Amnioinfusion for Pulmonary Hypoplasia Due to Renal Conditions

Recruiting in Palo Alto (17 mi)

Overseen by Mauro Schenone, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mayo Clinic

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

No Placebo Group

Trial Summary

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.

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}

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.

Trial 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 (Regenerative Therapy)

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic Rochester, MN

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3427

Patients Recruited

3,221,000+

References

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

Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios. [2011] Severe neonatal pulmonary hypoplasia incurs mortality rates approaching 71% to 95%. We sought to determine the utility of serial amnioinfusions through a subcutaneously implanted intraamniotic catheter to prevent pulmonary hypoplasia in fetal obstructive uropathy.

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

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial. [2023] Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.

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] Anhydramnios caused by early anuria is thought to be universally fatal due to pulmonary hypoplasia. Bilateral renal agenesis and early fetal renal failure leading to anhydramnios constitute early pregnancy renal anhydramnios (EPRA). There have been successful reports of amnioinfusions to promote lung growth in the setting of EPRA. Some of these successfully treated EPRA fetuses have survived the neonatal period, undergone successful dialysis, and subsequently received a kidney transplant. Conversely, there are no reports of untreated EPRA survivors. This early success of amnioinfusions to treat EPRA justifies a rigorous prospective trial. The objective of this study is to provide a review of what is known about fetal therapy for EPRA and describe the Renal Anhydramnios Fetal Therapy trial. We review the epidemiology, pathophysiology, and genetics of EPRA. Furthermore, we have performed systematic review of case reports of treated EPRA. We describe the ethical framework, logistical challenges, and rationale for the current single center (NCT03101891) and planned multicenter trial.

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

Amnioinfusion for prevention of pulmonary hypoplasia in second-trimester rupture of membranes. [2013] We conducted a study to evaluate the feasibility and benefits of transabdominal amnioinfusion in preterm premature rupture of membranes with persistent oligohydramnios for the prevention of pulmonary hypoplasia. To this purpose, we designed a cohort study in which the pregnancy outcome of women with rupture of membranes at or = 4 days) oligohydramnios managed with serial amnioinfusions (n = 18) was compared with that of a historic cohort group (controls) with similar characteristics but managed expectantly (n = 16). Pulmonary hypoplasia was diagnosed at birth in the presence of strict radiological and pathological criteria. No amnioinfusion-related complications occurred. The prevalence of pulmonary hypoplasia was significantly lower among the amnioinfused cases compared with the controls (46% [6 of 13] vs 86% [12 of 14], odds ratio [OR] = 0.4, 95% confidence interval [CI] 0.2-0.9), despite a lower gestational age at rupture of membranes in the treated group. Within the group undergoing amnioinfusions, those in which the infused solution was rapidly lost had a higher rate of pulmonary hypoplasia compared with those in which amnioinfusion alleviated oligohydramnios for > 48 hours (considered successful) (0 of 4 vs. 6 of 9, OR = 2.3, 95% CI 1-5.5). Cases of successful amnioinfusion had a longer interval between membrane rupture and appearance of oligohydramnios than those in which the procedure failed to correct oligohydramnios, even though both groups had similar gestational age at appearance of oligohydramnios. This suggests that the rate of loss of amniotic fluid after membrane rupture may predict the rate of loss of the infused solution, and therefore identify a subset of patients who may benefit from the procedure.

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

Successful in utero intervention for bilateral renal agenesis. [2021] We report a case of bilateral renal agenesis treated with serial amnioinfusion in which the newborn survived the newborn period and was able to undergo peritoneal dialysis as a bridge to planned renal transplantation.

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

Amniotic fluid embolism after saline amnioinfusion: two cases and review of the literature. [2015] Amnioinfusion is an intrapartum intervention with proven benefit in certain clinical situations. It is thought to be a safe treatment with few adverse effects.

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

Fetal Therapy for Renal Anhydramnios. [2023] The most severe forms of congenital anomalies of the kidney and urinary tract present in fetal life with early pregnancy renal anhydramnios and are considered lethal due to pulmonary hypoplasia without fetal therapy. Due to the high rate of additional structural anomalies, genetic abnormalities, and associated syndromes, detailed anatomic survey and genetic testing are imperative when stratifying which pregnancies are appropriate for fetal intervention. Restoring amniotic fluid around the fetus is the principal goal of prenatal treatment. The ongoing multi-center Renal Anhydramnios Fetal Therapy (RAFT) trial is assessing the safety and efficacy of serial amnioinfusions to prevent pulmonary hypoplasia so that the underlying renal disease can be addressed.