Milrinone Pharmacokinetics and Acute Kidney Injury

NCT ID: NCT01966237

Last Updated: 2021-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

92 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-09-30

Study Completion Date

2018-07-31

Brief Summary

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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

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Conditions

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Congenital Heart Disease Acute Kidney Injury

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Acute kidney injury

AKI defined by an elevation in urinary AKI biomarkers

No interventions assigned to this group

No acute kidney injury

No AKI defined by normal urinary AKI biomarkers

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

1 Day

Maximum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Thrasher Research Fund

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katja M Gist, DO, MSCS

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 30607889 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29529007 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28382566 (View on PubMed)

Other Identifiers

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2013-2507

Identifier Type: -

Identifier Source: org_study_id

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