Milrinone Pharmacokinetics and Acute Kidney Injury

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01966237

Acronym

MIL-PK

Enrollment

Registered

2013-10-21

Start date

2013-09-30

Completion date

2018-07-31

Last updated

2021-06-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Kidney Injury, Congenital Heart Disease

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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

1 Days to 1 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Other

Measure	Time frame	Description
Hemodynamic parameters and AKI	by 72 hours	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.

Countries

United States

Outcome results