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

Mass General Brigham

Status and phase: Active, not recruiting; Phase 2

Conditions: Acute Kidney Injury

Treatments: Drug: Deferoxamine; Drug: Normal saline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04633889

R01DK125786 (U.S. NIH Grant/Contract)

2020P003605

Details and patient eligibility

About

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.

Enrollment: 320 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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320 participants in 2 patient groups, including a placebo group

Deferoxamine

Experimental group

Description:

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

Treatment:

Drug: Deferoxamine

Placebo

Placebo Comparator group

Description:

Normal saline (240mL) intravenous infusion over 12 hours

Treatment:

Drug: Normal saline