Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury

Phase 2

Completed

• Conditions: Acute Kidney Injury
• Interventions: Drug: Deferoxamine; Drug: Normal saline

• Registration Number: NCT04633889
• Lead Sponsor: Brigham and Women's Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-11-12
• Study First Submitted QC: 2020-11-12
• Study First Posted: 2020-11-18
• Study Start: 2021-04-13
• Primary Completion: 2024-08-26
• Study Completion: 2024-12-14
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 320

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Deferoxamine	Deferoxamine	Deferoxamine 30mg/kg (max dose, 6g) intravenous infusion (diluted in 240mL normal saline) administered over 12 hours
Placebo	Normal saline	Normal saline (240mL) intravenous infusion over 12 hours

Primary Outcome Measures

Name	Time	Method
Acute Kidney Injury	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

Name	Time	Method
Time to liberation from vasoactive medications	7 days	Number of hours from time of incision to liberation from all IV vasoactive medications
Renal tubular injury	3 days	Urine levels of NGAL and KIM-1
Major Adverse Kidney Events	7 days	Increase in serum creatinine ≥100%, receipt of renal replacement therapy, or death within 7 days
Prolonged mechanical ventilation	24 hours	Requirement for mechanical ventilation \>24h postoperatively
Sepsis	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.
Ventilator-free days	28 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 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 days	28 minus the number of days hospitalized. Patients who die within 28 days will be assigned 0 hospital-free days.
Postoperative myocardial injury	2 days	Peak postoperative troponin I elevation \>10 times the 99th percentile upper reference limit
Atrial fibrillation or atrial flutter	7 days	New onset postoperative atrial fibrillation or atrial flutter (patients with atrial fibrillation or atrial flutter at baseline will be excluded)
Vasoactive-Inotropic Score	24 hours	Validated method for integrating all IV vasoactive medications and their doses on an hourly basis into a single measure

Trial Locations

Locations (3)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States