Milrinone Pharmacokinetics and Acute Kidney Injury

NCT01966237 | Completed

• 1 other identifier: 2013-2507
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Heart Disease; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Creatinine elevation and milrinone clearance

  by 72 hours

Other Outcomes (1)

• Hemodynamic parameters and AKI

  by 72 hours

Study Arms (2)

Acute kidney injury

AKI defined by an elevation in urinary AKI biomarkers

No acute kidney injury

No AKI defined by normal urinary AKI biomarkers

Eligibility Criteria

• Age: 1 Day - 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Thrasher Research Fund: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (3)

• 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.

  PMID: 30607889 DERIVED

• 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.

  PMID: 29529007 DERIVED

• 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.

  PMID: 28382566 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Katja M Gist, DO, MSCS

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 21, 2013
• Study Start: September 1, 2013
• Primary Completion: July 31, 2017
• Study Completion: July 1, 2018
• Last Updated: June 22, 2021

Record last verified: 2021-06

Locations

US (1)