Clinical trial NCT04633889: Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury
Official title: Deferoxamine for the Prevention of Cardiac Surgery-Associated Acute Kidney Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: Beth Israel Deaconess Medical Center
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-11-18
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Acute Kidney Injury
timeFrame: 7 days
Secondary outcomes:
measure: Renal tubular injury
timeFrame: 3 days
measure: Major Adverse Kidney Events
timeFrame: 7 days
measure: Postoperative myocardial injury
timeFrame: 2 days
measure: Atrial fibrillation or atrial flutter
timeFrame: 7 days
measure: Prolonged mechanical ventilation
timeFrame: 24 hours
measure: Vasoactive-Inotropic Score
timeFrame: 24 hours
measure: Time to liberation from vasoactive medications
timeFrame: 7 days
measure: Sepsis
timeFrame: 7 days
measure: Ventilator-free days
timeFrame: 28 days
measure: ICU-free days
timeFrame: 28 days
measure: Hospital-free days
timeFrame: 28 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: David E. Leaf, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References:
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.