Serial Amnioinfusions for Low Amniotic Fluid

(RAFT Trial)

Not currently recruiting at 9 trial locations

Overseen By Meredith Atkinson

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Disqualifiers: Cervical length, Congenital anomalies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for pregnant women whose fetuses have early pregnancy renal anhydramnios, a condition where the fetus lacks amniotic fluid due to kidney problems. The trial involves "serial amnioinfusions with isotonic fluid," where doctors add fluid into the womb to aid the fetus's lung development. Participants can choose between receiving these infusions or just being monitored. It is open to pregnant women diagnosed with this condition who have not chosen to terminate the pregnancy and are willing to receive care at a specialized center. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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 team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that serial amnioinfusions, which involve adding fluid into the womb, are being studied to help unborn babies with kidney problems and low amniotic fluid. These amnioinfusions can maintain normal fluid levels longer, potentially supporting lung development. This is crucial because the condition often leads to serious issues due to poor lung growth.

While the treatment aims to improve survival chances, it carries some risks. There is a significant risk of early membrane rupture and early delivery. In one study, the amnioinfusion procedure itself caused no complications, and tests for infection were negative, indicating the procedure can be safe.

However, the overall survival rate for babies born after such treatments remains low. Specifically, one study found that 82.5% of newborns did not survive. This indicates that while the procedure may benefit some unborn babies, many do not survive after birth.

These findings suggest that although serial amnioinfusions may have some risks, they are generally well-tolerated during the procedure. However, the long-term survival of these babies remains a significant challenge. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about serial amnioinfusions with isotonic fluid for low amniotic fluid because this approach offers a unique delivery method that directly addresses the issue by replenishing the fluid in the womb. Unlike standard care, which often involves monitoring and supportive measures, this method actively increases amniotic fluid levels, potentially improving outcomes for the fetus. Amnioinfusions are performed using a spinal needle, allowing for precise and repeated delivery, which could be crucial for managing conditions like fetal renal failure with anhydramnios.

What evidence suggests that this trial's treatments could be effective for early pregnancy renal anhydramnios?

This trial will compare the effects of serial amnioinfusions with isotonic fluid to expectant management. Studies have shown that repeated amnioinfusions, a procedure to add fluid to the womb, can maintain normal amniotic fluid levels longer and delay complications like early water breaking. Research indicates that restoring this fluid may support better lung development in the baby, potentially improving survival chances after birth. In one study, 82% of babies born alive after receiving this treatment met the main survival goal. These findings suggest that repeated amnioinfusions may improve outcomes for babies with conditions like early pregnancy kidney problems. However, risks such as early delivery still need consideration. ^{1 2 3 4 6}

Who Is on the Research Team?

Meredith Atkinson

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for pregnant women over 18 with a fetus diagnosed with EPRA, excluding bilateral renal agenesis. They must be before 22 weeks gestation, not planning to terminate the pregnancy, and able to start treatment before 26 weeks. Participants need to deliver at a RAFT center and agree to postnatal care there.

Inclusion Criteria

I have consulted with specialists in kidney, newborn care, transplant, surgery, pregnancy issues, social work, and genetics.

My baby has been diagnosed with renal failure, not due to missing kidneys, with no amniotic fluid before 22 weeks.

I do not plan to terminate my pregnancy.

Exclusion Criteria

Multiple gestation

I have depression that hasn't improved with treatment, confirmed by a test score.

You have signs of chorioamnionitis or abruptio placentae.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive serial amnioinfusions with isotonic fluid every 2-12 days until 26 weeks gestation

Up to 9 months

Multiple visits (in-person) for amnioinfusions

Monitoring

Participants in the expectant management group are observed serially by ultrasound, fetal echocardiogram, and MRI

Up to 9 months

Regular visits (in-person) for imaging

Follow-up

Participants are monitored for survival and placement of dialysis access after birth

Up to 3 weeks

Postnatal care at RAFT center

Long-term Follow-up

Surviving neonates are followed for up to 4 years to assess long-term outcomes and success of RAFT

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Isotonic fluid
• Serial amnioinfusions with isotonic fluid
• Spinal needle

Trial Overview The RAFT Trial tests serial amnioinfusions of isotonic fluid into the womb against standard monitoring without infusions. The goal is for the infused fluid to help fetal lung growth in cases where kidney issues have led to low amniotic fluid levels.

How Is the Trial Designed?

Group I: Serial amnioinfusions with isotonic fluid Experimental Treatment 3 Interventions

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.

Group II: Expectant Active Control 1 Intervention

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

Isotonic fluid is already approved in United States for the following indications:

Approved in United States as Isotonic fluid for:

• Experimental treatment for early pregnancy renal anhydramnios (EPRA)

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Amnioinfusion during labor in patients with chorioamnionitis was associated with a significant reduction in maternal temperature at delivery (99.8°F vs. 100.5°F), suggesting it may help manage febrile morbidity in these cases.

The study, which included 34 patients, found no significant differences in postpartum endometritis rates or neonatal infections between the amnioinfusion and control groups, indicating that amnioinfusion is safe and does not increase infection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic amnioinfusion in preganancies complicated by chorioamnionitis: a prospective randomized trial. Parilla, BV., McDermott, TM.[2015]

Amnioinfusion with normal saline significantly increases fetal plasma sodium and chloride concentrations, leading to a slight decrease in fetal arterial pH, indicating a hyperchloremic acidosis, while lactated Ringer's solution causes minimal changes.

The study involved chronically catheterized fetal sheep (n=28) and demonstrated that normal saline infusion can alter fetal electrolyte levels and acid-base balance, but these changes remain within a physiologic range, suggesting safety in the use of saline for amnioinfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal electrolyte and acid-base responses to amnioinfusion: lactated Ringer's versus normal saline in the ovine fetus. Shields, LE., Moore, TR., Brace, RA.[2019]

In a study involving 30 laboring women with oligohydramnios, a 250 ml amnioinfusion of normal saline significantly increased the amniotic fluid index by an average of 4.3 cm, demonstrating its efficacy in managing low amniotic fluid levels.

The results suggest that amnioinfusion is a safe and effective intervention for improving amniotic fluid volume in pregnant women at or beyond 37 weeks' gestation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic fluid volume increase after amnioinfusion of a fixed volume. Strong, TH., Hetzler, G., Paul, RH.[2019]

In a study of 305 patients with oligohydramnios, prophylactic amnioinfusion significantly reduced the need for operative interventions due to fetal distress and lowered the cesarean section rate, indicating its efficacy in improving labor outcomes.

Patients who received amnioinfusion also had higher umbilical artery pH levels at delivery and shorter hospital stays, suggesting that this intervention can enhance fetal well-being without increasing the risk of complications like amnionitis or endometritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic amnioinfusion as a treatment for oligohydramnios in laboring patients: a prospective, randomized trial. Schrimmer, DB., Macri, CJ., Paul, RH.[2019]

In a study of 84 pregnant women with low amniotic fluid, hydration with intravenous hypotonic fluid or oral water significantly increased the amniotic fluid index (AFI), while isotonic fluid did not show a similar effect.

The increase in AFI was more closely related to changes in maternal osmolality rather than just the volume of fluid given, suggesting that osmotic changes play a key role in improving amniotic fluid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods. Doi, S., Osada, H., Seki, K., et al.[2019]

In a study of 100 patients with various pregnancy complications, saline solution amnioinfusion significantly reduced the incidence of postpartum endometritis (2.4% vs 19%) and showed a trend towards lower cesarean deliveries due to fetal distress (4.7% vs 16%).

Amnioinfusion also improved the estimation of amniotic fluid volume, with a significant increase in the four-quadrant ultrasound measurement (14.7 cm vs 9.8 cm), indicating its potential efficacy in managing complications related to amniotic fluid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective randomized study of saline solution amnioinfusion. Owen, J., Henson, BV., Hauth, JC.[2019]

In a study of 53 patients with low amniotic fluid (AFI ≤ 5.0 cm), prophylactic saline amnioinfusion did not significantly reduce adverse fetal outcomes compared to a control group, despite increasing the AFI from 3.0 cm to 8.9 cm after treatment.

There were no significant differences in the rates of complications such as fetal heart rate decelerations, need for cesarean sections, or low Apgar scores between the amnioinfused group and the non-infused group, suggesting that amnioinfusion may not provide the expected benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic intrapartum amnioinfusion for patients with oligohydramnios. A prospective randomized study. Chauhan, SP., Rutherford, SE., Hess, LW., et al.[2004]

Two cases of fatal amniotic fluid embolism occurred in women who underwent saline amnioinfusion during labor, particularly after thick meconium staining was observed, raising concerns about the safety of this intervention in such situations.

While amniotic fluid embolism is rare, the cases suggest a potential link between amnioinfusion and increased risk, especially in the presence of rapid labor and meconium-stained fluid, warranting further investigation without immediate changes to clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic fluid embolism after saline amnioinfusion: two cases and review of the literature. Maher, JE., Wenstrom, KD., Hauth, JC., et al.[2015]

Amnioinfusion, a procedure where saline is infused into the amniotic cavity, has shown promising results in reducing fetal heart rate decelerations and complications like low Apgar scores and the need for cesarean sections, based on several small randomized trials.

While amnioinfusion appears beneficial for conditions like oligohydramnios and thick meconium-staining, larger trials are necessary to fully understand its impact on perinatal mortality and potential complications such as umbilical cord prolapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amnioinfusion. Hofmeyr, GJ., Gulmezoglu, AM., Nikodem, VC., et al.[2019]

Amnioinfusion, a technique where saline is infused into the amniotic sacs, was successfully performed in three cases of twin pregnancies with low amniotic fluid (oligohydramnios), leading to safe vaginal deliveries.

No adverse effects were reported from the procedure, and follow-up ultrasounds are recommended to monitor the increase in amniotic fluid volume after the infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapartum amnioinfusion in twin gestation. A preliminary report of three cases. Strong, TH., Howard, MW., Wade, BK., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11628636/

Comparison of Serial Amnioinfusion Strategies for Isolated ... Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2542454820300734

Review Serial Amnioinfusion as Regenerative Therapy ... The aim of this study was to investigate the effect of serial amnioinfusion therapy (SAT) for pulmonary hypoplasia in lower urinary tract obstruction (LUTO) ...

3. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.6850

Serial Amnioinfusion Therapy for Treatment of Congenital ... Overall neonatal mortality was 82.5% (33 of 40). These findings suggest that SAT for BRA improves the chances of neonatal survival in the first ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2812481

Neonatal Survival After Serial Amnioinfusions for Bilateral ... Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38051327/

The Renal Anhydramnios Fetal Therapy Trial - PubMed - NIH The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06728228?term=AREA%5BConditionSearch%5D(Multicystic%20dysplastic%20kidney%20OR%20%22MCDK%22%20OR%20%22%20multicystic%20renal%20dysplasia%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=1

NCT06728228 | Amnioinfusion for Fetal Renal Failure 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 ...