Milrinone Pharmacokinetics and Acute Kidney Injury

Completed

• Conditions: Congenital Heart Disease; Acute Kidney Injury

• Registration Number: NCT01966237
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-10-17
• Study First Submitted QC: 2013-10-17
• Study First Posted: 2013-10-21
• Primary Completion: 2017-07-31
• Study Completion: 2018-07
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-17
• Last Update Posted: 2021-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Biomarker elevation and milrinone clearance	By 24 hours	The primary outcome variables for Aim 1 are an elevation in urinary AKI biomarkers to predict a 25% reduction in milrinone clearance.

Secondary Outcome Measures

Name	Time	Method
Creatinine elevation and milrinone clearance	by 72 hours	The secondary outcome variables for Aim 2 include a 50-75% increase in SCr to predict a 25% reduction in milrinone clearance

Trial Locations

Locations (1)

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States