Clinical trial NCT06728228: Amnioinfusion for Fetal Renal Failure
Official title: Amnioinfusion for Fetal Renal Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multicystic Dysplastic Kidney
Polycystic Kidney Disease
Fetal Renal Anomaly
Anhydramnios
Potter Syndrome
Lung Hypoplasia
Multicystic Renal Dysplasia, Bilateral
Lower Urinary Tract Obstructive Syndrome
Bilateral Renal Agenesis
Keywords: Fetal Renal Failure
Kidney Disease
MCDK
PCKD
Lead sponsor: Fetal Care Center, PLLC
Sponsor class: INDUSTRY
Collaborators: name: Medical City Children's Hospital
name: Medical City Women's Hospital
First posted: 2024-12-11
Enrollment: 35
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if serial amnioinfusions can improve the chances of survival for fetuses with severe kidney problems that cause low amniotic fluid (anhydramnios). Low amniotic fluid can affect lung development and may lead to serious health issues for the fetus. The main questions this study aims to answer are:

* Can serial amnioinfusion increase the chances of survival for these fetuses?
* Does this procedure improve chances of survival until dialysis and/or kidney transplant?

Participants will:

* Receive regular amnioinfusions, which is a procedure that adds fluid to the amniotic cavity.
* Undergo monitoring to check the effects on the fetus and mother.

This study will help researchers understand if amnioinfusion is a useful treatment for fetal kidney problems and may provide valuable information for similar cases in the future.

Detailed description: Fetal renal failure (FRF) is a severe and life-threatening condition caused by congenital abnormalities or inherited kidney diseases. In the womb, when the kidneys fail to function properly, this leads to a condition called anhydramnios-a complete lack of amniotic fluid. Amniotic fluid is essential for the fetus's lung development, particularly during the canalicular phase of pulmonary development, which occurs between 16 and 28 weeks of gestation. Without sufficient amniotic fluid, the lungs cannot develop properly, resulting in a condition known as pulmonary hypoplasia. Severe hypoplasia has previously been described as almost always fatal, typically leading to neonatal death shortly after birth.

In recent years, promising advances in fetal therapies have opened new doors for treating conditions that were once considered untreatable. One such intervention involves serial amnioinfusion, a procedure where sterile saline or another isotonic fluid is injected into the amniotic sac to restore fluid levels. Early studies, including the RAFT trial (Renal Anhydramnios Fetal Therapy), have demonstrated that this approach may improve survival rates by promoting lung development in fetuses with FRF. Building upon these findings, this study seeks to further evaluate the safety and effectiveness of serial amnioinfusion in improving neonatal outcomes for families facing this diagnosis.

This study will enroll approximately 60 pregnant individuals carrying singleton pregnancies complicated by FRF and anhydramnios. Participants will be divided into two groups: an intervention group, which will receive serial amnioinfusion procedures as deemed appropriate by the study doctor, and a control group, which will not undergo interventions and will receive comfort care for their pregnancies. The primary goals of the study are to evaluate maternal safety, assess fetal survival to dialysis, and determine survival to kidney transplant eligibility.

The amnioinfusion procedures will be performed at the Fetal Care Center by a team of experts in fetal procedures. To ensure patient safety, the study includes a rigorous monitoring plan to track any potential adverse events in real time. Data from imaging studies (e.g., ultrasound, echocardiogram, MRI) and laboratory biomarkers will be collected to evaluate fetal and maternal responses to the treatment. While the study focuses on improving outcomes for individual patients, it also has broader implications for science and society. By systematically analyzing the benefits and risks of serial amnioinfusion, this research could help refine treatment protocols and set the stage for new standards of care for FRF. For the families involved, participation in this study offers the possibility of improved survival for their children, with potential eligibility for life-saving kidney transplants in the future.

This study represents a critical step toward addressing a condition that has long been considered untreatable. Through collaboration, innovation, and rigorous research, the team aims to provide hope for families affected by FRF.

Eligibility criteria: Inclusion criteria:

1. Confirmed anhydramnios before 22 weeks GA for patients with FRF.
2. Consent is signed and first therapeutic amnioinfusion can and does occur before 28 weeks and 6/7 days GA.
3. Confirmation that the expectant mother understands her options for management of the pregnancy.
4. Age ≥18 years of age.
5. Willingness to be followed by the Fetal Care Center at Dallas and deliver at Medical City Dallas.
6. Willingness for postnatal care to be performed at Medical City Dallas Hospital/the Fetal Care Center until maternal discharge.
7. Consults with Pediatric Nephrology, Neonatology, Transplant Surgery, Pediatric surgery, Maternal-Fetal Medicine Specialist, and a Genetic Counselor.

Exclusion criteria:

1. Cervix less than 2.5 cm in length.
2. No fatal findings on Karyotype (e.g trisomy 13, or 18) or Microarray fatal findings excluding those that are related to pulmonary hypoplasia due to fetal renal failure (e.g. Meckel-Gruber, PCKD).
3. Other significant congenital anomalies in the fetus.
4. Evidence of chorioamnionitis or abruptio placentae.
5. Evidence of rupture of membranes or chorionic-amniotic separation.
6. Evidence of preterm labor.
7. Multiple gestation.
8. Severe maternal medical condition in pregnancy.
9. Clinically diagnosed maternal depression, psychoses, or anxiety that are refractory to treatment.
10. Technical limitations precluding amnioinfusion.

Primary outcomes:
measure: Fetal Survival to Dialysis
timeFrame: Birth to either survival to >=14 days and placement of dialysis access, or nonsurvival, up to 3 weeks.
measure: Fetal Survival to Transplant
timeFrame: >=2 years after delivery.
measure: Incidence of Maternal Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: From enrollment in the study through delivery and up to 30 days postpartum.
Secondary outcomes:
measure: Number of infusions prior to rupture of membranes among participants in the intervention group
timeFrame: During the pregnancy, up to 9 months
measure: Mean gestational age at rupture of membranes in the intervention group
timeFrame: During the pregnancy, up to 9 months
measure: Mean gestational age at delivery in the intervention group
timeFrame: During the pregnancy, up to 9 months
measure: Rate of fetal demise in utero among participants in the non-intervention group
timeFrame: During the pregnancy, up to 9 months
measure: Mean gestational age at delivery in the non-intervention group
timeFrame: During the pregnancy, up to 9 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Fetal Care Center
state: Texas
Study officials:
References:
citation: Miller JL, Baschat AA, Rosner M, Blumenfeld YJ, Moldenhauer JS, Johnson A, Schenone MH, Zaretsky MV, Chmait RH, Gonzalez JM, Miller RS, Moon-Grady AJ, Bendel-Stenzel E, Keiser AM, Avadhani R, Jelin AC, Davis JM, Warren DS, Hanley DF, Watkins JA, Samuels J, Sugarman J, Atkinson MA. Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial. JAMA. 2023 Dec 5;330(21):2096-2105. doi: 10.1001/jama.2023.21153.
citation: O'Hare EM, Jelin AC, Miller JL, Ruano R, Atkinson MA, Baschat AA, Jelin EB. Amnioinfusions to Treat Early Onset Anhydramnios Caused by Renal Anomalies: Background and Rationale for the Renal Anhydramnios Fetal Therapy Trial. Fetal Diagn Ther. 2019;45(6):365-372. doi: 10.1159/000497472. Epub 2019 Mar 21.