Clinical trial NCT05853601: Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage
Official title: Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Kidney Injury
HIE
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: University of Oklahoma
First posted: 2023-05-11
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Recruitment of patients
timeFrame: 2 years
Secondary outcomes:
measure: Pharmacokinetic Profile of Theophylline#1
timeFrame: 2 years
measure: Safety profile of theophylline#1
timeFrame: 2 years
measure: Safety profile of theophylline#2
timeFrame: 2 years
measure: Safety profile of theophylline#3
timeFrame: 2 years
measure: Demonstration of successful adherence to study protocol
timeFrame: 2 years
measure: Successful data collection procedures
timeFrame: 2 years
measure: Successful biospecimen collection procedures
timeFrame: 2 years
measure: Pharmacokinetic Profile of Theophylline#2
timeFrame: 2 years
measure: Acute kidney injury#1
timeFrame: 2 years
measure: Acute kidney injury#2
timeFrame: 2 years
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: Medical College of Wisconsin
name: Jeffrey Segar, MD
role: PRINCIPAL_INVESTIGATOR
References: