Deferoxamine for Cardiac Surgery-Associated Acute Kidney Injury

(DEFEAT-AKI Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether deferoxamine, an iron-chelating agent, can prevent acute kidney injury (AKI) in individuals undergoing heart surgery. Researchers believe iron plays a key role in causing AKI, particularly in heart surgery patients, as the procedure can increase iron levels in the body. Participants will receive either deferoxamine or a placebo to determine if deferoxamine reduces the risk of AKI. Ideal candidates for this trial are those undergoing heart surgery with a heart-lung machine and at risk for kidney issues post-surgery. As a Phase 2 trial, this research focuses on assessing deferoxamine's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that deferoxamine is likely to be safe for humans?

Research has shown that deferoxamine, a treatment under study to prevent kidney damage after heart surgery, is generally well-tolerated. It has been used safely for managing iron overload from frequent blood transfusions, demonstrating a history of safety in those situations.

The FDA has approved deferoxamine for treating iron overload, indicating a good safety record for that purpose. Although using deferoxamine specifically to prevent kidney damage in heart surgery patients remains under study, its existing safety record offers some reassurance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cardiac surgery-associated acute kidney injury focus on managing symptoms and supporting kidney function. But Deferoxamine works differently, targeting the underlying issue of iron overload, which can damage kidney tissues during surgery. Researchers are excited about Deferoxamine because it acts as an iron chelator, removing excess iron and potentially reducing kidney damage. This unique mechanism could offer a protective benefit beyond what's currently available, making it a promising option for better outcomes in patients.

What evidence suggests that deferoxamine might be an effective treatment for acute kidney injury?

Research has shown that deferoxamine, which participants in this trial may receive, can protect kidneys from damage caused by harmful substances. In kidney transplants, deferoxamine improved kidney function after cold storage. Studies suggest that excess iron in the body significantly contributes to sudden kidney problems, especially during heart surgery. Deferoxamine helps by removing extra iron, potentially lowering the risk of these kidney issues. Early studies demonstrated that using deferoxamine to bind and remove iron may prevent sudden kidney problems and other organ injuries. ^{1 2 3 6 7}

Who Is on the Research Team?

David E. Leaf, MD, MMSc

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04633889?cond=%22Acute%20Kidney%20Failure%22&intr=%22chelating%20agents%22&viewType=Table&rank=1

Deferoxamine for the Prevention of Cardiac Surgery ...

Most clinical studies have one primary outcome measure, but some have more than one. ... The main reason for the clinical trial. The types of primary purpose are: ...

2.

withpower.com

withpower.com/trial/phase-3-acute-kidney-injury-3-2021-76b0f

Deferoxamine for Cardiac Surgery-Associated Acute Kidney Injury

Research shows that Deferoxamine can protect kidneys from damage caused by toxic substances and improve kidney function after cold storage in transplants. It ...

3.

reporter.nih.gov

reporter.nih.gov/search/0bYYWmFFiE6IqTiXD_6slA/project-details/10249293

Deferoxamine for the Prevention of Acute Kidney Injury

Abundant data suggest that iron excess plays a key role in AKI, particularly in the setting of cardiac surgery. We propose a 3-center, double-blind, randomized ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6830795/

Iron Chelation as a Potential Therapeutic Strategy for AKI ...

Small studies have investigated iron chelation as a novel therapeutic strategy for prevention of AKI and extrarenal acute organ injury, and have demonstrated ...

5.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT04633889/deferoxamine-for-the-prevention-of-cardiac-surgery-associated-acute-kidney-injury

Deferoxamine for the Prevention of Cardiac Surgery ...

Study Summary. Multiple lines of evidence support a central role of iron in causing acute kidney injury (AKI), including the finding that ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2007/016267s044lbl.pdf

Desferal (deferoxamine mesylate) for injection

Desferal is indicated for the treatment of acute iron intoxication and of chronic iron overload due to transfusion-dependent anemias. Acute Iron Intoxication.

7.

novartis.com

novartis.com/us-en/sites/novartis_us/files/desferal.pdf

Desferal

HIGHLIGHTS OF PRESCRIBING INFORMATION. These highlights do not include all the information needed to use DESFERAL safely and effectively.