Back to resultsDeferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury (DEFEAT-AKI)
Primary Purpose
Acute Kidney Injury
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Deferoxamine
Normal saline
Sponsored by
About this trial
This is an interventional prevention trial for Acute Kidney Injury
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years
- Undergoing coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass
- AKI risk score ≥6 at the time of screening
- Written informed consent from the patient or surrogate
Exclusion Criteria:
AKI, defined as any of the following:
- Increase in serum creatinine ≥0.3 mg/dl in 48h
- Increase in serum creatinine ≥50% in 7d (if no value available in last 7d, use most recent value in last 3 months)
- Urine output ≤0.5 ml/kg/h x 6 consecutive hours (only assessed in patients with hourly monitoring via Foley catheter)
- Receipt of renal replacement therapy (RRT) within 7d
- Advanced chronic kidney disease (eGFR <15 ml/min/1.73m2 or end-stage kidney disease receiving RRT)
- Hemoglobin <8 g/dL (closest value in the prior 3 months)
- Fever (temperature ≥38⁰C) in the last 48h
- Suspected or confirmed bacteremia, endocarditis, or pyelonephritis
- Pneumonia, aspiration, or bilateral pulmonary infiltrates from an infectious etiology reported on chest x-ray or CT scan in the last 7d
- Positive COVID-19 test within previous 10d
- Chronic iron overload (including conditions such as hemochromatosis and beta thalassemia major) or previous iron chelation therapy (including prior participation in DEFEAT-AKI)
- Known hypersensitivity to deferoxamine
- Taking prochlorperazine
- Severe hearing loss
- Pregnant or breastfeeding
- Prisoner
- Concurrent participation in another interventional research study in which the intervention has potential interaction with deferoxamine
- Surgery to be performed under conditions of circulatory arrest
- Receiving extracorporeal membrane oxygenation
- Durable ventricular assist device (VAD) prior to surgery (does not include Impella device or intra-aortic balloon pump)
- Any condition which, in the judgement of the investigator, might increase the risk to the patient
- Conflict with other research studies
Sites / Locations
- Massachusetts General HospitalRecruiting
- Brigham and Women's HospitalRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Deferoxamine
Placebo
Arm Description
Deferoxamine 30mg/kg (max dose, 6g) intravenous infusion (diluted in 240mL normal saline) administered over 12 hours
Normal saline (240mL) intravenous infusion over 12 hours
Outcomes
Primary Outcome Measures
Acute Kidney Injury
Composite outcome that includes any of the following:
Urine output <0.5 ml/kg/h for ≥6 consecutive hours within the first 48h or until the Foley catheter is removed, whichever occurs first
Increase in serum creatinine ≥0.3 mg/dl within the first 48h
Increase in serum creatinine ≥50% within 7 days
Receipt of renal replacement therapy within 7 days
Secondary Outcome Measures
Renal tubular injury
Urine levels of NGAL and KIM-1
Major Adverse Kidney Events
Increase in serum creatinine ≥100%, receipt of renal replacement therapy, or death within 7 days
Postoperative myocardial injury
Peak postoperative troponin I elevation >10 times the 99th percentile upper reference limit
Atrial fibrillation or atrial flutter
New onset postoperative atrial fibrillation or atrial flutter (patients with atrial fibrillation or atrial flutter at baseline will be excluded)
Prolonged mechanical ventilation
Requirement for mechanical ventilation >24h postoperatively
Vasoactive-Inotropic Score
Validated method for integrating all IV vasoactive medications and their doses on an hourly basis into a single measure
Time to liberation from vasoactive medications
Number of hours from time of incision to liberation from all IV vasoactive medications
Sepsis
Life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction is defined as an acute increase in the total SOFA score ≥2 points consequent to the infection.
Ventilator-free days
28 minus the number of days ventilated. Patients who die within 28 days will be assigned 0 ventilator-free days.
ICU-free days
28 minus the number of days in the ICU. Patients who die within 28 days will be assigned 0 ICU-free days.
Hospital-free days
28 minus the number of days hospitalized. Patients who die within 28 days will be assigned 0 hospital-free days.
Full Information
NCT ID
NCT04633889
First Posted
November 12, 2020
Last Updated
June 19, 2023
Sponsor
Brigham and Women's Hospital
Collaborators
Massachusetts General Hospital, Beth Israel Deaconess Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT04633889
Brief Title
Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury
Acronym
DEFEAT-AKI
Official Title
Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 13, 2021 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Massachusetts General Hospital, Beth Israel Deaconess Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multiple lines of evidence support a central role of iron in causing acute kidney injury (AKI), including the finding that prophylactic administration of iron chelators attenuates AKI in animal models. Patients undergoing cardiac surgery may be particularly susceptible to iron-mediated kidney injury due to the profound hemolysis that often occurs from cardiopulmonary bypass. The investigators will test in a phase 2, randomized, double-blind, placebo-controlled trial whether prophylactic administration of deferoxamine decreases the incidence of AKI following cardiac surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Deferoxamine
Arm Type
Experimental
Arm Description
Deferoxamine 30mg/kg (max dose, 6g) intravenous infusion (diluted in 240mL normal saline) administered over 12 hours
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal saline (240mL) intravenous infusion over 12 hours
Intervention Type
Drug
Intervention Name(s)
Deferoxamine
Intervention Description
Deferoxamine 30mg/kg (max dose, 6g) intravenous infusion (diluted in 240mL normal saline) administered over 12 hours
Intervention Type
Drug
Intervention Name(s)
Normal saline
Intervention Description
Normal saline (240mL) intravenous infusion over 12 hours
Primary Outcome Measure Information:
Title
Acute Kidney Injury
Description
Composite outcome that includes any of the following:
Urine output <0.5 ml/kg/h for ≥6 consecutive hours within the first 48h or until the Foley catheter is removed, whichever occurs first
Increase in serum creatinine ≥0.3 mg/dl within the first 48h
Increase in serum creatinine ≥50% within 7 days
Receipt of renal replacement therapy within 7 days
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Renal tubular injury
Description
Urine levels of NGAL and KIM-1
Time Frame
3 days
Title
Major Adverse Kidney Events
Description
Increase in serum creatinine ≥100%, receipt of renal replacement therapy, or death within 7 days
Time Frame
7 days
Title
Postoperative myocardial injury
Description
Peak postoperative troponin I elevation >10 times the 99th percentile upper reference limit
Time Frame
2 days
Title
Atrial fibrillation or atrial flutter
Description
New onset postoperative atrial fibrillation or atrial flutter (patients with atrial fibrillation or atrial flutter at baseline will be excluded)
Time Frame
7 days
Title
Prolonged mechanical ventilation
Description
Requirement for mechanical ventilation >24h postoperatively
Time Frame
24 hours
Title
Vasoactive-Inotropic Score
Description
Validated method for integrating all IV vasoactive medications and their doses on an hourly basis into a single measure
Time Frame
24 hours
Title
Time to liberation from vasoactive medications
Description
Number of hours from time of incision to liberation from all IV vasoactive medications
Time Frame
7 days
Title
Sepsis
Description
Life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction is defined as an acute increase in the total SOFA score ≥2 points consequent to the infection.
Time Frame
7 days
Title
Ventilator-free days
Description
28 minus the number of days ventilated. Patients who die within 28 days will be assigned 0 ventilator-free days.
Time Frame
28 days
Title
ICU-free days
Description
28 minus the number of days in the ICU. Patients who die within 28 days will be assigned 0 ICU-free days.
Time Frame
28 days
Title
Hospital-free days
Description
28 minus the number of days hospitalized. Patients who die within 28 days will be assigned 0 hospital-free days.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Undergoing coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass
AKI risk score ≥6 at the time of screening
Written informed consent from the patient or surrogate
Exclusion Criteria:
AKI, defined as any of the following:
Increase in serum creatinine ≥0.3 mg/dl in 48h
Increase in serum creatinine ≥50% in 7d (if no value available in last 7d, use most recent value in last 3 months)
Urine output ≤0.5 ml/kg/h x 6 consecutive hours (only assessed in patients with hourly monitoring via Foley catheter)
Receipt of renal replacement therapy (RRT) within 7d
Advanced chronic kidney disease (eGFR <15 ml/min/1.73m2 or end-stage kidney disease receiving RRT)
Hemoglobin <8 g/dL (closest value in the prior 3 months)
Fever (temperature ≥38⁰C) in the last 48h
Suspected or confirmed bacteremia, endocarditis, or pyelonephritis
Pneumonia, aspiration, or bilateral pulmonary infiltrates from an infectious etiology reported on chest x-ray or CT scan in the last 7d
Positive COVID-19 test within previous 10d
Chronic iron overload (including conditions such as hemochromatosis and beta thalassemia major) or previous iron chelation therapy (including prior participation in DEFEAT-AKI)
Known hypersensitivity to deferoxamine
Taking prochlorperazine
Severe hearing loss
Pregnant or breastfeeding
Prisoner
Concurrent participation in another interventional research study in which the intervention has potential interaction with deferoxamine
Surgery to be performed under conditions of circulatory arrest
Receiving extracorporeal membrane oxygenation
Durable ventricular assist device (VAD) prior to surgery (does not include Impella device or intra-aortic balloon pump)
Any condition which, in the judgement of the investigator, might increase the risk to the patient
Conflict with other research studies
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David E. Leaf, MD, MMSc
Phone
9144190622
Email
deleaf@bwh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Shahzad Shaefi, MD, MPH
Phone
6178203570
Email
sshaefi@bidmc.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David E. Leaf, MD, MMSc
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aranya Bagchi, MBBS
Email
abagchi@mgh.harvard.edu
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David E. Leaf, MD, MMSc
Phone
914-419-0622
Email
deleaf@bwh.harvard.edu
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shahzad Shaefi, MD, MPH
Email
sshaefi@bidmc.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31554656
Citation
Sharma S, Leaf DE. Iron Chelation as a Potential Therapeutic Strategy for AKI Prevention. J Am Soc Nephrol. 2019 Nov;30(11):2060-2071. doi: 10.1681/ASN.2019060595. Epub 2019 Sep 25.
Results Reference
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Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury
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