Amnioinfusion for Intrauterine Neuroprotection

NCT ID: NCT05513690

Last Updated: 2022-08-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-15
• Study Completion Date: 2024-07-01

Brief Summary

Hypoxic ischemic encephalopathy (HIE), a serious brain injury in infants, occurs in 2-9 per 1,000 infants after delivery. Up to 60% of infants diagnosed with HIE die and 25% of the survivors have long-term neurologic deficits. Risk factors for HIE include abnormal fetal heart tracings and intrauterine infection. Therapeutic whole-body cooling of infants with HIE is standard of care after delivery, with only 7-9 at-risk infants needing to be treated to prevent one infant from suffering long-term neurologic deficits. However, animal studies show that therapeutic cooling may be more beneficial when given in utero at the time of an insult, rather than after delivery. Though therapeutic cooling in utero has yet to be explored in humans, an established in utero fluid delivery system during labor-amnioinfusion-provides a unique opportunity for in utero intervention. We propose a pilot randomized controlled trial to test the feasibility and preliminary effects of room temperature amnioinfusion on tissue injury including HIE.

Detailed Description

Hypoxic ischemic encephalopathy (HIE), a serious brain injury in infants, occurs in 2-9 per 1,000 infants after delivery. Up to 60% of infants diagnosed with HIE die and 25% of the survivors have long-term neurologic deficits. Risk factors for HIE include abnormal fetal heart tracings and intrauterine infection. In addition, maternal fever is associated with a four to five-fold increased risk of HIE. Two phases leading to HIE are recognized: neuronal death from cellular hypoxia and further injury from exhaustion of energy stores.

Therapeutic cooling of infants with HIE provides neuroprotection by reducing metabolic demands and suppressing toxic processes. Studies show that whole-body cooling of infants reduces the risk of neurologic motor and cognitive deficits with brain imaging suggesting that human infants who are cooled earlier have a greater benefit. Moreover, animal studies show that brain cooling may be more beneficial when given in utero at the time of an insult during the first phase of cellular hypoxia, rather than after delivery. Though therapeutic cooling in utero has yet to be explored in humans, an established in utero fluid delivery system-amnioinfusion- provides a unique opportunity for in utero intervention.

Amnioinfusion (AI), the administration of fluid via an intrauterine catheter inserted through the cervix, is a common intervention during labor to improve fetal heart tracings and reduce cesarean delivery. Introduced in 1983, it used warm saline due to a theoretical concern for fetal shock from cold fluids. Subsequent studies showed no advantage of warm fluids, and fluids at room temperature (~25oC) have become standard. AI can lower in utero temperature by 1.0°C (36.4°C versus 37.4°C, P<0.01). This 1.0°C degree of cooling has been associated a 6% reduction in brain energy utilization which could be protective against neurological injury. This suggests that AI can be leveraged to lower in utero and fetal temperatures to protect against neurologic injury.

Expanding the indication for AI is a novel approach to reduce neurologic injury in utero. However, there is a gap in the acceptability and efficacy of amnioinfusion for this indication. To fill this gap, we propose a pilot randomized controlled trial to test the feasibility and effects of amnioinfusion with fluids at room temperature on infants at high risk for neurologic injury including HIE.

Conditions

Lactic Acidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Amnioinfusion at room temperature (intervention arm)

Routine amnioinfusion will be administered via an intrauterine catheter inserted through the cervix. Normal saline at room temperature will be infused per hospital protocol at a rate of 600 milliliters/hour for the first hour followed by 180 milliliters/hour. A plastic applicator will be used to introduce a flexible disposable general-purpose temperature probe into the uterus. The probe will be guided to the contralateral side of the uterus from the intrauterine pressure catheter. Intrauterine temperature will then be measured by DataThermII continuous temperature monitor. This monitor has accuracy of 0.1 °C and will store temperature measurements every 10 minutes until delivery. The temperature data will be downloaded into a computer software. The DataThermII has been previously used in prior research to measure intrauterine temperature.

Group Type: EXPERIMENTAL

Amnioinfusion at room temperature (intervention arm)

Intervention Type: PROCEDURE

Routine amnioinfusion and intrauterine temperature probe sensor

Standard of care (control arm)

Women in this group will have the temperature probe placed and temperate measured as described in experimental arm. They will otherwise receive current standard of care (i.e. no amnioinfusion).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Amnioinfusion at room temperature (intervention arm)

Routine amnioinfusion and intrauterine temperature probe sensor

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Maternal age >18 years old
• Singleton
• Term gestational age at time of admission (>37 weeks 0 days);

Exclusion Criteria

• Major fetal anomaly
• Active substance or alcohol use
• Contraindications to intrauterine pressure catheter placement (e.g. placental previa, human immunodeficiency virus, Hepatitis C)
• Fetal growth restriction
• Inability to consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Foundation for Society of Maternal-Fetal Medicine

UNKNOWN

Sponsor Role: collaborator

Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brock Polnaszek, MD

Role: PRINCIPAL_INVESTIGATOR

Waren Alpert Medical School of Brown University, Women and Infant's Hospital

Locations

Women and Infant's Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sue Elmore, MS,CRRP

Role: CONTACT

selmore@carene.org

401-274-1122 ext. 48675

Facility Contacts

Brock Polnaszek, MD

Role: primary

Other Identifiers

WIHRI

Identifier Type: -

Identifier Source: org_study_id