Maternal Oxygen for Fetal Left Heart Hypoplasia

(P-RCT-MHO Trial)

Overseen By Donna Capps

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: Shaine Morris

Disqualifiers: Multiple gestations, Aneuploidy, Hypertension, others

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

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

Compensation: Varies

Number of Visits: 30

Duration: From enrollment to delivery

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if maternal hyperoxygenation is an effective treatment for fetal left heart hypoplasia versus room air (placebo). This will be determined by measuring how well a baby's heart valves and their surrounding tissue are growing and functioning. In addition the investigators will examine brain growth using fetal ultrasound and MRI, and MRI of the child's brain after they are born to determine if there is greater neonatal brain maturity or mothers receiving oxygen compared to fetuses of mothers not receiving oxygen. Of note, the trial was initially randomized. However, due to low sample size and hesitation about randomization, the trial was converted to an open label study, allowing families opting for oxygen therapy to be in the intervention arm.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have certain maternal conditions like moderate to severe hypertension requiring medication, you may not be eligible to participate.

What data supports the effectiveness of the treatment Oxygen, O2, Placebo Gas for fetal left heart hypoplasia?

Some studies suggest that maternal hyperoxygenation (increased oxygen levels for the mother) can increase blood flow to the fetal heart and may help with the growth of heart structures in fetuses with left heart hypoplasia. However, the effectiveness of this treatment is controversial, as other studies have shown no significant improvement in heart development and potential negative effects on brain development. ^{1 2 3 4 5}

Is maternal oxygen therapy safe for fetuses with left heart hypoplasia?

Research on maternal hyperoxygenation (extra oxygen given to the mother) suggests it is generally safe for fetuses, including those with heart issues like left heart hypoplasia. Studies have looked at its effects on fetal heart structures and found it can improve heart dimensions without major safety concerns. ^{1 4 5 6 7}

How is the treatment of maternal oxygen for fetal left heart hypoplasia different from other treatments?

Maternal oxygen therapy is unique because it involves the mother breathing extra oxygen to potentially help the baby's heart grow better before birth. Unlike other treatments that might involve surgery or medication, this approach is non-invasive and focuses on improving blood flow and heart development in the fetus by increasing oxygen levels. ^{1 2 4 5 8}

Research Team

Shaine A Morris, MD, MPH

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for pregnant women whose fetuses have a heart condition called left heart hypoplasia and are likely to need neonatal intervention. Eligible participants should have specific echocardiography findings but no growth restrictions, multiple gestations, severe fetal conditions, or maternal health issues that could affect the fetus's blood flow.

Inclusion Criteria

Transverse aortic arch or isthmus z-score less than 2.0.

Mothers carrying fetuses with small left sided structures likely needing neonatal intervention, defined as the following on fetal echocardiography:

Sum of aortic and mitral valve z-scores (standard deviation based on gestational age) less than -4.5

Exclusion Criteria

My unborn baby has a severe heart valve narrowing.

My unborn baby has a heart valve problem.

Abnormal fetal atrioventricular or ventriculoarterial relationships, including double inlet left ventricle, double outlet right ventricle, transposition of the great arteries

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Mothers receive continuous maternal hyperoxygenation (CMH) therapy with 4 LPM flow 40% FiO2 oxygen or room air for 24 hours/day

From enrollment to delivery

Regular echocardiography visits until delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including postnatal brain MRI and neurodevelopmental assessments

Up to 12 months post-birth

Postnatal MRI within 30 days of birth, neurodevelopmental assessments at 6 and 12 months

Treatment Details

Interventions

• Oxygen
• Placebo Gas

Trial Overview The study tests if breathing extra oxygen (hyperoxygenation) can help babies with underdeveloped hearts grow better before birth compared to regular air. It checks heart valve development and brain growth through ultrasounds and MRIs before and after birth. Initially randomized, it's now open label due to low participation.

Participant Groups

Group I: Oxygen Group Active Control 1 Intervention

The mothers will be asked to be on 4 liter of oxygen through nasal cannula up to 24 hours a day. The subjects will be blinded to their treatment.

Group II: Control Group Active Control 1 Intervention

These mothers will not undergo CMH therapy

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

Approved in United States as Oxygen for:

• General anesthesia
• Respiratory distress
• Cardiac arrest
• Hypoxia

Approved in European Union as Oxygen for:

• General anesthesia
• Respiratory distress
• Cardiac arrest
• Hypoxia

Approved in Canada as Oxygen for:

• General anesthesia
• Respiratory distress
• Cardiac arrest
• Hypoxia

Who Is Running the Clinical Trial?

Shaine Morris

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

Maternal hyperoxygenation (MH) therapy in fetuses with congenital heart disease (CHD) showed promising results, with 270 fetuses treated and evidence of increased size in hypoplastic cardiac structures and improved blood flow metrics, indicating potential therapeutic benefits.

No significant adverse events were reported during the therapy, suggesting that MH is a safe intervention; however, further randomized controlled trials are necessary to confirm its efficacy and outcomes for specific types of CHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature. Co-Vu, J., Lopez-Colon, D., Vyas, HV., et al.[2020]

References

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

Hypoplastic Left Heart Syndrome: Is There a Role for Fetal Therapy? [2022]

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

Maternal hyperoxygenation for the human fetus: should studies be curtailed? [2021]

3. England pubmed.ncbi.nlm.nih.gov

Maternal hyperoxygenation and foetal cardiac MRI in the assessment of the borderline left ventricle. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Pilot study of chronic maternal hyperoxygenation and effect on aortic and mitral valve annular dimensions in fetuses with left heart hypoplasia. [2017]

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

Impact of Maternal Hyperoxygenation on Myocardial Deformation and Loading Conditions in Fetuses with and without Left Heart Hypoplasia. [2022]

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

Chronic intermittent materno-fetal hyperoxygenation in late gestation may improve on hypoplastic cardiovascular structures associated with cardiac malformations in human fetuses. [2021]

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

Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Pulmonary Vasoreactivity to Materno-Fetal Hyperoxygenation Testing in Fetuses with Hypoplastic Left Heart. [2017]