Digoxin for Single Ventricle Heart

(Digoxin R01 Trial)

Recruiting at 1 trial location

Overseen By Alex Hammett, BS/BA

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Duke University

Must be taking: Digoxin

Disqualifiers: Prematurity, High creatinine, Heart block, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 180 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how digoxin, a common heart medication, is processed in infants with single ventricle heart disease and how it affects their heart function. Researchers will collect blood samples and medical record information while infants receive their regular care. The trial will not alter the current treatment plan or medications. Eligible infants have single ventricle heart disease, have undergone their first stage of heart surgery, and are under six months old.

As a Phase 1, Phase 2 trial, this research focuses on understanding how digoxin works in infants and measuring its effectiveness in a smaller group. This study offers a unique opportunity to contribute to medical knowledge and potentially improve future treatments.

Will I have to stop taking my current medications?

The study will not change your treatment plan or medications, so you can continue taking your current medications.

Is there any evidence suggesting that digoxin is likely to be safe for infants with single ventricle heart disease?

Research has shown that digoxin is often used for babies with a specific heart condition called single ventricle heart disease. It is associated with lower death rates during the critical period between surgeries. Past patients have demonstrated that digoxin is generally safe when used correctly for this condition. Studies have examined how well babies tolerate the medication and found it manageable in most cases. While there are some risks, the use of digoxin in these situations is well-documented, and its safety is considered acceptable for babies with this heart condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using digoxin for single ventricle heart conditions because it employs a tailored dosing strategy based on a population-specific pharmacokinetic model. Unlike standard treatments, which often use fixed dosing, this approach personalizes dosing according to a patient's weight, age, and kidney function. This customization aims to optimize effectiveness and minimize side effects, potentially improving outcomes for patients with this complex heart condition.

What is the effectiveness track record for digoxin in treating single ventricle heart disease?

Research has shown that digoxin can save the lives of infants with single ventricle heart disease. Studies have found that this medication improves survival during the critical period between surgeries for these heart conditions. In this trial, participants will receive digoxin dosing based on a population-specific pharmacokinetic model. Digoxin is often used in children's heart care and has shown promising results in aiding these young patients. This treatment may enhance heart function and increase survival rates during a vulnerable time for infants with this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Christoph Hornik, MD

Principal Investigator

Duke Clinical Research Institute

Are You a Good Fit for This Trial?

This clinical trial is for infants with a heart condition known as single ventricle heart disease. To participate, they must already be receiving routine care in a pediatric cardiac intensive care unit.

Inclusion Criteria

I am under 6 months old.

I've had the first stage of heart surgery but not the second.

My child is 30 days old or younger and needs the first stage of a heart operation.

Exclusion Criteria

Prematurity (gestational age <37 weeks) at birth

Serum creatinine > 2 mg/dL at enrollment

I have a slow heartbeat that needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive population-specific PK model-derived digoxin dosing

Up to 180 days

Regular visits for PK and PD sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Digoxin

Trial Overview The study is examining how the drug Digoxin, commonly given to infants with heart disease, is processed by their bodies and its effects on their heart function. Blood samples will be taken during regular care to analyze this.

How Is the Trial Designed?

Group I: Population specific PK model-derived digoxin dosing Experimental Treatment 1 Intervention

Digoxin elixir will be used to dose enterally every 12 hours. The dosage will be determined by the protocol PK model. Dosing is to be administered based on weight, postnatal age, and estimated glomerular filtration rate The duration of the participation could be up to 180 days. Day 1 to S2P or Day 180 (+/- 7)

Digoxin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Approved in United States as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Approved in Canada as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Approved in Japan as Lanoxin for:

• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Congestive heart failure

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Center for Child Health and Development (NICHD)

Collaborator

Trials

1

Recruited

20+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Duke Clinical Research Institute

Collaborator

Trials

69

Recruited

242,000+

Published Research Related to This Trial

Digitalis, particularly through intravenous administration, can significantly improve heart function in patients with chronic heart failure, increasing cardiac index and reducing heart rate, with these benefits lasting into long-term oral therapy.

Adding digoxin to standard treatments like vasodilators and diuretics provides additional clinical benefits for patients with moderate to severe heart failure symptoms due to systolic ventricular dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A reexamination of the hemodynamic effects of digitalis relative to ventricular dysfunction. Vitarelli, A., Fedele, F., Dagianti, A., et al.[2018]

Digoxin is effective for controlling ventricular rates in patients with atrial fibrillation, but its role in heart failure patients is unclear due to limited and small-scale studies that show inconsistent benefits.

Due to its narrow therapeutic range and potential for serious side effects, including increased mortality risk after myocardial infarction, digoxin should be used cautiously and is recommended as a third-line therapy behind safer options like ACE inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure: to digitalise or not? The view against. White, HD.[2019]

In a substudy of the DIG trial involving 589 patients with heart failure, digoxin therapy did not significantly improve health-related quality of life (HQOL) compared to placebo over 12 months.

While there was a slight improvement in perceived health at 4 months for the digoxin group, this benefit did not persist, and no significant differences were observed in various HQOL measures at the 12-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of digoxin on the quality of life in patients with heart failure. Lader, E., Egan, D., Hunsberger, S., et al.[2015]

Digoxin remains effective for treating patients with congestive heart failure (CHF) who also have atrial fibrillation, but it does not reduce mortality rates, as shown in large randomized trials.

The use of digoxin should be personalized, as it may benefit some patients with CHF due to systolic dysfunction but is not effective for those with diastolic dysfunction or certain congenital heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does digoxin still have a role in congestive heart failure? Kothari, SS.[2019]

Recent double-blind, randomized trials show that digoxin improves left ventricular ejection fraction, increases exercise capacity, and prevents worsening of congestive heart failure (CHF) compared to placebo, indicating its efficacy in treatment.

While digoxin provides benefits similar to ACE inhibitors in improving heart function, it does not improve survival rates, and its effects on mortality in CHF patients are still being studied in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of randomized trials of digoxin therapy in patients with chronic heart failure. Gheorghiade, M., Zarowitz, BJ.[2019]

Digoxin has been historically used to treat heart failure (HF) and can reduce hospital admissions for worsening HF in patients with sinus rhythm and ejection fraction <45%, but definitive evidence of its efficacy as an add-on therapy is lacking due to the emergence of newer heart failure treatments.

Current data on digoxin's safety and effectiveness in heart failure are primarily from observational studies, which show conflicting results, and there are concerns that digoxin may be harmful to some patients, highlighting the need for further research on optimal dosing and patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is foxglove effective in heart failure? Chaggar, PS., Shaw, SM., Williams, SG.[2015]

Digoxin is effective for controlling ventricular rate in patients with chronic atrial fibrillation, especially when combined with beta-blockers or calcium channel antagonists, but is less effective as a standalone treatment during exercise.

While digoxin is generally considered safe for patients with atrial fibrillation, its safety profile may not be fully understood due to limited studies, particularly in patients with heart failure, and potential adverse effects like cardiac arrhythmias should be monitored closely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of digoxin as a pharmacological treatment of atrial fibrillation. Tamargo, J., Delpón, E., Caballero, R.[2019]

Digoxin can be beneficial in managing heart failure by reducing hospital admissions for worsening symptoms, especially when added to standard treatments like ACE inhibitors and diuretics.

In elderly patients with atrial fibrillation, digoxin can help control heart rate but should be used cautiously due to the risk of toxicity; combining it with other medications may be safer than increasing the digoxin dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When, and when not, to use digoxin in the elderly. Gosselink, AT., van Veldhuisen, DJ., Crijns, HJ.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4859374/

Association of Digoxin With Interstage Mortality Digoxin use in infants with single ventricle congenital heart disease is associated with significantly reduced interstage mortality.

2. ajconline.org ajconline.org/article/S0002-9149(21)00527-0/fulltext

Impact of Digoxin Use on Interstage Outcomes of Single ... Digoxin use is associated with reduced interstage mortality in patients with no history of arrhythmia after stage i palliation for single ventricle heart ...

3. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4135497

Abstract 4135497: Model-informed dosing ... Digoxin is commonly used in infants with single ventricle heart disease (SVD) and may decrease mortality in the interstage period.

4. muschealth.org muschealth.org/health-professionals/progressnotes/2024/winter/infant-surgery-survival

Common heart medication digoxin shows promise in ... Treating certain single-ventricle patients with digoxin during a critical stage may enhance their survival and lead to better outcomes.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03877965

Pharmacokinetics and Safety Profile of Digoxin in Infants ... The secondary objective is to determine the safety profile of enteral digoxin in infants with single ventricle congenital heart disease. Digoxin is used for the ...

6. pediatrictrials.org pediatrictrials.org/digoxin/

Pharmacokinetics and Safety Profile of Digoxin in Infants ... This study aims to enroll up to 48 infants diagnosed with single ventricle CHD, receiving digoxin per standard of care during the interstage period.