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Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury (DEFEAT-AKI)

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ClinicalTrials.gov Identifier: NCT04633889
Recruitment Status : Recruiting
First Posted : November 18, 2020
Last Update Posted : November 23, 2022
Sponsor:
Collaborators:
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
David Leaf, Brigham and Women's Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Drug: Deferoxamine Drug: Normal saline Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury
Actual Study Start Date : April 13, 2021
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : August 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arms and Interventions
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Arm Intervention/treatment
Experimental: Deferoxamine
Deferoxamine 30mg/kg (max dose, 6g) intravenous infusion (diluted in 240mL normal saline) administered over 12 hours
 Drug: Deferoxamine
Deferoxamine 30mg/kg (max dose, 6g) intravenous infusion (diluted in 240mL normal saline) administered over 12 hours
Placebo Comparator: Placebo
Normal saline (240mL) intravenous infusion over 12 hours
 Drug: Normal saline
Normal saline (240mL) intravenous infusion over 12 hours


Outcome Measures
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Primary Outcome Measures :
  1. Acute Kidney Injury [ Time Frame: 7 days ]

    Composite outcome that includes any of the following:

    1. 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
    2. Increase in serum creatinine ≥0.3 mg/dl within the first 48h
    3. Increase in serum creatinine ≥50% within 7 days
    4. Receipt of renal replacement therapy within 7 days


Secondary Outcome Measures :
  1. Renal tubular injury [ Time Frame: 3 days ]
    Urine levels of NGAL and KIM-1

  2. Major Adverse Kidney Events [ Time Frame: 7 days ]
    Increase in serum creatinine ≥100%, receipt of renal replacement therapy, or death within 7 days

  3. Postoperative myocardial injury [ Time Frame: 2 days ]
    Peak postoperative troponin I elevation >10 times the 99th percentile upper reference limit

  4. Atrial fibrillation or atrial flutter [ Time Frame: 7 days ]
    New onset postoperative atrial fibrillation or atrial flutter (patients with atrial fibrillation or atrial flutter at baseline will be excluded)

  5. Prolonged mechanical ventilation [ Time Frame: 24 hours ]
    Requirement for mechanical ventilation >24h postoperatively

  6. Vasoactive-Inotropic Score [ Time Frame: 24 hours ]
    Validated method for integrating all IV vasoactive medications and their doses on an hourly basis into a single measure

  7. Time to liberation from vasoactive medications [ Time Frame: 7 days ]
    Number of hours from time of incision to liberation from all IV vasoactive medications

  8. Sepsis [ Time Frame: 7 days ]
    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.

  9. Ventilator-free days [ Time Frame: 28 days ]
    28 minus the number of days ventilated. Patients who die within 28 days will be assigned 0 ventilator-free days.

  10. ICU-free days [ Time Frame: 28 days ]
    28 minus the number of days in the ICU. Patients who die within 28 days will be assigned 0 ICU-free days.

  11. Hospital-free days [ Time Frame: 28 days ]
    28 minus the number of days hospitalized. Patients who die within 28 days will be assigned 0 hospital-free days.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years
  2. Undergoing coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass
  3. AKI risk score ≥6 at the time of screening
  4. Written informed consent from the patient or surrogate

Exclusion Criteria:

  1. 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
  2. Advanced chronic kidney disease (eGFR <15 ml/min/1.73m2 or end-stage kidney disease receiving RRT)
  3. Hemoglobin <8 g/dL (closest value in the prior 3 months)
  4. Fever (temperature ≥38⁰C) in the last 48h
  5. Suspected or confirmed bacteremia, endocarditis, or pyelonephritis
  6. Pneumonia, aspiration, or bilateral pulmonary infiltrates from an infectious etiology reported on chest x-ray or CT scan in the last 7d
  7. Positive COVID-19 test within previous 10d
  8. Chronic iron overload (including conditions such as hemochromatosis and beta thalassemia major) or previous iron chelation therapy (including prior participation in DEFEAT-AKI)
  9. Known hypersensitivity to deferoxamine
  10. Taking prochlorperazine
  11. Severe hearing loss
  12. Pregnant or breastfeeding
  13. Prisoner
  14. Concurrent participation in another interventional research study in which the intervention has potential interaction with deferoxamine
  15. Surgery to be performed under conditions of circulatory arrest
  16. Receiving extracorporeal membrane oxygenation
  17. Durable ventricular assist device (VAD) prior to surgery (does not include Impella device or intra-aortic balloon pump)
  18. Any condition which, in the judgement of the investigator, might increase the risk to the patient
  19. Conflict with other research studies
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04633889


Contacts
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Contact: David E. Leaf, MD, MMSc 9144190622 deleaf@bwh.harvard.edu
Contact: Shahzad Shaefi, MD, MPH 6178203570 sshaefi@bidmc.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Aranya Bagchi, MBBS       abagchi@mgh.harvard.edu   
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: David E. Leaf, MD, MMSc    914-419-0622    deleaf@bwh.harvard.edu   
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Shahzad Shaefi, MD, MPH       sshaefi@bidmc.harvard.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: David E. Leaf, MD, MMSc Brigham and Women's Hospital
More Information
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Publications:

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Responsible Party: David Leaf, Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04633889    
Other Study ID Numbers: 2020P003605
R01DK125786 ( U.S. NIH Grant/Contract )
First Posted: November 18, 2020    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Acute Kidney Injury
Wounds and Injuries
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Deferoxamine
 Siderophores
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action