Renal Anhydramnios Fetal Therapy (RAFT)

• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

Early pregnancy renal anhydramnios or 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.

Condition or disease	Intervention/treatment	Phase
Bilateral Renal Agenesis; Oligohydramnios; Anhydramnios; Potter Syndrome; Lung Hypoplasia; Multicystic Dysplastic Kidney; Multicystic Renal Dysplasia, Bilateral; Lower Urinary Tract Obstructive Syndrome; Fetal Renal Anomaly	Procedure: Serial amnioinfusions with isotonic fluid; Device: Spinal needle; Drug: Isotonic fluid	Not Applicable

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	100 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	All eligible patients will be offered participation in the study. Particpants can elect for invasive therapy with amnioinfusions or expectant management.
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Renal Anhydramnios Fetal Therapy (RAFT) Trial
Actual Study Start Date :	March 18, 2017
Estimated Primary Completion Date :	March 18, 2020
Estimated Study Completion Date :	March 18, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Serial amnioinfusions with isotonic fluid; Patients will undergo amnioinfusions with isotonic fluid every 1-2 weeks. 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; 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.; Other Name: Renal Anhydramnios Fetal Therapy (RAFT); Device: Spinal needle; 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.; Other Name: Obstetrics and gynecology needle; Drug: Isotonic fluid; 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.; Other Names: Normal saline; Lactated ringers solution
No Intervention: Expectant; Patients will be observed serially by ultrasound, fetal echocardiogram and MRI. Standard postnatal care will occur at a RAFT center.

Outcome Measures

Primary Outcome Measures :

1. Survival to successful dialysis [ Time Frame: Birth to either successful dialysis or nonsurvival. ]
   To evaluate the efficacy of serial saline amnioinfusions to prevent lethal pulmonary hypoplasia in patients with EPRA. Survival or nonsurvival to the endpoint of successful dialysis defined as 15 continuous days of dialysis catheter usage will be measured.

Secondary Outcome Measures :

1. Maternal safety: the rate of maternal adverse events [ Time Frame: These outcomes will be measured at every prenatal visit, after every prenatal procedure, at delivery and 30 days after delivery. ]
   To evaluate the safety of serial amnioinfusions in patients with EPRA. Safety of the infusions will be determined by the rate of maternal adverse events (if any) with infusion. superficial wound infection requiring antibiotics, bleed requiring transfusion, and death.
2. Number of serial amnioinfusions before preterm premature rupture of membranes or preterm delivery. [ Time Frame: Pregnancy ]
   To evaluate the feasibility of serial amnioinfusions without rupture of membranes or preterm birth for EPRA pregnancies.
3. Survival to transplant [ Time Frame: Birth to either successful renal transplant (usually around 2 years of life) or nonsurvival ]
   To determine the proportion of patients treated with RAFT who successfully receive renal transplant.
4. Quality of life using Pediatric Quality of Life Inventory 4.0 (PedsQL TM) survey [ Time Frame: 1 and 2 years of life and then 1, 2 3 and 4 years after transplant ]
   To determine the quality of life of patients that undergo RAFT. The parent proxy score will be used until the child is 5 years of age.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	Female
Gender Based Eligibility:	Yes
Gender Eligibility Description:	Pregnant women are the focus of this study
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Confirmed anhydramnios before 22 weeks GA for patients with FRF or confirmed diagnosis of CoBRA
• Eligible for first amnioinfusion before 26 weeks GA
• Confirmation that the expectant mother does not wish to undergo termination of the pregnancy
• Age greater than 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.

Exclusion Criteria:

• Cervix less than 2.5 cm in length
• Abnormal 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

Contacts and Locations

Contacts

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Contact: Eric B Jelin, MD	4432873384	ejelin1@jhmi.edu
Contact: Ahmet Baschat	844-JHFETAL	abascha1@jhmi.edu

Locations

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United States, Maryland
Johns Hopkins Hospital	Recruiting
Baltimore, Maryland, United States, 21287
Contact: Eric B Jelin, MD

Sponsors and Collaborators

Johns Hopkins University

Investigators

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Principal Investigator:	Eric B Jelin, MD	Johns Hopkins University

More Information

Additional Information:

The Center for Fetal Therapy  Johns Hopkins Children's Center Fetal Program 

Publications of Results:

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):413-5. doi: 10.1097/AOG.0000000000000339.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 Mar 21:1-8. doi: 10.1159/000497472. [Epub ahead of print] Review.

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Responsible Party:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT03101891 History of Changes
Other Study ID Numbers:	IRB00164021
First Posted:	April 5, 2017
Last Update Posted:	February 27, 2019
Last Verified:	February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Johns Hopkins University:

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

Additional relevant MeSH terms:

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Syndrome; Oligohydramnios; Congenital Abnormalities; Kidney Diseases; Multicystic Dysplastic Kidney; Hydronephrosis; Ureteral Obstruction	Disease; Pathologic Processes; Pregnancy Complications; Urologic Diseases; Urogenital Abnormalities; Kidney Diseases, Cystic; Ureteral Diseases