Milrinone Pharmacokinetics and Acute Kidney Injury

Acute Kidney Injury Clinical Trial

— MIL-PK  

Official title:

USE OF ACUTE KIDNEY INJURY BIOMARKERS TO PREDICT IMPAIRED MILRINONE PHARMACOKINETICS IN CHILDREN FOLLOWING CARDIAC SURGERY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01966237
• Other study ID #: 2013-2507
• Status: Completed
• Start date: September 2013
• Est. completion date: July 2018

Study information

• Verified date: June 2021
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: July 2018
• Est. primary completion date: July 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Year

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases
• Wounds and Injuries

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Thrasher Research Fund

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hemodynamic parameters and AKI	Parameters of hemodynamic function defined by a decrease in central venous pressure of > 5cmH20, and/or a decrease in superior vena cava saturation by >10% at 12-36 hours after cardiopulmonary bypass. These surrogate markers of clinical outcome will be correlated with the following: operative mortality, longer time to achieve negative fluid balance, higher vasoactive inotrope score and longer intensive care and hospital length of stay.	by 72 hours
Primary	Biomarker elevation and milrinone clearance	The primary outcome variables for Aim 1 are an elevation in urinary AKI biomarkers to predict a 25% reduction in milrinone clearance.	By 24 hours
Secondary	Creatinine elevation and milrinone clearance	The secondary outcome variables for Aim 2 include a 50-75% increase in SCr to predict a 25% reduction in milrinone clearance	by 72 hours