Congenital Heart DiseaseMIL-PKNCT01966237
Milrinone Pharmacokinetics and Acute Kidney Injury
An observational study of Congenital Heart Disease and Acute Kidney Injury, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 1 day to 1 year
- Conditions the study is for
- Congenital Heart Disease, Acute Kidney Injury
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Jul 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 1 year
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: USE OF ACUTE KIDNEY INJURY BIOMARKERS TO PREDICT IMPAIRED MILRINONE PHARMACOKINETICS IN CHILDREN FOLLOWING CARDIAC SURGERY
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
- Medical subject headings
- Heart Defects, Congenital, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Acute kidney injury | AKI defined by an elevation in urinary AKI biomarkers | |
| No acute kidney injury | No AKI defined by normal urinary AKI biomarkers |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: By 24 hours
Secondary outcomes (1)
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
Measured: by 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2013 (estimated)
- Study startSep 2013
- Primary completion31 Jul 2017
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Sponsor
- Investigators
- Katja M Gist, DO, MSCS, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966237
- Sponsor's protocol ID
- 2013-2507
- Acronym
- MIL-PK
- Status last verified
- Jun 2021
- First submitted
- 17 Oct 2013
- Last updated
- 22 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30607889Gist 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.
PubMed 29529007Gist 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.
PubMed 28382566
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- USE OF ACUTE KIDNEY INJURY BIOMARKERS TO PREDICT IMPAIRED MILRINONE PHARMACOKINETICS IN CHILDREN FOLLOWING CARDIAC SURGERY
- ClinicalTrials.gov ID
- NCT01966237
- Acronym / sponsor ID
- MIL-PK / 2013-2507
- Conditions
- Congenital Heart Disease, Acute Kidney Injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- Sep 2013
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 21 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute kidney injury | – | –AKI defined by an elevation in urinary AKI biomarkers |
| No acute kidney injury | – | –No AKI defined by normal urinary AKI biomarkers |
Who may qualify
- Ages
- 1 day to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Biomarker elevation and milrinone clearance
Time frame: 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.
1 secondary outcome
Creatinine elevation and milrinone clearance
Time frame: by 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- Derived from this study: PubMed 30607889Mizuno 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.
- Derived from this study: PubMed 29529007Gist 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.
- Derived from this study: PubMed 28382566Gist 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katja M Gist, DO, MSCS principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Heart Disease and Acute Kidney Injury, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker elevation and milrinone clearance (time frame: By 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01966237, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.