Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage (TheoPHyLNNe)

April 8, 2026 updated by: Jeffrey Segar, Medical College of Wisconsin
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jeffrey Segar, MD
  • Phone Number: 414-955-8296
  • Email: jsegar@mcw.edu

Study Contact Backup

Study Locations

  • United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard treatment
Infants cared for according to standard practice.
Experimental: Single Dose Theophylline
Single dose of theophylline or aminophylline (5mg/kg IV) given within 18 hours after birth
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.
Experimental: 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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment of patients
Time Frame: 2 years
Examine the ability to recruit and enroll patients in trial. We will assess the number of eligible patients and compare that number to those actually enrolled. This ratio will inform regarding the ability to recruit patients in a larger, randomized, appropriately powered trial.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic Profile of Theophylline#1
Time Frame: 2 years
Evaluate plasma concentrations (mg/dl) of theophylline at time points ranging from 30 minutes to 48 hours after dosing
2 years
Safety profile of theophylline#2
Time Frame: 2 years
Incidence of hyperglycemia, defined as two sequential serum glucose values over 200 mg/dl) over one hour apart after theophylline dosing
2 years
Safety profile of theophylline#3
Time Frame: 2 years
Incidence of clinical seizures as diagnosed by a trained pediatric neurologist
2 years
Demonstration of successful adherence to study protocol
Time Frame: 2 years
Evaluate the incidence of protocol deviations both per subject and study-wide. Incidence will be expressed as number of study violations per enrolled subject
2 years
Successful data collection procedures
Time Frame: 2 years
Percent of incomplete data entry points per subject will be evaluated by reviewing data in REDCap
2 years
Pharmacokinetic Profile of Theophylline#2
Time Frame: 2 years
Determine area under the curve profile of serum theophylline concentration (mg/dl) over time (hours) up to 48 hours after dosing of theophylline
2 years
Acute kidney injury#1
Time Frame: 2 years
Incidence of acute kidney injury as defined by modified neonatal KDIGO criteria using serum creatinine values
2 years
Acute kidney injury#2
Time Frame: 2 years
Incidence of acute kidney injury as defined by modified neonatal KDIGO criteria using urine output values (ml/kg/hour)
2 years
Safety profile of theophylline#1
Time Frame: 2 years
Incidence of tachycardia (heart rate > 200 beats per minute for 15 minutes) after theophylline dosing defined by pediatric neurologist
2 years
Successful biospecimen collection procedures
Time Frame: 2 years
Rate of successful collection and analysis of biospecimens per study logs. Data will be determined as percentage of successful completions (successful completions divided by opportunities per protocol).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical College of Wisconsin

Collaborators

University of Oklahoma

Investigators

  • Principal Investigator: Jeffrey Segar, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2023

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

November 1, 2027

Study Registration Dates

First Submitted

March 20, 2023

First Submitted That Met QC Criteria

May 2, 2023

First Posted (Actual)

May 11, 2023

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 8, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO46949

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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