Deferoxamine for Cardiac Surgery-Associated Acute Kidney Injury

(DEFEAT-AKI Trial)

Recruiting at 2 trial locations

Overseen By David E. Leaf, MD, MMSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Prochlorperazine

Disqualifiers: AKI, Advanced chronic kidney disease, Fever, Chronic iron overload, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

320 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking prochlorperazine. It's best to discuss your medications with the trial team.

What data supports the effectiveness of the drug Deferoxamine for preventing kidney damage during cardiac surgery?

Research shows that Deferoxamine can protect kidneys from damage caused by toxic substances and improve kidney function after cold storage in transplants. It works by reducing harmful oxidative stress and improving blood flow, which suggests it might help prevent kidney injury during cardiac surgery. ^{1 2 3 4 5}

How does the drug Deferoxamine differ from other treatments for cardiac surgery-associated acute kidney injury?

Deferoxamine is unique because it acts as a chelating agent, which means it binds to and removes excess iron and other metals from the body, potentially reducing oxidative stress and protecting the kidneys. This mechanism is different from other treatments that may not target metal-induced oxidative damage. ^{1 2 4 6 7}

What is the purpose of this trial?

This trial is testing whether a medication called deferoxamine can prevent kidney damage in patients having heart surgery. These patients are at risk because surgery can release a lot of iron into their blood, which can harm their kidneys. Deferoxamine helps by removing this excess iron. Deferoxamine has been used to treat conditions where there is too much iron in the body.

Research Team

David E. Leaf, MD, MMSc

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults over 18 who are at risk of acute kidney injury (AKI) and are undergoing heart surgery with cardiopulmonary bypass. They must have an AKI risk score of ≥6, not be pregnant or breastfeeding, and cannot be in another study that could interfere with this one. People with severe chronic kidney disease, recent infections, fever, or certain conditions like iron overload can't join.

Inclusion Criteria

I am scheduled for heart surgery that involves bypass or valve replacement.

Written informed consent from the patient or surrogate

Your risk for acute kidney injury is high, with a score of 6 or more at the time of screening.

Exclusion Criteria

Your urine output is less than half a milliliter per kilogram of body weight per hour for six hours in a row, and you are being monitored every hour with a Foley catheter.

Your kidney function has significantly worsened in the past week, or if there's no recent test, then the most recent test in the last 3 months shows a significant change.

I have had a fever of 38°C or higher in the last 48 hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either deferoxamine or placebo intravenously over 12 hours during cardiac surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute kidney injury and other secondary outcomes

28 days

Treatment Details

Interventions

• Deferoxamine

Trial Overview The trial is testing if Deferoxamine, a drug that removes excess iron from the body (iron chelator), can prevent AKI after heart surgery compared to a placebo (normal saline). It's a phase 2 study where patients are randomly assigned to receive either Deferoxamine or placebo in a double-blind manner—neither they nor the doctors know which one they're getting.

Participant Groups

Group I: Deferoxamine Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Normal saline (240mL) intravenous infusion over 12 hours

Deferoxamine is already approved in United States, European Union for the following indications:

Approved in United States as Desferal for:

• Acute Iron Poisoning
• Chronic Iron Overload

Approved in European Union as Desferal for:

• Iron overload
• Aluminum toxicity

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

In a study of 84 pediatric patients treated with deferoxamine (DFO) for transfusional hemochromatosis, only 1.2% experienced ocular toxicity, indicating that such side effects are rare when regular ophthalmic screenings are conducted.

The single case of ocular toxicity was mild and reversible, suggesting that with proper monitoring and dose adjustments, the risks associated with DFO treatment can be effectively managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferoxamine-related ocular toxicity: incidence and outcome in a pediatric population. Baath, JS., Lam, WC., Kirby, M., et al.[2013]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: role of Cr(VI) chelation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Deferoxamine-related ocular toxicity: incidence and outcome in a pediatric population. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Deferoxamine reduces cold-ischemic renal injury in a syngeneic kidney transplant model. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

[Experimental research on the use of deferoxamine in the prevention of renal damage from acute ischemia]. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Precipitation of dialysis dementia by deferoxamine treatment of aluminum-related bone disease. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs. [2022]