SAEs)
Incidence, severity, relationship to study drug, and outcome of serious adverse events (SAEs). Unit: proportion/rate.
Exploratory Comparison of LVEF Change Between Low-Dose and High-Dose NAD⁺
Between-group difference in LVEF change from baseline at each follow-up visit, for hypothesis generation only. Units: percentage points (%).
Exploratory Comparison of NT-proBNP Change Between Low-Dose and High-Dose NAD⁺
Between-group difference in NT-proBNP change from baseline at each follow-up visit, for hypothesis generation only. Units: pg/mL (or pmol/L, as measured).
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