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

Acute Kidney Injury Clinical Trial

— DEFEAT-AKI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04633889
• Other study ID #: 2020P003605
• Secondary ID: R01DK125786
• Status: Recruiting
• Phase: Phase 2
• Start date: April 13, 2021
• Est. completion date: October 1, 2024

Study information

• Verified date: May 2024
• Source: Brigham and Women's Hospital
• Contact: David E. Leaf, MD, MMSc
• Phone: 9144190622
• Email: deleaf[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: October 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 =38°C) 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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

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

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Beth Israel Deaconess Medical Center, Massachusetts General Hospital, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	7 days
Secondary	Renal tubular injury	Urine levels of NGAL and KIM-1	3 days
Secondary	Major Adverse Kidney Events	Increase in serum creatinine =100%, receipt of renal replacement therapy, or death within 7 days	7 days
Secondary	Postoperative myocardial injury	Peak postoperative troponin I elevation >10 times the 99th percentile upper reference limit	2 days
Secondary	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)	7 days
Secondary	Prolonged mechanical ventilation	Requirement for mechanical ventilation >24h postoperatively	24 hours
Secondary	Vasoactive-Inotropic Score	Validated method for integrating all IV vasoactive medications and their doses on an hourly basis into a single measure	24 hours
Secondary	Time to liberation from vasoactive medications	Number of hours from time of incision to liberation from all IV vasoactive medications	7 days
Secondary	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.	7 days
Secondary	Ventilator-free days	28 minus the number of days ventilated. Patients who die within 28 days will be assigned 0 ventilator-free days.	28 days
Secondary	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.	28 days
Secondary	Hospital-free days	28 minus the number of days hospitalized. Patients who die within 28 days will be assigned 0 hospital-free days.	28 days