Clinical trial NCT01966237: Milrinone Pharmacokinetics and Acute Kidney Injury
Official title: USE OF ACUTE KIDNEY INJURY BIOMARKERS TO PREDICT IMPAIRED MILRINONE PHARMACOKINETICS IN CHILDREN FOLLOWING CARDIAC SURGERY
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Acute Kidney Injury
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2013-10-21
Enrollment: 92
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients less than or equal to 1 year who present for cardiac surgery at Cincinnati Children's Hospital Medical Center who meet the eligibility criteria.

Brief summary: Acute kidney injury (AKI) occurs in 40% of children following heart surgery. Serum creatinine (Scr) is a late biomarker of AKI, rising 24-48 hours after surgery. Thus, for medicines excreted in the urine, AKI could potentially lead to toxic levels in the blood. Urinary biomarkers have the ability to detect AKI earlier. Whether early detection of AKI through urinary biomarkers can predict altered drug levels is unknown.

Milrinone is used to improve heart function after surgery, but accumulates in AKI resulting in low blood pressure. Dose adjustments are not currently possible because of the late rise in SCr, and are based on clinical parameters that may lead to clinically relevant over or under-dosing. Thus, this study will address an important knowledge gap being the first to use elevations of AKI biomarker concentrations to anticipate increased milrinone levels.


Eligibility criteria: Inclusion Criteria:

* Undergoing cardiothoracic surgery with cardiopulmonary bypass
* weight greater than 2500 grams (5 pounds 8 ounces) at the time of surgery
* gestational age \> 36 weeks
* age less \< to 1 year
* infants with complex congenital heart disease
* use of milrinone in the intra-operative and post-operative period.

Exclusion Criteria:

* Pre-existing kidney disease (structural and functional abnormalities) as determined by the Principal Investigator
* use of aminoglycosides within 48 hours of planned surgery
* cardiac arrest prior to cardiac surgery
* extracorporeal membrane oxygenation prior to cardiac surgery
* urinary tract infection prior to surgery
* repair of an isolated atrial or ventricular septal defect

Primary outcomes:
measure: Biomarker elevation and milrinone clearance
timeFrame: By 24 hours
Secondary outcomes:
measure: Creatinine elevation and milrinone clearance
timeFrame: by 72 hours
Other outcomes:
measure: Hemodynamic parameters and AKI
timeFrame: by 72 hours
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: University of Colorado, Denver
name: Katja M Gist, DO, MSCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mizuno T, Gist KM, Gao Z, Wempe MF, Alten J, Cooper DS, Goldstein SL, Vinks AA. Developmental Pharmacokinetics and Age-Appropriate Dosing Design of Milrinone in Neonates and Infants with Acute Kidney Injury Following Cardiac Surgery. Clin Pharmacokinet. 2019 Jun;58(6):793-803. doi: 10.1007/s40262-018-0729-3.
citation: Gist KM, Cooper DS, Wrona J, Faubel S, Altmann C, Gao Z, Marino BS, Alten J, Hock KM, Mizuno T, Vinks AA, Joy MS, Wempe MF, Bennett MR, Goldstein SL. Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine-Defined Acute Kidney Injury in Infants After Cardiac Surgery. Ther Drug Monit. 2018 Apr;40(2):186-194. doi: 10.1097/FTD.0000000000000496.
citation: Gist KM, Goldstein SL, Wrona J, Alten JA, Basu RK, Cooper DS, Soranno DE, Duplantis J, Altmann C, Gao Z, Faubel S. Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery. Pediatr Nephrol. 2017 Sep;32(9):1611-1619. doi: 10.1007/s00467-017-3655-y. Epub 2017 Apr 5.