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

Trial Summary

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 data supports the effectiveness of the treatment Serial Amnioinfusions for Pulmonary Hypoplasia Due to Renal Conditions?

Research shows that serial amnioinfusions can help prevent lung underdevelopment in babies with certain kidney problems by restoring amniotic fluid, which is important for lung growth. Studies have reported cases where this treatment improved survival rates and allowed for further medical interventions like dialysis and kidney transplants. ^{1 2 3 4 5}

Is amnioinfusion generally safe for humans?

Amnioinfusion is generally considered safe with few adverse effects, as noted in studies and reviews, although rare complications like amniotic fluid embolism have been reported. ^{1 2 3 6 7}

How is the treatment of serial amnioinfusions unique for pulmonary hypoplasia due to renal conditions?

Serial amnioinfusions are unique because they involve repeatedly adding fluid to the amniotic sac to help the baby's lungs develop when there is not enough amniotic fluid due to kidney problems. This approach is different from other treatments because it directly addresses the lack of amniotic fluid, which is crucial for lung development, potentially improving survival rates in conditions that are otherwise considered lethal. ^{1 2 4 5 7}

What is the purpose of this trial?

Congenital lower urinary tract obstruction (LUTO) is a heterogeneous group of congenital anomalies that lead bladder outlet obstruction. If a complete obstruction is present, the perinatal mortality is estimated to be as high as 90% because of severe pulmonary hypoplasia due to the lack of amniotic fluid. Survivors have significant risk of renal impairment (90%) requiring dialysis or renal transplantation if no fetal intervention is performed. Renal agenesis is the congenital absence of one or both kidneys due to complete failure of the kidney to form. As many as 33% of fetuses with bilateral renal agenesis are stillborn, and the rest of them die immediately after birth due to severe pulmonary hypoplasia. The objective of the serial amnioinfusions for fetuses with these conditions will be to reduce the severity of pulmonary hypoplasia (regenerating the lung functionality) and therefore increase the chance that the newborn survives to begin peritoneal dialysis. Although there is initial evidence that serial amnioinfusions are feasible for the pregnant women and the fetuses, there is still a need to have a prospective clinical trial to confirm the hypothesis that serial amnioinfusions could prevent severe pulmonary hypoplasia allowing the newborns with bilateral renal agenesis or severe LUTO to survive to begin peritoneal dialysis. Therefore, the investigators aim to study the hypothesis that serial amnioinfusions for fetuses with severe LUTO and renal failure and those with bilateral renal agenesis will reduce the severity of pulmonary hypoplasia and therefore increase the chance that the newborn survives to begin peritoneal dialysis.

Research Team

Mauro Schenone, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios. [2011]

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

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial. [2023]

3. Switzerland 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. [2021]

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

Amnioinfusion for prevention of pulmonary hypoplasia in second-trimester rupture of membranes. [2013]

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

Successful in utero intervention for bilateral renal agenesis. [2021]

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

Amniotic fluid embolism after saline amnioinfusion: two cases and review of the literature. [2015]

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

Fetal Therapy for Renal Anhydramnios. [2023]