Kidney Injury, Pre-Term
Conditions
Keywords
caffeine, acute kidney injury
Brief summary
This study is being done to see if additional caffeine citrate (20 milligrams per kilogram IV bolus) helps babies with low kidney oxygenation already being treated with caffeine citrate (20 milligrams per kilogram IV bolus on day of life (DOL) 1 followed by 8 milligrams per kilogram daily maintenance). The investigators hypothesize that additional caffeine will improve kidney oxygen levels, while not causing any brain injury, and may reduce rates of acute kidney injury compared to placebo. This study will take place in preterm babies born less than 30 weeks gestational age, with the intervention occurring between greater than 48 hours of age until DOL 14 and outcomes tracked until neonatal intensive care unit (NICU) discharge.
Detailed description
The study population will consist of 114 preterm neonates born less than 30 weeks gestational age who have an intravenous (IV) line for which IV medications can be administered and who can have brain and kidney Near Infrared Spectroscopy (NIRS) monitoring. Eligible participants will be enrolled between 12-96 hours of life after preterm birth and admission to the Meriter NICU. Baseline data will be collected and NIRS monitoring will be started when appropriate as determined by the team based on clinical guidelines and standard of care. Those participants having kidney oxygenation less than 50 percent (and troubleshooting procedures have occurred and while ensuring brain oxygenation is not below 55 percent) after 48 hours and within the first 14 DOL will be randomized in a 1:1 manner to one of two treatment arms (Arm 1 and Arm 2). * Arm 1: IV caffeine citrate (20 mg/kg) (n = 51) * Arm 2: Placebo - same volume of 0.9% Sodium Chloride United States Pharmacopeia (USP) (n=51) Those participants who do not develop kidney hypoxia during the first 14 DOL will be the normal kidney oxygenation control group and receive no intervention (Arm 3). * Arm 3: Normal Kidney oxygenation (no intervention) (Approximately n = 12) Participant accrual will occur over 48 months. Participants will complete all study specific activities during the NICU hospitalization over the course of the first 28 DOL and clinical outcomes will be collected through NICU discharge or 6 months of age, whichever occurs first. Each participant will contribute blood specimens for creatinine and caffeine levels as well as approximately 20-40 urine samples for biomarker analysis.
Interventions
DRUGCaffeine citrate
intravenous (IV) caffeine citrate (20 milligrams per kilogram) followed by 8 milligrams per kilogram daily maintenance
DRUGPlacebo
same volume of 0.9 percent Sodium Chloride United States Pharmacopeia (USP)
Sponsors
University of Wisconsin, Madison
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
This is a randomized, placebo-controlled, double blind, single-center trial of the effectiveness of additional caffeine compared to placebo in preterm neonates less than 30 weeks gestational age. Multiples will be randomized to the same arm of the study, the first born will be randomized to determine arm.
Eligibility
Sex/Gender
ALL
Age
12 Years to 96 Years
Healthy volunteers
No
Inclusion criteria
* Gestational age at birth between 23 0/7 and 29 6/7 weeks. * Able to have near-infrared spectroscopy (NIRS) monitoring of cerebral and kidney oxygenation. * Able to receive IV medications. * Indwelling umbilical arterial catheter (UAC), umbilical venous catheter (UVC), peripheral arterial line (PAL), or peripherally inserted central catheter (PICC) already in place that can draw blood. * Receiving caffeine at the time of enrollment * Have a birth parent who is at least 18 years old and have a parent or guardian who is able to provide parental permission in English or Spanish
Exclusion criteria
* Known or suspected major congenital anomaly of the brain, heart, lungs or kidney (excluding UTD A1 pyelectasis). * Known or suspected chromosomal or genetic anomaly. * Not suitable for study participation due to other reasons at the discretion of the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants with Improvement in Kidney Oxygenation | Up to 3 hours post-intervention (Between days 1 and 17) | In the 3 hours after receiving the intervention or placebo, participants have kidney oxygenation monitored. Improvement in oxygenation is defined as having 30 minutes where at least 90 percent of measured values are at least 50 percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days of Acute Kidney Injury (AKI) | 14 days after intervention | AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) foundation. Outcome is measured for the 14 days after intervention. |
| Proportion of Participants with a Sustained Decrease in Cerebral Oxygenation | up to 3 hours post-intervention (Between days 1 and 17) | In the 3 hours after receiving the intervention or placebo, participants have cerebral oxygenation monitored. A sustained decrease in cerebral oxygenation is defined as less than 60 percent oxygenation for at least 60 minutes. |
Countries
United States
Contacts
CONTACTElena Alfaro, CCRP
PRINCIPAL_INVESTIGATORMatthew W Harer, MD
UW School of Medicine and Public Health
Outcome results
None listed