Propranolol for Congenital Heart Disease

Recruiting at 3 trial locations

Overseen By Rashida Blackwood, BS, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Propranolol interactions

Disqualifiers: Congenital AV block, Asthma, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2-8 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Propranolol, a medication, can increase the growth of heart muscle cells in infants with congenital heart disease, specifically those with Tetralogy of Fallot (a heart defect affecting normal blood flow). The aim is to determine if this drug can improve heart health by promoting new heart muscle cell growth. Eligible infants are those under 60 days old, have Tetralogy of Fallot, and weigh more than 2 kg. The trial includes two groups: one receiving Propranolol and the other a placebo, which contains no active ingredients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

Will I have to stop taking my current medications?

The trial requires that participants do not take medications that interact with propranolol. If you are on such medications, you may need to stop them to participate.

Is there any evidence suggesting that Propranolol is likely to be safe for humans?

Research has shown that propranolol, the treatment under study, is generally safe for infants and children. The FDA has already approved it to treat hemangioma, a type of non-cancerous tumor in infants, indicating its safety for young patients.

In past studies, propranolol treated heart problems in children, such as sudden drops in oxygen levels in infants with Tetralogy of Fallot, a congenital heart defect. This demonstrates its safe use in similar situations.

Although this study remains in the early stages, propranolol's existing use for other conditions in young patients provides some reassurance about its safety. However, monitoring for possible side effects remains important with any treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard approach for treating congenital heart disease, which often lacks a specific pharmacologic therapy for infants with Tetralogy of Fallot (ToF), propranolol offers a unique approach. Propranolol is a beta-blocker that may help manage symptoms by reducing the heart's workload and oxygen demand, potentially stabilizing the condition until surgery. Researchers are excited about propranolol because it targets the heart's beta-adrenergic receptors, which is different from the usual supportive care. This could mean a more effective management strategy for infants awaiting surgical repair, providing a valuable option where few currently exist.

What evidence suggests that Propranolol might be an effective treatment for congenital heart disease?

Research shows that propranolol, which participants in this trial may receive, might help individuals with Tetralogy of Fallot, a heart condition, by reducing the risk of sudden drops in blood oxygen levels. Studies also suggest that taking propranolol before heart surgery could lower the risk of developing junctional ectopic tachycardia (JET), a specific type of irregular heartbeat, afterward. Although propranolol is mainly approved for treating non-cancerous tumors in infants, there is interest in its potential to help heart muscle grow by encouraging the production of new heart muscle cells. This could be especially beneficial for patients with congenital heart disease, where heart muscle growth is often limited. While these findings are promising, further research is needed to fully understand how propranolol might help in this area. ^{2 3 4 6 7}

Who Is on the Research Team?

Bernhard Kuhn, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for male and female infants under 45 days old with specific heart conditions (Tetralogy of Fallot or double outlet right ventricle) who weigh over 2 kg and can tolerate feeding by mouth. It's not for babies born before 35 weeks, those with certain EKG results, on medications that affect propranolol, have diabetic mothers, respiratory issues, or metal implants.

Inclusion Criteria

My infant has a specific heart condition, is under 45 days old, weighs more than 2 kg, and can tolerate feeding.

My condition is diagnosed as DORV.

Exclusion Criteria

You are less than 35 weeks pregnant.

My child was born to a diabetic mother or has asthma or another respiratory condition.

My infant has a metal implant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Propranolol or placebo starting at 1 month of age until surgical repair, which occurs at 3-9 months of age

2-8 months

Regular monitoring visits as per protocol

Surgical Intervention

Surgical repair of Tetralogy of Fallot, during which heart muscle tissue is collected for analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Propranolol Hydrochloride

Trial Overview The study tests if Propranolol can help grow new heart muscle cells in infants with congenital heart disease. It involves a comparison between Propranolol and a placebo while monitoring through cardiac MRI, echocardiograms, urine collection, physical exams and specimen collection from surgery.

How Is the Trial Designed?

Group I: Propranolol Active Control 7 Interventions

The target dose of Propranolol hydrochloride for this study target dose for this study will be 4 mg/kg/day divided in 4 doses. The concentration of propranolol solution is 20 mg/5 mL. Additionally, labeled syringes will be provided to families for accurate weight-based dosing. Treatment with propranolol will begin at 1 month of age and continue until 4 months of age or 24hrs prior to surgical repair, whichever comes first.

Group II: Placebo Placebo Group 7 Interventions

Placebo will be given in a volume that corresponds to the patient's weight. Additionally, labeled syringes will be provided to families for accurate weight-based dosing. Treatment with placebo will begin at 1 month of age and continue until 4 months of age or 24hrs prior to surgical repair, whichever comes first. There is no current standard of care for pharmacologic therapy for infants with Tetralogy of Fallot (ToF). As such, there are no alternative treatments, and the placebo group is standard of care.

Propranolol Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in European Union as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in Canada as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Bernhard Kuhn

Lead Sponsor

Trials

1

Recruited

40+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In children with congenital heart disease, heart failure is prevalent in up to 20% of cases, necessitating effective medical therapy before or after surgery.

Propranolol has shown significant benefits in managing heart failure symptoms and improving heart function without serious side effects, making it a promising treatment option for infants with severe heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-Blockers in Children with Congenital Heart Disease Before a Corrective Procedure. Buchhorn, R.[2019]

Topical propranolol hydrochloride gel was found to be effective and safe for treating superficial infantile hemangiomas, with 44.83% of patients showing good improvement and 13.79% achieving excellent results based on a study of 51 cases.

The treatment demonstrated significantly better responses in superficial hemangiomas compared to other types, indicating its targeted efficacy, with no adverse effects reported during the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical propranolol hydrochloride gel for superficial infantile hemangiomas. Wang, L., Xia, Y., Zhai, Y., et al.[2021]

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

In a study of 22 infants with congestive heart failure due to pulmonary overcirculation, those treated with Propranolol showed significantly better clinical outcomes, including lower heart failure scores and shorter hospital stays compared to those treated with Captopril.

Propranolol also resulted in improved heart function, as indicated by lower left atrial and end-diastolic ventricular pressures, while Captopril did not effectively suppress angiotensin converting enzyme levels at the doses used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of low dose captopril versus propranolol therapy in infants with severe congestive failure due to left-to-right shunts. Buchhorn, R., Ross, RD., Hulpke-Wette, M., et al.[2019]

Propranolol hydrochloride is an effective treatment for infantile hemangiomas (IHs), showing significant reductions in volume, color, and elevation after 6 months of treatment in a study of 40 children aged 9 weeks to 5 years.

The treatment was safe, with no significant adverse effects like hypoglycemia or hypotension reported, and IH growth stopped within 4 weeks for those receiving propranolol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of propranolol for infantile hemangiomas. Hogeling, M., Adams, S., Wargon, O.[2022]

In a study of 70 patients with coronary heart disease (CHD) experiencing angina attacks, the combination of propranolol and syndnopharm therapy resulted in a positive clinical effect for 83.6% of patients.

The combination therapy also showed a positive change in ECG results for 64.2% of patients, suggesting enhanced efficacy, particularly for those who are intolerant to nitrates and do not have significant heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of combined administration of obsidan and sidnofarm in patients with ischemic heart disease at a polyclinic]. Borisov, AV.[2013]

In a study of 108 infants treated with oral propranolol for infantile hemangiomas, the medication was found to cause statistically significant but asymptomatic decreases in blood pressure and heart rate, indicating it is generally safe for use in this population.

No arrhythmias were detected during treatment, and while mild sleep disturbances were noted in some infants, overall heart rhythm and circadian patterns remained stable, suggesting that extensive monitoring may not be necessary for safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral propranolol for infantile hemangiomas: a prospective study on the role of 48-hour Holter monitoring in additional safety assessment. Petrovic, J., Trifunovic, B., Vukomanovic, G., et al.[2018]

The study analyzed data from the Canadian Adverse Drug Reaction Monitoring Program to assess the potential link between propranolol hydrochloride and bradycardia, finding that the signals for bradycardia were not statistically significant despite some high calculated statistics.

Although the results did not confirm a strong association between propranolol and bradycardia, the authors suggest that further investigation using larger databases is warranted due to the observed trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. Gavali, DK., Kulkarni, KS., Kumar, A., et al.[2021]

In a study of 198 hospitalized patients, 10% experienced adverse reactions to practolol, primarily affecting cardiac function, with some reactions being life-threatening.

Practolol and propranolol showed similar rates of cardiovascular complications, but practolol was also associated with skin reactions, indicating a broader range of potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to practolol in hospitalized patients: a report from the Boston Collaborative Drug Surveillance Program. Pfeifer, HJ., Greenblatt, DJ., Koch-Weser, J.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39017729/

Propranolol Therapy in Tetralogy of Fallot: Treating the ... Thirty-six (39%) patients received propranolol and 19% of patients developed hypercyanotic spells prior to surgery. Patients with higher peak ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1216539/

Propranolol treatment in children with tetralogy of Fallot ... Propranolol is given to prevent hypoxaemic episodes in children with tetralogy of Fallot who are awaiting operation it is advisable to continue the treatment ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04713657?term=AREA%5BConditionSearch%5D(Tetralogy%20of%20fallot%20OR%20%22ventricular%20septal%20defect%20with%20pulmonary%20stenosis%20or%20atresia,%20dextraposition%20of%20aorta,%20and%20hypertrophy%20of%20right%20ventricle%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=10

Beta-blocker Administration for Cardiomyocyte Division Propranolol is approved by the Food and Drug Administration (FDA) to treat a certain kind of benign tumor in infants (hemangioma), but it is not currently ...

4. researchgate.net researchgate.net/publication/5758479_Propranolol_A_new_indication_for_an_old_drug_in_preventing_postoperative_junctional_ectopic_tachycardia_after_surgical_repair_of_tetralogy_of_Fallot

Propranolol: A new indication for an old drug in preventing ... Our findings suggest that the preoperative use of propranolol may decrease the incidence of JET after full surgical repair of TOF. A prospective ...

5. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/s12887-025-05707-4

Impact of congenital heart disease on clinical outcomes of oral ... Oral propranolol therapy (OPT) is currently recognized as the first-line treatment for IH [2], achieving an efficacy rate exceeding 90% while ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40319231/

Impact of congenital heart disease on clinical outcomes ... However, there is a lack of studies indicating whether the congenital heart disease (CHD) makes a difference in oral propranolol therapy (OPT).

7. auctoresonline.org auctoresonline.org/article/clinical-pharmacology-of-propranolol-in-infants-and-children

Clinical Pharmacology of Propranolol in Infants and Children Propranolol is effective in treating hypoxemic spells in 80% of infants with teratology of Fallot and the effectiveness is greater with large doses of ...