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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether providing extra oxygen to pregnant mothers can aid babies with a small left side of the heart. Researchers aim to determine if oxygen enhances the growth of these babies' heart valves and brains compared to those whose mothers breathe regular air. They will also assess the babies' brain development through various scans. This trial may suit mothers carrying a baby with small heart structures that might require treatment after birth. As an unphased trial, this study offers a unique opportunity for mothers to contribute to groundbreaking research that could improve outcomes for babies facing heart challenges.

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 prior data suggests that maternal hyperoxygenation is safe for fetal left heart hypoplasia?

Research has shown that using oxygen during pregnancy for babies with heart issues appears safe. One study found that providing a small, steady amount of oxygen was well-tolerated and safe for pregnant women with certain heart conditions. No major problems have been reported with this method. Oxygen is typically administered through a nasal tube, a common and easy method.

In simple terms, breathing extra oxygen during pregnancy hasn't raised any significant safety concerns, suggesting it is likely safe for both the mother and the baby. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using oxygen for fetal left heart hypoplasia because it offers a non-invasive approach that could enhance fetal heart development. Unlike standard treatments that often involve complex surgical interventions after birth, administering oxygen to expectant mothers is a simple and low-risk method. By potentially improving oxygen levels for the developing fetus, this treatment may support better heart growth and function even before birth, offering a new avenue of hope for managing this challenging condition.

What evidence suggests that maternal oxygen therapy might be an effective treatment for fetal left heart hypoplasia?

Research has shown that providing extra oxygen to pregnant mothers might enhance the development of a baby's left heart, particularly when the left side is underdeveloped. In this trial, some participants will receive oxygen therapy, which studies suggest could promote better heart growth and function. Additionally, there are indications that this therapy might aid brain development, potentially leading to more mature brain function in newborns. However, further research is necessary to confirm these potential benefits. Initial findings are promising, but evidence is still being collected. ^{1 6 7 8 9}

Who Is on the Research Team?

Shaine A Morris, MD, MPH

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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

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

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

Exclusion Criteria

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

Multiple gestations

Persistent fetal arrhythmia

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02965638

Trial of Maternal Oxygen for Fetal Left Heart Hypoplasia The purpose of this study is to determine if maternal hyperoxygenation is an effective treatment for fetal left heart hypoplasia versus room air (placebo).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9304816/

Hypoplastic Left Heart Syndrome: Is There a Role for Fetal ... Moreover, chronic MH may improve left heart development. Using chronic MH could show further benefits in fetuses after fetal aortic valvuloplasty. However, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6690741/

New Aspects in the Diagnosis and Therapy of Fetal ... Maternal hyperoxygenation (MH) therapy consists of providing supplemental oxygen to the mother during pregnancy to improve the cardiovascular ...

4. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.116.022816

Current Therapy for Hypoplastic Left Heart Syndrome and ... The Australia and New Zealand Fontan Registry, collating data from 1423 subjects, reported survival at 26 years of 89% for those operated on ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109711033420

Hypoplastic Left Heart Syndrome: Current Considerations ... The Society of Thoracic Surgeons Congenital Heart Surgery Database has shown an improvement in hospital survival from 68.6% of 303 reported cases in 2002 to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8429855/

Maternal hyperoxygenation in congenital heart disease - PMC Those with underdeveloped left-sided cardiac structures have the lowest one-year survival rate at 17.4% despite improvements in prenatal diagnosis, corrective ...

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.125.042014

Fetal Cerebrovascular Response to Maternal Hyperoxia ... Lack of fetal cerebrovascular response to MH is associated with smaller total brain volume beginning in utero in hypoplastic left heart syndrome ...

8. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.27657

Safety and feasibility pilot study of continuous low‐dose ... In this pilot phase-1 study, continuous low-dose MSO was found to be safe and feasible for pregnancies diagnosed with fetal SVP from the early third trimester ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38629477/

Safety and feasibility pilot study of continuous low-dose ... This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP.