Digoxin for Single Ventricle Heart

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?

The primary participant will be an infant with single ventricle heart disease. This is a research study to learn more about how the medication digoxin, which is routinely prescribed to infants and children with heart disease in pediatric cardiac intensive care units is processed by their bodies and how it may help their cardiac function. The investigators will collect blood or will collect blood samples when bloodwork is checked as part of regular care ("opportunistic"). The investigators will also collect information from medical records. Being part of this study will not change treatment plan or medications. The risks of this study include loss of confidentiality and risks associated with having blood drawn. The study team will make every effort to minimize these risks.

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 digoxin generally safe for human use?

Digoxin has been used for over 200 years and is generally considered safe, but it can cause heart rhythm problems and other side effects, especially in the elderly or when used with certain other medications. It has a narrow margin between effective and toxic doses, so careful monitoring is important. ^{1 2 3 4 5}

How is the drug digoxin unique in treating single ventricle heart conditions?

Digoxin is unique because it has been used for over 200 years to treat heart conditions by improving heart function and reducing hospital admissions for heart failure. It is the only oral inotropic agent (a drug that increases the strength of heart muscle contractions) currently used in clinical practice for heart failure, making it distinct from other treatments. ^{1 3 5 6 7}

What data supports the effectiveness of the drug Digoxin for heart conditions?

Research shows that Digoxin can improve symptoms and exercise capacity in patients with heart failure due to systolic dysfunction, and it is beneficial for controlling heart rate in patients with atrial fibrillation. However, its effect on mortality is unclear, and it should be used with caution. ^{2 4 5 6 8}

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 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 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 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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

A reexamination of the hemodynamic effects of digitalis relative to ventricular dysfunction. [2018]

2. India pubmed.ncbi.nlm.nih.gov

Does digoxin still have a role in congestive heart failure? [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Review of randomized trials of digoxin therapy in patients with chronic heart failure. [2019]

4. Australia pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

The effect of digoxin on the quality of life in patients with heart failure. [2015]

6. England pubmed.ncbi.nlm.nih.gov

The safety of digoxin as a pharmacological treatment of atrial fibrillation. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

When, and when not, to use digoxin in the elderly. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Is foxglove effective in heart failure? [2015]