Deferiprone Therapy for Heart Attack

(MIRON-DFP Trial)

Overseen By Clinical Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rohan Dharmakumar

Must not be taking: Iron chelators

Disqualifiers: Prior MI, LVEF < 40%, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Deferiprone, a medication, can reduce iron buildup in the heart after a heart attack. Researchers aim to determine if this treatment benefits those who have experienced a hemorrhagic myocardial infarction, a heart attack with bleeding in the heart muscle. Participants will receive either Deferiprone or a placebo, a substance with no active drug, to compare results. Individuals who recently had an anterior wall STEMI and underwent emergency heart surgery may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using investigational drugs or devices, you must stop them 30 days before joining the trial.

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

Research shows that Deferiprone, a drug that helps remove excess iron from the body, has been studied for safety in people with certain heart conditions. In earlier studies, Deferiprone managed excess iron in patients with thalassemia, a blood disorder. These studies found that while Deferiprone effectively lowers iron levels, it can also cause side effects. Reported side effects include joint pain, nausea, and a decrease in white blood cells, which can weaken the body's ability to fight infections.

Deferiprone is already approved by the FDA for treating iron overload in other conditions, providing existing safety information. However, this information might not fully apply to its use for heart attack recovery. Ongoing research aims to confirm its safety for this specific purpose. Participants in the current trial should be aware of the potential for side effects and discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart attack?

Unlike standard treatments for heart attacks, which typically focus on reducing blood clot formation or improving blood flow, Deferiprone takes a unique approach by targeting iron overload in heart tissue. Researchers are excited about this treatment because Deferiprone is an iron chelator, meaning it helps to remove excess iron from the body, potentially reducing damage to heart tissue after a myocardial infarction. This is particularly important in cases of hemorrhagic myocardial infarction, where iron from blood can exacerbate heart damage. By addressing iron overload, Deferiprone could offer a novel way to protect the heart and improve recovery outcomes.

What evidence suggests that Deferiprone might be an effective treatment for myocardial infarction?

Research has shown that Deferiprone helps remove excess iron from the body, which is crucial because too much iron can damage the heart, especially after a heart attack. In this trial, some participants will receive Deferiprone to evaluate its effectiveness in various types of myocardial infarction. Studies suggest that Deferiprone may remove iron from the heart more effectively than other treatments. By reducing iron levels, it may help protect the heart from further damage. Although more research is needed specifically for heart attacks, Deferiprone has shown promise in treating heart problems in other conditions. ^{2 3 5 6 7}

Who Is on the Research Team?

Rohan Dharmakumar, PhD

Principal Investigator

Krannert Cardiovascular Research Center

Keyur Vora, MD MS

Principal Investigator

Krannert Cardiovascular Research Center

Are You a Good Fit for This Trial?

This trial is for adults who've recently had a specific type of heart attack (anterior wall STEMI) and are about to have a procedure to open their blocked arteries. They must not have had previous heart attacks or procedures, severe kidney issues, known allergies to MRI contrast agents, or be pregnant. Their body weight should be under 309 lbs., and they can't have certain blood disorders or liver problems.

Inclusion Criteria

I had a specific type of heart attack affecting the front wall of my heart, confirmed by symptoms, ECG changes, and high heart markers.

Exclusion Criteria

Any clinically significant abnormality identified prior to randomization that in the judgment of the Sponsor-Investigator or Delegate would preclude safe completion of the study or confound the anticipated benefit of LIPOMED

My body weight is over 309 lbs.

Absolute neutrophil count of ANC < 1.0 x 109 /L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Deferiprone or placebo to assess its efficacy in reducing free iron in the hemorrhagic zone of myocardial infarction

6 months

Follow-up

Participants are monitored for safety, tolerability, and treatment effects, including clinical outcomes and side effects

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Deferiprone
• Placebo

Trial Overview The study tests if Deferiprone tablets can reduce iron in the damaged area of the heart after a hemorrhagic myocardial infarction. Patients will either receive Deferiprone or a placebo randomly, alongside standard care including an MRI scan to guide treatment.

How Is the Trial Designed?

Group I: Hemorrhagic Myocardial Infarction - Deferiprone Active Control 1 Intervention

Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage

Group II: Non-hemorrhagic Myocardial Infarction - Deferiprone Active Control 1 Intervention

Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage

Group III: Hemorrhagic Myocardial Infarction - Placebo Placebo Group 1 Intervention

Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage

Group IV: Non-hemorrhagic Myocardial Infarction - Placebo Placebo Group 1 Intervention

Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage

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

Approved in European Union as Ferriprox for:

• Iron overload in thalassaemia major

Approved in United States as Ferriprox for:

• Transfusional iron overload in patients with thalassemia syndromes

Approved in Canada as Ferriprox for:

• Iron overload in thalassemia syndromes

Who Is Running the Clinical Trial?

Rohan Dharmakumar

Lead Sponsor

Trials

10

Recruited

120,000+

Cardio-theranostics LLC

Collaborator

Trials

1

Recruited

70+

Lipomed AG

Collaborator

Trials

1

Recruited

70+

Published Research Related to This Trial

Deferiprone is an effective oral iron chelator that can match or exceed the efficacy of deferoxamine in removing excess iron, particularly improving myocardial siderosis in patients with thalassemia major.

While deferiprone can cause serious side effects like agranulocytosis in about 1% of patients, it is generally well-tolerated and can be combined with deferoxamine for better management of severe iron overload, especially in patients who struggle with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferiprone in the treatment of transfusion-dependent thalassemia: a review and perspective. Galanello, R.[2023]

Deferiprone is an effective oral iron-chelating agent that reduces cardiac iron load and improves cardiac function in patients with transfusion-related hemosiderosis, significantly enhancing their prognosis.

While generally well tolerated, deferiprone can cause serious side effects such as agranulocytosis (0.5%) and neutropenia (9%), necessitating regular blood count monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of iron chelation therapy with deferiprone in patients with transfusion-dependent thalassemia. Jamuar, SS., Lai, AH.[2021]

Captopril significantly reduced the occurrence of ventricular fibrillation during reperfusion in isolated rat hearts, with none of the captopril-treated hearts experiencing this arrhythmia, compared to 4 out of 6 enalapril-treated hearts.

Captopril and HOE 498 improved mechanical function after reperfusion, maintaining a pressure-rate index of 124% and 98% of initial values, respectively, while untreated and enalapril-treated hearts showed severe impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498. van Gilst, WH., de Graeff, PA., Wesseling, H., et al.[2016]

Captopril, an angiotensin converting enzyme inhibitor, can trigger myocardial ischemic events in patients with coronary artery disease, especially after stopping beta-blockers like propranolol.

In two case studies, one patient experienced multiple angina episodes and another showed signs of a possible acute myocardial infarction after the combination of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ischemic cardiovascular complications concurrent with administration of captopril. A clinical note. Baker, KM., Johns, DW., Ayers, CR., et al.[2019]

Deferiprone appears to be more effective than deferoxamine in protecting the heart from iron overload, as indicated by better myocardial imaging results and a lower risk of developing or worsening cardiac disease in patients on long-term treatment.

Combining deferiprone with deferoxamine may enhance iron excretion and reduce the time needed to treat severe iron overload and reverse heart disease, although these findings need further validation through randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferiprone: New insight. Piga, A., Roggero, S., Vinciguerra, T., et al.[2018]

Defibrotide, when administered in doses of 100-800 mg, significantly reduces plasminogen activator inhibitor (PAI) levels and increases tissue plasminogen activator (t-PA) and prostacyclin levels in human venous blood, indicating its potential efficacy in promoting fibrinolysis.

The study also found that defibrotide inhibits neutrophil activation in vitro by reducing calcium entry into cells, suggesting a mechanism of action that may involve interference with adenosine receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of venous endothelial activity and transcellular calcium transport by defibrotide: the adenosine hypothesis. Pasini, FL., Frigerio, C., Capecchi, PL., et al.[2014]

Defibrase (DF), a fibrinolytic agent, was effective in recanalizing blocked coronary arteries in patients with acute myocardial infarction, achieving a 100% success rate in the DF group compared to only 27% in the control group.

While DF showed a trend towards improved left ventricular function (LVEF of 61% vs 50% in controls), it also caused minor bleeding complications, such as petechiae and gum bleeding, but no serious adverse effects like intracranial hemorrhage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Coronary thrombolysis with defibrase]. Li, TD., Gai, LY., Wang, SR.[2014]

In a study of 157 patients with acute myocardial infarction (AMI), defibrase demonstrated effective thrombolytic properties, achieving a recanalization rate of 57% in patients with total occlusion of the infarct-related artery (IRA) shortly after treatment.

Defibrase treatment resulted in a lower mortality and complication rate compared to conventional therapy, with a low incidence of major bleeding complications, indicating it is a safe and effective option for thrombolysis in AMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defibrase, a purified fibrinolytic protease from snake venom in acute myocardial infarction. Huang, DX., Gai, LY., Wang, SR., et al.[2017]

Deferiprone, an oral iron chelator, was found to enhance the anticancer effects of daunorubicin in leukemia cells without reducing its effectiveness, suggesting it could be a useful adjunct in cancer treatment.

However, in an in vivo rabbit model, deferiprone did not provide significant protection against the cardiotoxic effects of daunorubicin, indicating that its role in preventing heart damage from anthracyclines may be more complex than previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferiprone does not protect against chronic anthracycline cardiotoxicity in vivo. Popelová, O., Sterba, M., Simůnek, T., et al.[2018]

In a study of thalassemia major patients, those treated with deferiprone showed no cardiac events during therapy or for at least 18 months after, while 52 cardiac events occurred in patients treated only with deferoxamine (DFO).

Deferiprone therapy was associated with significantly greater cardiac protection compared to DFO, suggesting it may be a safer option for preventing cardiac disease in thalassemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Borgna-Pignatti, C., Cappellini, MD., De Stefano, P., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4490296/

Effects of deferasirox-deferoxamine on myocardial and liver ... Both high-dose DFO monotherapy and deferiprone-DFO combination therapy may have a role in treating thalassemia-major patients with heart failure (LVEF <56%); ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05604131?term=Dharmakumar%20&rank=2

NCT05604131 | Cardiac MRI-guided Deferiprone Therapy ... ... disease (that is, the drug's effectiveness). For example, participants ... Treatment Effect: Clinical Outcomes of Acute Heart Failure, The proportion of ...

3. canjhealthtechnol.ca canjhealthtechnol.ca/index.php/cjht/article/view/SR0741r/1349

View of Deferiprone (Ferriprox) ... heart failure, renal tubular injury, and endocrinopathies.- If left untreated, iron overload can lead to organ failure and/or death. Repeated ...

4. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.106.648790

A Randomized, Placebo-Controlled, Double-Blind Trial of ... Left ventricular (LV) dysfunction and heart failure occur late in the disease process, can be resistant to treatment, and carry a poor prognosis ...

5. haematologica.org haematologica.org/article/view/2727

Comparative effects of deferiprone and deferoxamine on ... Deferiprone is an iron chelator that has the potential to be more effective than deferoxamine in removing intracellular iron from the heart. ... cardiac disease ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2983007/

Efficacy and safety of deferiprone (Ferriprox), an oral iron- ... Cardiac evaluation was limited to patients with a history of the symptoms of heart failure and/or arrhythmia. ... cardiac disease in patients with thalassemia ...

7. ema.europa.eu ema.europa.eu/en/documents/variation-report/ferriprox-h-c-236-ii-0103-epar-assessment-report-variation_en.pdf

Ferriprox, INN-deferiprone - EMA As safety data of the combination deferiprone ... Main causes of mortality are sudden cardiac death, arrhythmia, and heart failure from cardiac ...