AnhydramniosPhase 1RAFTNCT03101891
Renal Anhydramnios Fetal Therapy
A Phase 1 study testing Serial amnioinfusions with isotonic fluid, Spinal needle and Isotonic fluid in people with Anhydramnios and Potter Syndrome, run by Johns Hopkins University at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Anhydramnios, Potter Syndrome, Lung Hypoplasia
- What is being tested?
- Serial amnioinfusions with isotonic fluid, Spinal needle and Isotonic fluid
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 9 sitesUnited States
- Study dates
- 21 Dec 2018to 27 Feb 2026
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Colorado Denver
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Southern California/Children's Hospital of Los Angeles/Huntington Hospital
Los Angeles, California, 90033
Columbia University
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55902
University of California San Francisco
San Francisco, California, 94158
Stanford University
Stanford, California, 94305
About this study
Official title: Renal Anhydramnios Fetal Therapy (RAFT) Trial
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.
Read the detailed description
Amniotic fluid is critical for normal lung development. After the first trimester of pregnancy amniotic fluid is composed nearly completely of fetal urine. The absence of amniotic fluid due to lack of urine production by the fetal kidneys is known as anhydramnios. Early pregnancy renal anhydramnios or EPRA is thought to be 100% lethal after birth if left untreated because of neonatal respiratory failure. The two causes of EPRA are bilateral renal agenesis or fetal renal failure (such as from multicystic dysplastic kidneys or obstructed kidneys). Recently there have been clinical case reports of repeated or serial infusions of isotonic fluid (amnioinfusions) into the amniotic cavity leading to respiratory survival in neonates with a history of EPRA. Some surviving neonates have gone on to undergo successful dialysis and kidney transplant as toddlers. However, no prospective trial has investigated the safety of amnioinfusions in EPRA, the feasibility of doing serial amnioinfusions in EPRA pregnancies without causing rupture of membranes, or the neonatal survival rate after serial amnioinfusions for EPRA. Accordingly the goal of the Renal Anhydramnios Fetal Therapy (RAFT) trial is to determine the safety, feasibility, and efficacy of serial amnioinfusions to promote normal fetal lung development in EPRA. Pregnant patients presenting to a RAFT center with a diagnosis of EPRA will undergo an evaluation including diagnostic amnioinfusion with ultrasound imaging to verify the diagnosis. Counseling by a team of subspecialists including a maternal fetal medicine doctor, a pediatric nephrologist, a pediatric surgeon, a neonatologist, a kidney transplant specialist, a genetic counselor and a social worker will be given to every patient. This counseling is meant to provide the clearest picture possible of what serial amnioinfusions entail and what life will be like for a surviving neonate with no kidney function. Survivors will require urgent dialysis with a peritoneal or hemodialysis catheter. These children are prone to significant infections and often need a gastrostomy tube in order to receive sufficient nutrition. The goal is for these children to ultimately undergo the most robust form of renal replacement therapy with a kidney transplant once they are large enough to tolerate it.
Once the diagnosis of EPRA is confirmed, counseling is complete and a patient is deemed eligible for serial amnioinfusions, enrollment into the study will be offered. Patients may choose to enroll in the study, may choose to continue the pregnancy and not be a part of the study or may choose to terminate the pregnancy. If the patients elect to enroll in the study, they will be given a further choice of intervention with serial amnioinfusions or expectant management with repeat imaging. Participants will not be randomized because there is no realistic hope that expectant management will lead to postnatal survival. Patients who do not choose to undergo amnioinfusions but who also do not elect to terminate will provide invaluable insight into the in utero natural history of EPRA if they enroll in the trial. The sample size of this trial is based on a calculation of the number of patients required to adequately determine a postnatal survival rate of amnioinfusions for EPRA with narrow confidence intervals. Postnatal survival will be defined as survival for >=14 days and placement of dialysis access; this is the primary outcome measure. We have determined that 35 maternal/fetal participants are required in order to calculate a survival rate of anywhere from 20-80%. We plan to study two 35 participant cohorts of EPRA patients, those with EPRA from bilateral renal agenesis and those with EPRA from fetal renal failure. We will therefore aim for a total of 70 maternal/fetal pairs with EPRA to undergo serial amnioinfusions. Additionally we will aim to recruit 30 maternal/fetal pairs with EPRA in the expectant management group for a total of 100 participants.
During the prenatal portion of the trial we plan to collect a small specimen of amniotic fluid from participants in the amnioinfusion group during each amnioinfusion. This fluid will be assayed for different protein and lipid measures of lung maturity at a research lab at Johns Hopkins. Additionally, in both the amnioinfusion group and the expectant management group we will study ultrasound, MRI and echocardiogram measures of lung growth. We will correlate these biochemical and radiologic markers with survival in order to better understand who is likely to respond to amnioinfusions and why that response is occurring. We also plan to study several secondary and tertiary outcomes in our surviving EPRA patients. These outcomes include survival to discharge from a RAFT center, survival to transplant and quality of life measures for both participants and their families.
The changes made to the outcomes are due to the protocol amendment.
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
- Being tested
- Serial amnioinfusions with isotonic fluid, Spinal needle, Isotonic fluid
- Keywords
- Amnioinfusion, Fetal therapy, Bilateral Renal Agenesis, Fetal Renal Failure, Lower Urinary Tract Obstruction (LUTO), Anhydramnios
- Medical subject headings
- Hereditary renal agenesis, Multicystic Dysplastic Kidney, Multicystic renal dysplasia, bilateral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serial amnioinfusions with isotonic fluidProcedure or surgery
Also called Renal Anhydramnios Fetal Therapy (RAFT)
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.
Spinal needleDevice
Also called Obstetrics and gynecology 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.
Isotonic fluidDrug
Also called Normal saline, Lactated ringers solution
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neonates Surviving to >= 14 Days and Placement of Dialysis Access After Serial Amnioinfusions
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 FRF and BRA intervention.
Measured: Birth to either survival to >=14 days and placement of dialysis access, or nonsurvival, up to 3 weeks
Secondary outcomes (6)
Participants Who Experienced PPROM While Receiving Serial Amnioinfusions
The feasibility of serial amnioinfusions for EPRA will be assessed using the incidence of PPROM in the FRF and BRA intervention arms.
Measured: During the EPRA pregnancy
Median Time From First Amnioinfusion to PPROM in Those Receiving Serial Amnioinfusions
The feasibility of serial amnioinfusions for EPRA will be measured using the time from the first amnioinfusion to PPROM in the FRF and BRA arms.
Measured: During the EPRA pregnancy
Median Gestational Age at Delivery Among Those in the Intervention Arm
Investigators will assess the feasibility of the intervention by gestational age at delivery in the FRF and BRA arms.
Measured: During the EPRA pregnancy
Infants Surviving to Hospital Discharge in the FRF and BRA Intervention Arms
Assess the long-term efficacy of the intervention by infant survival to discharge
Measured: From birth until the date of hospital discharge, approximately 5 months
Rate of in Utero Fetal Demise in Those in the Non-intervention Arm
Natural history of ERPA pregnancy in non-intervention patients
Measured: Duration of Pregnancy
Rate of in Utero Fetal Demise in the Intervention Arm
Assess the feasibility of the intervention in terms of fetal survival
Measured: Length of pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study start21 Dec 2018
- Primary completion10 Mar 2025
- Study completion27 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AnhydramniosStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All eligible patients will be offered participation in the study. Participants can elect for invasive therapy with amnioinfusions or expectant management.
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Meredith Atkinson, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101891
- Sponsor's protocol ID
- IRB00164021
- Other IDs
- R01HD100540
- Acronym
- RAFT
- Status last verified
- Jun 2026
- First submitted
- 27 Mar 2017
- Last updated
- 1 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30897573Huber 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.
PubMed 31098643Bienstock 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.
PubMed 25004316Miller JL, Baschat AA, Johnson A, Blumenfeld YJ, Schenone MH, Gebb JS, Moldenhauer JS, Zaretsky MV, Chmait RH, Gonzalez JM, Miller RS, Krispin E, Shamshirsaz A, Bligard KH, Kalan AM, Sanz Cortes M, Moon-Grady AJ, Bendel-Stenzel E, Menon S, Wong C, Grimm P, Kwak C, Gallup J, McKenna KJ, Marron L, Hanna C, Tran CL, Behrendt NJ, Galan HL, Samuels J, Swinford R, Keiser AM, Rosner M, Kush ML, Nasr I, Vasu S, Boss RD, Jelin AC, Thompson RE, Davis JM, Warren DS, Hanley DF, Atkinson MA. Neonatal Survival After Serial Amnioinfusions for Anhydramnios Due to Fetal Kidney Failure: The RAFT Clinical Trial. JAMA. 2026 Jul 1:e268568. doi: 10.1001/jama.2026.8568. Online ahead of print.
PubMed 42384373Lammert DB, Miller JL, Atkinson MA, Sun LR. Single-Center Incidence and Patterns of Stroke in Early Renal Anhydramnios After Serial Amnioinfusions. J Pediatr. 2024 Aug;271:114053. doi: 10.1016/j.jpeds.2024.114053. Epub 2024 Apr 12.
PubMed 38615944Miller 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.
PubMed 38051327Atkinson 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.
PubMed 35918190
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal Anhydramnios Fetal Therapy (RAFT) Trial
- ClinicalTrials.gov ID
- NCT03101891
- Acronym / sponsor ID
- RAFT / IRB00164021
- Conditions
- Anhydramnios, Potter Syndrome, Lung Hypoplasia, Multicystic Dysplastic Kidney, Multicystic Renal Dysplasia, Bilateral, Lower Urinary Tract Obstructive Syndrome
- Keywords
- Amnioinfusion, Fetal therapy, Bilateral Renal Agenesis, Fetal Renal Failure, Lower Urinary Tract Obstruction (LUTO), Anhydramnios
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 21 Dec 2018 (actual)
- Primary completion
- 10 Mar 2025 (actual)
- Study completion
- 27 Feb 2026 (actual)
- First posted
- 5 Apr 2017 (actual)
- Results
- Posted 1 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Amniotic fluid is critical for normal lung development. After the first trimester of pregnancy amniotic fluid is composed nearly completely of fetal urine. The absence of amniotic fluid due to lack of urine production by the fetal kidneys is known as anhydramnios. Early pregnancy renal anhydramnios or EPRA is thought to be 100% lethal after birth if left untreated because of neonatal respiratory failure. The two causes of EPRA are bilateral renal agenesis or fetal renal failure (such as from multicystic dysplastic kidneys or obstructed kidneys). Recently there have been clinical case reports of repeated or serial infusions of isotonic fluid (amnioinfusions) into the amniotic cavity leading to respiratory survival in neonates with a history of EPRA. Some surviving neonates have gone on to undergo successful dialysis and kidney transplant as toddlers. However, no prospective trial has investigated the safety of amnioinfusions in EPRA, the feasibility of doing serial amnioinfusions in EPRA pregnancies without causing rupture of membranes, or the neonatal survival rate after serial amnioinfusions for EPRA. Accordingly the goal of the Renal Anhydramnios Fetal Therapy (RAFT) trial is to determine the safety, feasibility, and efficacy of serial amnioinfusions to promote normal fetal lung development in EPRA. Pregnant patients presenting to a RAFT center with a diagnosis of EPRA will undergo an evaluation including diagnostic amnioinfusion with ultrasound imaging to verify the diagnosis. Counseling by a team of subspecialists including a maternal fetal medicine doctor, a pediatric nephrologist, a pediatric surgeon, a neonatologist, a kidney transplant specialist, a genetic counselor and a social worker will be given to every patient. This counseling is meant to provide the clearest picture possible of what serial amnioinfusions entail and what life will be like for a surviving neonate with no kidney function. Survivors will require urgent dialysis with a peritoneal or hemodialysis catheter. These children are prone to significant infections and often need a gastrostomy tube in order to receive sufficient nutrition. The goal is for these children to ultimately undergo the most robust form of renal replacement therapy with a kidney transplant once they are large enough to tolerate it.
Once the diagnosis of EPRA is confirmed, counseling is complete and a patient is deemed eligible for serial amnioinfusions, enrollment into the study will be offered. Patients may choose to enroll in the study, may choose to continue the pregnancy and not be a part of the study or may choose to terminate the pregnancy. If the patients elect to enroll in the study, they will be given a further choice of intervention with serial amnioinfusions or expectant management with repeat imaging. Participants will not be randomized because there is no realistic hope that expectant management will lead to postnatal survival. Patients who do not choose to undergo amnioinfusions but who also do not elect to terminate will provide invaluable insight into the in utero natural history of EPRA if they enroll in the trial. The sample size of this trial is based on a calculation of the number of patients required to adequately determine a postnatal survival rate of amnioinfusions for EPRA with narrow confidence intervals. Postnatal survival will be defined as survival for >=14 days and placement of dialysis access; this is the primary outcome measure. We have determined that 35 maternal/fetal participants are required in order to calculate a survival rate of anywhere from 20-80%. We plan to study two 35 participant cohorts of EPRA patients, those with EPRA from bilateral renal agenesis and those with EPRA from fetal renal failure. We will therefore aim for a total of 70 maternal/fetal pairs with EPRA to undergo serial amnioinfusions. Additionally we will aim to recruit 30 maternal/fetal pairs with EPRA in the expectant management group for a total of 100 participants.
During the prenatal portion of the trial we plan to collect a small specimen of amniotic fluid from participants in the amnioinfusion group during each amnioinfusion. This fluid will be assayed for different protein and lipid measures of lung maturity at a research lab at Johns Hopkins. Additionally, in both the amnioinfusion group and the expectant management group we will study ultrasound, MRI and echocardiogram measures of lung growth. We will correlate these biochemical and radiologic markers with survival in order to better understand who is likely to respond to amnioinfusions and why that response is occurring. We also plan to study several secondary and tertiary outcomes in our surviving EPRA patients. These outcomes include survival to discharge from a RAFT center, survival to transplant and quality of life measures for both participants and their families.
The changes made to the outcomes are due to the protocol amendment.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All eligible patients will be offered participation in the study. Participants can elect for invasive therapy with amnioinfusions or expectant management.
| Arm | Type | Receives |
|---|---|---|
| Serial amnioinfusions with isotonic fluid | Experimental | Procedure: Serial amnioinfusions with isotonic fluid, Device: Spinal needle, Drug: Isotonic fluidThere 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. |
| Expectant | No intervention | –Patients will be observed serially by ultrasound, fetal echocardiogram and MRI. Standard postnatal care will occur at a RAFT center. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Serial amnioinfusions with isotonic fluidAlso: Renal Anhydramnios Fetal Therapy (RAFT)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. | Procedure or surgery | Serial amnioinfusions with isotonic fluid |
| Spinal needleAlso: Obstetrics and gynecology needleA 20 or 22 gauge spinal needle will be used with sterile technique to access the uterus under ultrasound guidance and to infuse isotonic fluid. | Device | Serial amnioinfusions with isotonic fluid |
| Isotonic fluidAlso: Normal saline, Lactated ringers solutionIsotonic 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. | Drug | Serial amnioinfusions with isotonic fluid |
Primary outcome
Neonates Surviving to >= 14 Days and Placement of Dialysis Access After Serial Amnioinfusions
Time frame: Birth to either survival to >=14 days and placement of dialysis access, or nonsurvival, up to 3 weeks
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 FRF and BRA intervention.
6 secondary outcomes
Participants Who Experienced PPROM While Receiving Serial Amnioinfusions
Time frame: During the EPRA pregnancy
Median Time From First Amnioinfusion to PPROM in Those Receiving Serial Amnioinfusions
Time frame: During the EPRA pregnancy
Median Gestational Age at Delivery Among Those in the Intervention Arm
Time frame: During the EPRA pregnancy
Infants Surviving to Hospital Discharge in the FRF and BRA Intervention Arms
Time frame: From birth until the date of hospital discharge, approximately 5 months
Rate of in Utero Fetal Demise in Those in the Non-intervention Arm
Time frame: Duration of Pregnancy
Rate of in Utero Fetal Demise in the Intervention Arm
Time frame: Length of pregnancy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30897573O'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.
- Background: PubMed 31098643Huber 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.
- Results publication: PubMed 25004316Bienstock 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.
- Derived from this study: PubMed 42384373Miller JL, Baschat AA, Johnson A, Blumenfeld YJ, Schenone MH, Gebb JS, Moldenhauer JS, Zaretsky MV, Chmait RH, Gonzalez JM, Miller RS, Krispin E, Shamshirsaz A, Bligard KH, Kalan AM, Sanz Cortes M, Moon-Grady AJ, Bendel-Stenzel E, Menon S, Wong C, Grimm P, Kwak C, Gallup J, McKenna KJ, Marron L, Hanna C, Tran CL, Behrendt NJ, Galan HL, Samuels J, Swinford R, Keiser AM, Rosner M, Kush ML, Nasr I, Vasu S, Boss RD, Jelin AC, Thompson RE, Davis JM, Warren DS, Hanley DF, Atkinson MA. Neonatal Survival After Serial Amnioinfusions for Anhydramnios Due to Fetal Kidney Failure: The RAFT Clinical Trial. JAMA. 2026 Jul 1:e268568. doi: 10.1001/jama.2026.8568. Online ahead of print.
- Derived from this study: PubMed 38615944Lammert DB, Miller JL, Atkinson MA, Sun LR. Single-Center Incidence and Patterns of Stroke in Early Renal Anhydramnios After Serial Amnioinfusions. J Pediatr. 2024 Aug;271:114053. doi: 10.1016/j.jpeds.2024.114053. Epub 2024 Apr 12.
- Derived from this study: PubMed 38051327Miller 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.
- Derived from this study: PubMed 35918190Atkinson 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.
- The Center for Fetal TherapyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meredith Atkinson principal investigator
Johns Hopkins University
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Serial amnioinfusions with isotonic fluid, Spinal needle and Isotonic fluid in people with Anhydramnios and Potter Syndrome, run by Johns Hopkins University at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neonates Surviving to >= 14 Days and Placement of Dialysis Access After Serial Amnioinfusions (time frame: Birth to either survival to >=14 days and placement of dialysis access, or nonsurvival, up to 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03101891, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.