Amnioinfusion for Pulmonary Hypoplasia Due to Renal Conditions

Overseen By Jainnee McCann

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Disqualifiers: Fetal anomaly, Preterm labor, Placental abnormalities, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 16 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether serial amnioinfusions—a procedure where fluid is repeatedly injected into the amniotic sac—can aid babies with severe lung underdevelopment due to kidney issues. The goal is to determine if this treatment can improve the baby's survival chances by enhancing lung function, enabling dialysis after birth. Pregnant women carrying a single fetus diagnosed with severe lower urinary tract obstruction or missing both kidneys before 26 weeks of pregnancy may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that serial amnioinfusions are safe for fetuses with severe LUTO or bilateral renal agenesis?

Research has shown that serial amnioinfusions can be a safe treatment for unborn babies with serious conditions like lower urinary tract obstruction (LUTO) or missing kidneys (bilateral renal agenesis). Past studies demonstrated that this treatment reduces the risk of severe, life-threatening lung problems. The procedure involves injecting Lactated Ringer's Solution into the womb, and studies have found it is usually well-tolerated by both mother and baby.

It is important to understand that, like any medical procedure, risks may exist. Some reports indicate that while serial amnioinfusions can improve survival rates, babies may still face other health challenges. However, evidence suggests that the increased chance of survival can outweigh potential risks. This information is based on research findings and ongoing studies, which aim to confirm the safety and effectiveness of this promising treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about serial amnioinfusions for pulmonary hypoplasia due to renal conditions because this approach offers a novel way to support fetal lung development. Unlike current options, which typically focus on managing symptoms after birth, amnioinfusions involve injecting a lactated Ringer's solution directly into the amniotic sac. This procedure aims to create a more supportive environment for the fetus by increasing amniotic fluid levels, potentially promoting better lung growth before birth. By intervening during pregnancy, this method could improve outcomes for babies with severe conditions like lower urinary tract obstruction (LUTO) or bilateral renal agenesis, offering hope for conditions that currently have limited prenatal treatment options.

What evidence suggests that serial amnioinfusions might be an effective treatment for pulmonary hypoplasia?

Research has shown that repeated amnioinfusions, a procedure where fluid is added to the amniotic sac, can improve lung development in unborn babies with serious urinary and kidney problems. In this trial, participants will receive serial amnioinfusions to assess their effectiveness. Studies have found that this treatment can increase the chances of these babies surviving long enough to begin kidney treatment called peritoneal dialysis. This method has been used in cases where babies are missing both kidneys or have severe blockages in their urinary tract, which often lead to fatal lung issues. Early results suggest that this treatment can improve lung function and survival rates in these high-risk situations. However, these treatments are complex and require further research to confirm their benefits. ^{1 3 4 5 6}

Who Is on the Research Team?

Mauro Schenone, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for pregnant women over 18 with a single fetus under 26 weeks old, diagnosed with severe LUTO and renal failure or bilateral renal agenesis. The fetus must not have chromosome abnormalities or associated anomalies, and the mother should test negative for Hepatitis B, C, and HIV. Women at high risk of preterm labor or with certain medical conditions are excluded.

Inclusion Criteria

Mother meets psychosocial criteria that allows her to make a conscious decision about her fetus/infant

My unborn baby has severe urinary tract obstruction and kidney failure before 26 weeks.

My unborn baby does not have any chromosome abnormalities.

Exclusion Criteria

Participation in this clinical trial during a previous pregnancy

I have chosen not to undergo invasive tests.

You have a higher chance of having a baby born too early because of a short cervix, previous early births, or other related issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Serial ultrasound-guided amnioinfusion procedures performed weekly on fetuses diagnosed with severe LUTO or bilateral renal agenesis

Up to 16 weeks

Weekly visits for amnioinfusion procedures

Monitoring

Weekly ultrasound monitoring of amniotic fluid index (AFI) and continuation of amnioinfusion if AFI is <2 cm

Until 34 weeks of gestation

Follow-up

Infants followed for 24 months post-birth by a multi-specialty team including neonatologist, pediatric nephrology, and transplant team

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Serial Amnioinfusions

Trial Overview The study tests whether injecting Lactated Ringers Solution into the amniotic fluid can help regenerate lung function in fetuses with kidney issues leading to low amniotic fluid levels. This could increase their survival chances after birth to start dialysis treatments.

How Is the Trial Designed?

Group I: Amnioinfusion Experimental Treatment 1 Intervention

Lactated Ringers Solution for Injection --- Serial ultrasound-guided amnioinfusion procedures will be performed on fetuses having severe LUTO or bilateral renal agenesis that are diagnosed between 18 0/7-25 6/7 weeks.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Amnioinfusions have shown promise in treating early pregnancy renal anhydramnios (EPRA), with some fetuses surviving the neonatal period and successfully undergoing dialysis and kidney transplants, suggesting potential for improved outcomes.

There are currently no reports of untreated EPRA survivors, highlighting the critical need for rigorous prospective trials to evaluate the efficacy of amnioinfusions and other fetal therapies for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amnioinfusions to Treat Early Onset Anhydramnios Caused by Renal Anomalies: Background and Rationale for the Renal Anhydramnios Fetal Therapy Trial. O'Hare, EM., Jelin, AC., Miller, JL., et al.[2021]

Serial amnioinfusions initiated before 26 weeks' gestation in 21 maternal-fetal pairs with anhydramnios due to fetal bilateral renal agenesis showed a high live birth rate of 94%, with 82% of live-born infants surviving to at least 14 days after birth.

Despite the initial success in mitigating lethal pulmonary hypoplasia, only 35% of the neonates survived to hospital discharge, indicating significant long-term mortality and morbidity risks that need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial. Miller, JL., Baschat, AA., Rosner, M., et al.[2023]

In a study involving 32 fetal lambs, serial amnioinfusions through a subcutaneously implanted catheter significantly prevented pulmonary hypoplasia in cases of complete urinary tract obstruction, as indicated by better lung volume to body weight ratios compared to untreated controls.

The results suggest that using an intraamniotic port-a-cath for amnioinfusions could be a practical treatment for oligohydramnios, potentially improving outcomes for fetuses at risk of severe lung development issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios. Nicksa, GA., Yu, DC., Kalish, BT., et al.[2011]

The RAFT trial is investigating the safety and effectiveness of serial amnioinfusions in pregnancies affected by severe congenital kidney anomalies, aiming to restore amniotic fluid and prevent pulmonary hypoplasia.

Detailed anatomical and genetic assessments are crucial for determining which pregnancies may benefit from fetal interventions, given the high likelihood of additional anomalies and syndromes in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal Therapy for Renal Anhydramnios. Miller, JL., Baschat, AA., Atkinson, MA.[2023]

Transabdominal amnioinfusion in women with preterm premature rupture of membranes and persistent oligohydramnios significantly reduced the prevalence of pulmonary hypoplasia at birth, with rates of 46% in the amnioinfused group compared to 86% in the control group, based on a cohort study of 34 participants.

No complications related to the amnioinfusion procedure were reported, indicating it is a safe intervention, and successful amnioinfusions (lasting over 48 hours) were associated with better outcomes, suggesting that the duration of oligohydramnios correction may be crucial for preventing pulmonary hypoplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amnioinfusion for prevention of pulmonary hypoplasia in second-trimester rupture of membranes. Vergani, P., Locatelli, A., Strobelt, N., et al.[2013]

A case of bilateral renal agenesis was successfully managed with serial amnioinfusion, which helped improve fetal lung development and allowed the newborn to survive the critical newborn period.

The newborn, now 9 months old, is undergoing peritoneal dialysis as a bridge to planned renal transplantation, demonstrating the potential of amnioinfusion in enhancing outcomes for similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful in utero intervention for bilateral renal agenesis. Bienstock, JL., Birsner, ML., Coleman, F., et al.[2021]

Two cases of fatal amniotic fluid embolism occurred in women who underwent saline amnioinfusion during labor, particularly after thick meconium staining was observed, raising concerns about the safety of this intervention in such situations.

While amniotic fluid embolism is rare, the cases suggest a potential link between amnioinfusion and increased risk, especially in the presence of rapid labor and meconium-stained fluid, warranting further investigation without immediate changes to clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic fluid embolism after saline amnioinfusion: two cases and review of the literature. Maher, JE., Wenstrom, KD., Hauth, JC., et al.[2015]

Citations

1. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.6850

Serial Amnioinfusion Therapy for Treatment of Congenital ... Serial amnioinfusion therapy (SAT) is used to mitigate pulmonary hypoplasia (PH) in fetuses with bilateral renal agenesis (BRA). ◦. Perinatal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7411166/

Serial Amnioinfusion as Regenerative Therapy for Pulmonary ... The aim of this study was to investigate the effect of serial amnioinfusion therapy (SAT) for pulmonary hypoplasia in lower urinary tract ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03723564

Study Details | NCT03723564 | Serial Amnioinfusions As ... This study will offer serial amnioinfusions for patients with LUTO or bilateral renal agenesis. Due to the rarity and complexity of these cases, the ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2812481

Neonatal Survival After Serial Amnioinfusions for Bilateral ... Prenatal serial amnioinfusions can mitigate neonatal lethal pulmonary hypoplasia in neonates with bilateral renal agenesis, but infants face substantial ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38051327/

The Renal Anhydramnios Fetal Therapy Trial - PubMed - NIH Conclusions and relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/10698620

Neonatal Survival After Serial Amnioinfusions for Bilateral ... This prospective, nonrandomized clinical trial assesses neonatal outcomes after serial amnioinfusions initiated before 26 weeks' gestation to ...