Serial Amnioinfusions for Low Amniotic Fluid

(RAFT Trial)

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

70 Participants Needed

Trial Summary

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.

What data supports the idea that Serial Amnioinfusions for Low Amniotic Fluid is an effective treatment?

The available research shows that Serial Amnioinfusions for Low Amniotic Fluid can be effective. In one study, patients who received amnioinfusion had fewer cesarean sections due to fetal distress compared to those who did not receive the treatment (4.7% vs 16%). Another study found that patients receiving amnioinfusion had significantly less need for surgical intervention and fewer cesarean sections. Additionally, the amniotic fluid volume increased significantly after the treatment, which is beneficial for the pregnancy. These findings suggest that Serial Amnioinfusions can improve outcomes for both the mother and the baby. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Serial Amnioinfusions for Low Amniotic Fluid?

Research shows that amnioinfusion, which involves adding fluid into the amniotic sac, can significantly reduce the need for cesarean sections and improve the condition of the baby at birth in cases of low amniotic fluid. It also increases the amount of amniotic fluid, which can help improve outcomes for both mother and baby. ^{1 2 3 4 5}

What safety data exists for serial amnioinfusions for low amniotic fluid?

The safety data for amnioinfusion, including serial amnioinfusions, suggests it is generally safe with few adverse effects. Studies have shown benefits such as reduced postpartum endometritis, decreased cesarean delivery rates due to fetal distress, and improved amniotic fluid volume. No significant untoward effects were identified in trials, and it was associated with decreased intrapartum morbidity. However, rare cases of amniotic fluid embolism have been reported, indicating the need for further research. ^{1 3 6 7 8}

Is serial amnioinfusion generally safe for humans?

Amnioinfusion is generally considered safe with few adverse effects, and studies have shown it can reduce certain complications during labor without significant negative outcomes for mothers or babies. ^{1 3 6 7 8}

Is the treatment Serial amnioinfusions with isotonic fluid a promising treatment for low amniotic fluid?

Yes, Serial amnioinfusions with isotonic fluid is a promising treatment for low amniotic fluid. Studies show it can reduce the need for cesarean sections, improve the baby's condition at birth, and decrease the mother's hospital stay. It also helps increase the amount of amniotic fluid, which is important for the baby's health. ^{1 2 3 9 10}

How does the treatment of serial amnioinfusions with isotonic fluid for low amniotic fluid differ from other treatments?

Serial amnioinfusions with isotonic fluid are unique because they involve directly infusing a sterile fluid with balanced electrolytes into the amniotic sac to increase the amniotic fluid volume, which can help reduce complications during labor and delivery. This method is different from other treatments as it directly addresses the low fluid issue by replenishing it, potentially reducing the need for cesarean sections and improving fetal hydration. ^{1 2 3 9 11}

What is the purpose of this trial?

This trial tests a method of injecting fluid into the womb of pregnant women whose fetuses have a severe kidney condition that prevents normal lung development. The goal is to help the fetus's lungs grow so they can survive after birth. The trial focuses on the safety and effectiveness of this treatment for fetuses with urinary tract issues.

Research Team

Meredith Atkinson

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prophylactic amnioinfusion as a treatment for oligohydramnios in laboring patients: a prospective, randomized trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Prophylactic intrapartum amnioinfusion for patients with oligohydramnios. A prospective randomized study. [2004]

3. United States pubmed.ncbi.nlm.nih.gov

A prospective randomized study of saline solution amnioinfusion. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Amniotic fluid volume increase after amnioinfusion of a fixed volume. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Amniotic fluid embolism after saline amnioinfusion: two cases and review of the literature. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Prophylactic amnioinfusion in preganancies complicated by chorioamnionitis: a prospective randomized trial. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Fetal electrolyte and acid-base responses to amnioinfusion: lactated Ringer's versus normal saline in the ovine fetus. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Intrapartum amnioinfusion in twin gestation. A preliminary report of three cases. [2015]

10. Ireland pubmed.ncbi.nlm.nih.gov

Amnioinfusion. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Increase in fetal hydration during long-term intraamniotic isotonic saline infusion. [2019]