Renal Anhydramnios Fetal Therapy

NCT03101891 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB00164021R01HD100540
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 9

Brief Summary

Early pregnancy renal anhydramnios (EPRA) is a condition where a pregnant woman does not have any amniotic fluid around her fetus because of a problem with the fetus's kidneys. This condition is thought to be fatal once the fetus is born because of inadequate lung growth. The Renal Anhydramnios Fetal Therapy (RAFT) Trial offers eligible pregnant women with a diagnosis of EPRA an experimental therapy of repeated or serial "amnioinfusions" of fluid into the womb. An amnioinfusion involves placing a small needle through the pregnant woman's skin into the womb next to the fetus. Warm sterile fluid with balanced electrolytes and antibiotics is then slowly infused into amniotic space inside the womb. The aim is to help the fetus's lungs grow enough so he or she can survive after birth. These amnioinfusions will be carried out by an expert in fetal interventions at a RAFT center. There is a significant risk of early rupture of membranes and early delivery in subjects who receive amnioinfusions, and any potential trial participants will be counseled about these risks before they decide whether to join the trial. Any eligible patients who, after counseling, elect to terminate the pregnancy will not be eligible to participate in the trial. All eligible patients who choose to join the RAFT trial will be able to choose their assignment into one of two arms of the study: (1) to receive serial amnioinfusions (2) to not receive amnioinfusions but receive monitoring for the remainder of the pregnancy at the RAFT center. Thus, assignment of patients to study arm will not be random, but will be decided by the participant. Fetuses who do survive after birth will require intensive medical management for kidney failure including placement of a dialysis catheter and dialysis therapy with the eventual need for a kidney transplant. Treatment for lung disease secondary to abnormal lung development may also be required. The study will follow babies and their families until non-survival or transplant. Update: Due to recommendations from the RAFT trial Data and Safety Monitoring Board, the trial is no longer open to enrollment for pregnancies complicated by bilateral renal agenesis as of July 19, 2022. Enrollment for patients with pregnancies complicated by other causes of fetal renal failure remains open.

Conditions

Anhydramnios; Potter Syndrome; Lung Hypoplasia; Multicystic Dysplastic Kidney; Multicystic Renal Dysplasia, Bilateral; Lower Urinary Tract Obstructive Syndrome; Fetal Renal Anomaly

Keywords

Amnioinfusion; Fetal therapy; Bilateral Renal Agenesis; Fetal Renal Failure; Lower Urinary Tract Obstruction (LUTO); Anhydramnios

Outcome Measures

Primary Outcomes (1)

• Proportion of neonates surviving to >= 14 days and placement of dialysis access after serial amnioinfusions

  The proportion of neonates who survive to \>= 14 days and placement of dialysis access as well as the exact confidence interval will be presented for CoBRA and fetal renal failure (FRF) patients separately in the intervention group.

  Birth to either survival to >=14 days and placement of dialysis access, or nonsurvival, up to 3 weeks

Secondary Outcomes (6)

• Number of infusions before rupture of membrane among those in the intervention arm

  During the EPRA pregnancy, up to 9 months

• Mean gestational age at the time of rupture of membrane among those in the intervention arm

  During the EPRA pregnancy, up to 9 months

• Mean gestational age at delivery among those in the intervention arm

  During the EPRA pregnancy, up to 9 months

• Rate of in utero fetal demise among those in the non-intervention arm

  During the EPRA pregnancy, up to 9 months

• Mean gestational age at delivery among those in the non-intervention arm

  During the EPRA pregnancy, up to 9 months

Study Arms (2)

Serial amnioinfusions with isotonic fluid

EXPERIMENTAL

There are two interventional arms to the trial. Recruitment in the bilateral renal agenesis arm of the trial was stopped in July 2022 after Data Safety Monitoring Board (DSMB) review. Recruitment is ongoing in the non-bilateral renal agenesis, fetal renal failure with anhydramnios arm of the trial. Patients will undergo amnioinfusions with isotonic fluid every 2-12 days.. A spinal needle will be used to perform the infusion. The latest infusions will begin is 26 weeks gestation. Standard postnatal care will occur at a RAFT center.

Procedure: Serial amnioinfusions with isotonic fluid; Device: Spinal needle; Drug: Isotonic fluid

Expectant

NO INTERVENTION

Patients will be observed serially by ultrasound, fetal echocardiogram and MRI. Standard postnatal care will occur at a RAFT center.

Interventions

Serial amnioinfusions with isotonic fluid PROCEDURE

Amnioinfusions will be performed by an expert in fetal procedures with a 20 or 22 gauge needle using sterile technique and ultrasound guidance. Local anesthetic will be employed. The fluid will consist of warmed isotonic fluid. Infusions may take up to 1 hour.

Also known as: Renal Anhydramnios Fetal Therapy (RAFT)

Serial amnioinfusions with isotonic fluid

Spinal needle DEVICE

A 20 or 22 gauge spinal needle will be used with sterile technique to access the uterus under ultrasound guidance and to infuse isotonic fluid.

Also known as: Obstetrics and gynecology needle

Serial amnioinfusions with isotonic fluid

Isotonic fluid DRUG

Isotonic fluids, including normal saline or lactated ringers solution, will be infused into the uterus through a spinal needle under ultrasound guidance using sterile technique. This fluid will act as replacement amniotic fluid.

Also known as: Normal saline, Lactated ringers solution

Serial amnioinfusions with isotonic fluid

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pregnant women are the focus of this study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed anhydramnios before 22 weeks gestational age (GA) for patients with fetal renal failure (excluding bilateral renal agenesis)
• Consent is signed and first therapeutic amnioinfusion can and does occur before 26 weeks and 0 days GA
• Confirmation that the expectant mother does not wish to undergo termination of the pregnancy
• Age ≥ 18 years of age for expectant mothers
• Willingness to be followed and deliver at a RAFT center
• Willingness for postnatal care to be performed at a RAFT center until discharge
• Completed consults with Pediatric Nephrology, Neonatology, Transplant Surgery, Pediatric surgery, Maternal-Fetal Medicine Specialist, and Licensed Clinical Social Worker and a Genetic Counselor

You may not qualify if:

• Cervix less than 2.5 cm in length
• No significant pathogenic or likely significant pathogenic findings on Karyotype or Microarray
• Other significant congenital anomalies in the fetus
• Evidence of chorioamnionitis or abruptio placentae
• Evidence of rupture of membranes or chorioamniotic separation
• Evidence of preterm labor
• Multiple gestation
• Severe maternal medical condition in pregnancy.
• Maternal depression as assessed by a Beck Depression Inventory score equal to or greater than 17 that is refractory to treatment
• Technical limitations precluding amnioinfusion

Sponsors & Collaborators

• Johns Hopkins University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (9)

University of Southern California/Children's Hospital of Los Angeles/Huntington Hospital

Los Angeles, California, 90033, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (5)

• 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.

  PMID: 30897573 BACKGROUND

• Huber C, Shazly SA, Blumenfeld YJ, Jelin E, Ruano R. Update on the Prenatal Diagnosis and Outcomes of Fetal Bilateral Renal Agenesis. Obstet Gynecol Surv. 2019 May;74(5):298-302. doi: 10.1097/OGX.0000000000000670.

  PMID: 31098643 BACKGROUND

• Bienstock JL, Birsner ML, Coleman F, Hueppchen NA. Successful in utero intervention for bilateral renal agenesis. Obstet Gynecol. 2014 Aug;124(2 Pt 2 Suppl 1):413-415. doi: 10.1097/AOG.0000000000000339.

  PMID: 25004316 RESULT

• 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.

  PMID: 38051327 DERIVED

• Atkinson MA, Jelin EB, Baschat A, Blumenfeld YJ, Chmait RH, O'Hare E, Moldenhauer JS, Zaretsky MV, Miller RS, Ruano R, Gonzalez JM, Johnson A, Mould WA, Davis JM, Hanley DF, Keiser AM, Rosner M, Miller JL. Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial. Clin Ther. 2022 Aug;44(8):1161-1171. doi: 10.1016/j.clinthera.2022.07.001. Epub 2022 Jul 30.

  PMID: 35918190 DERIVED

Related Links

• The Center for Fetal Therapy

MeSH Terms

Conditions

Hereditary renal agenesis; Multicystic Dysplastic Kidney; Multicystic renal dysplasia, bilateral

Interventions

Saline Solution; Ringer's Lactate

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Meredith Atkinson

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All eligible patients will be offered participation in the study. Participants can elect for invasive therapy with amnioinfusions or expectant management.

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: April 5, 2017
• Study Start: December 21, 2018
• Primary Completion: March 10, 2025
• Study Completion (Estimated): February 28, 2030
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)