Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage

NCT ID: NCT05853601

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-17
• Study Completion Date: 2027-04-01

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Single Dose Theophylline

Single dose of theophylline or aminophylline (5mg/kg IV) given within 18 hours after birth

Group Type: EXPERIMENTAL

Single Dose Theophylline

Intervention Type: DRUG

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.

Repeat Dose Theophylline

Loading dose of theophylline or aminophylline (5mg/kg IV) given within 18 hours of birth, with two subsequent doses (1.2 mg/kg IV) given at 12 and 24 hours after the loading dose

Group Type: EXPERIMENTAL

Repeat Dose Theophylline

Intervention Type: DRUG

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.

Standard treatment

Infants cared for according to standard practice.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• gestational age at birth >= 35 weeks by best obstetrical dating
• birth weight > 1800 grams
• clinical determination of HIE and treatment with hypothermia being initiated within six hours of birth according to institutional guidelines
• no known congenital abnormalities involving the brain, kidneys, heart or lungs
• ability to administer theophylline via intravenous route within 18 hours of birth

Exclusion Criteria

• infants with suspected or diagnosed significant renal, urinary tract, brain, heart, or lung abnormalities
• infant with known chromosomal anomaly
• evidence of head trauma or skull fracture causing major intracranial hemorrhage
• inability to initiate hypothermia within six hours of birth
• attending physician unwilling to have infant participate in the study
• inability to obtain informed consent within 18 hours of birth

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 18 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oklahoma

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Segar

Professor, Department of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Segar, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jeffrey Segar, MD

Role: CONTACT

jsegar@mcw.edu

414-955-8296

Elizabeth Awe, BA

Role: CONTACT

eawe@childrenswi.org

414-266-6560

Facility Contacts

Birju Shah, MD

Role: primary

birju-shah@ouhsc.edu

405-271-5215

Natalie Goodman, BA

Role: backup

Natalie-Goodman@ouhsc.edu

405-271-5215 ext. 43006

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Other Identifiers

PRO46949

Identifier Type: -

Identifier Source: org_study_id