NCT05853601

Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 1 Hour – 18 Hours
• Healthy volunteers: Not accepted

Summary

Acute kidney injury is a significant complication for infants who experience hypoxic ischemic encephalopathy, being associated with increased rates of death and prolonged hospitalization. This pilot study of theophylline administration soon after birth for the prevention of kidney injury will lay the foundation for the conduct of a larger clinical trial that seeks to identify a theophylline as a novel therapy to prevent kidney injury in thousands of at-risk infants.

Detailed description

Acute kidney injury (AKI) is commonly seen in infants diagnosed with hypoxic-ischemic encephalopathy (HIE) and is associated with increased rates of morbidity and mortality. Currently, there are no approved therapies that target the prevention of AKI. Several small trials in infants with HIE suggest that a single dose of theophylline given soon after birth attenuates the development of AKI. However, these studies were not performed in infants being treated with therapeutic hypothermia (the current standard of care for moderate to severe HIE), and only reported short-term outcomes. Therefore, few clinicians use theophylline in the management of these patients. The long-term goal is to undertake an appropriately powered multicenter clinical trial to test the hypothesis that for infants \> 35 weeks gestation treated with therapeutic hypothermia for HIE, intravenous theophylline (or aminophylline) within the first 18 hours after birth will result in a decreased incidence and/or severity of AKI or death (composite primary outcome) and improved long-term (2 year) renal outcomes. Before the conduct of a large trial, the feasibility of implementing the intervention and ability to measure relevant clinical outcomes need to be demonstrated. Therefore, the investigators propose a small pilot and feasibility clinical trial to i) evaluate recruitment, protocol adherence, and data collection procedures in a therapeutic trial of theophylline to decrease the incidence of AKI or death compared to standard treatment in infants with HIE being treated with therapeutic hypothermia; ii) evaluate the utility and applicability of established measures (serum creatinine, urine output, fluid balance) and novel, exploratory approaches to identify AKI in infants; and iii) determine theophylline pharmacokinetic, pharmacodynamic, safety and preliminary effectiveness profiles of two different theophylline dosing regimens in a therapeutic trial of theophylline to decrease the incidence of AKI or death compared to standard treatment. Using a mixed methods data analysis strategy to assess the research and intervention process and examine outcomes of the intervention, the investigators will generate the requisite data to inform development and implementation of an appropriately powered study to determine whether theophylline attenuates the risk and severity of AKI in infants with HIE treated with therapeutic hypothermia.

Conditions

• Acute Kidney Injury
• HIE

Interventions

Type	Name	Description
DRUG	Single Dose Theophylline	Subjects are given a single loading dose of theophylline, 5mg/kg IV, within 18 hours after birth. A bioequivalent dose of aminophylline, a more soluble, ethylenediamine salt of theophylline, may be substituted for theophylline. The bioequivalent dose of aminophylline is 120% of the theophylline dose.
DRUG	Repeat Dose Theophylline	Subjects are given a loading dose of theophylline, 5mg/kg IV, within 18 hours of birth, and then two subsequent doses (1.2mg/kg iv) at 12 hours and 24 hours after loading dose. A bioequivalent dose of aminophylline, a more soluble, ethylenediamine salt of theophylline, may be substituted for theophylline. The bioequivalent dose of aminophylline is 120% of the theophylline dose.

Timeline

• Start date: 2023-10-17
• Primary completion: 2026-11-01
• Completion: 2027-11-01
• First posted: 2023-05-11
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study