Deferiprone for Subarachnoid Hemorrhage

Recruiting at 1 trial location

Overseen By Beth Perry, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: David Hasan

Must not be taking: Antiplatelets, Corticosteroids, Antiepileptics, others

Disqualifiers: Sepsis, Cardiac stunning, Epilepsy, others

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

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug Deferiprone to determine if it can aid individuals who have experienced a subarachnoid hemorrhage (a type of brain bleed) from a burst aneurysm. Researchers aim to discover if Deferiprone can reduce harmful iron buildup in the brain and enhance cognitive function. Participants will receive either Deferiprone or a placebo (a sugar pill) alongside standard treatment. The trial seeks individuals who have suffered a brain bleed from a ruptured aneurysm and have undergone a procedure to secure the aneurysm within 48 hours of the event. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppression therapy, chronic corticosteroids, or antiplatelet treatment, you may not be eligible to participate.

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

Research has shown that deferiprone has been tested in various situations and appears safe to use. In a small study involving individuals with superficial siderosis, a condition involving brain bleeding, deferiprone was found to be safe. The study also demonstrated its effectiveness in reducing iron build-up in the brain, which is promising for treating conditions like subarachnoid hemorrhage (SAH).

Although specific safety data for deferiprone in treating SAH is not available, its approval for other conditions suggests it is generally safe. This indicates it usually does not cause serious side effects for individuals using it for approved purposes.

Thus far, deferiprone appears well-tolerated and could be a useful option for reducing iron build-up in the brain after an SAH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for subarachnoid hemorrhage, which often focus on managing symptoms and preventing complications, deferiprone introduces a novel approach by acting as an iron chelator. This means it helps remove excess iron from the brain, which is thought to contribute to further brain injury after a hemorrhage. Researchers are excited because deferiprone targets the underlying issue of iron accumulation, potentially reducing brain damage more effectively and improving recovery outcomes compared to existing options.

What evidence suggests that Deferiprone might be an effective treatment for subarachnoid hemorrhage?

Research has shown that deferiprone, a drug that helps remove excess iron from the body, might be useful for conditions with excessive iron in the brain. In animal studies, deferiprone prevented blood vessels from narrowing after a brain bleed, reducing this narrowing by 24%. Other studies suggest that deferiprone might improve cognitive function and reduce brain damage after strokes by lowering iron levels in the brain. These findings are promising for conditions like subarachnoid hemorrhage, where excess iron can damage brain cells and impair cognitive abilities. In this trial, participants will receive either deferiprone or a placebo. While more research is needed, these early results offer hope that deferiprone could reduce brain damage and improve recovery for patients with this condition. ^{1 2 6 7 8}

Who Is on the Research Team?

David Hasan, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with recent subarachnoid hemorrhage (SAH) due to a ruptured cerebral aneurysm, who've had successful aneurysm treatment and are stable. Excluded are those with certain types of SAH, previous major health events or surgeries, severe infections, significant other brain issues, uncontrolled hypertension, known allergies to the study drug Deferiprone, or contraindications for MRI.

Inclusion Criteria

My brain hemorrhage is mostly in the upper part of my brain, caused by a specific type of aneurysm.

I was fully independent before my brain hemorrhage.

My aneurysm treatment started within 48 hours of my first symptoms and less than 12 hours after hospital admission.

Exclusion Criteria

Angio-negative SAH

I am on long-term immunosuppression therapy or taking chronic corticosteroids.

I had a brain aneurysm burst in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral deferiprone or placebo for 14 days to assess its effect on ferritin levels in cerebrospinal fluid

2 weeks

Daily visits for CSF sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of functional outcomes and changes in brain structure

12 months

Assessments at 6 weeks, 6 months, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Deferiprone
• Montreal Cognitive Assessment

Trial Overview

The trial tests if Deferiprone pills can reduce iron in the brain and improve thinking skills after SAH. Participants will either receive Deferiprone plus standard care or a placebo plus standard care. The effects will be measured by checking ferritin levels in spinal fluid and cognitive function using the Montreal Cognitive Assessment.

How Is the Trial Designed?

Group I: Deferiprone Experimental Treatment 2 Interventions

This is the drug arm (deferiprone). Patients will receive oral deferiprone

Group II: Control Placebo Group 2 Interventions

this group will only receive the placebo (sugar pill)

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?

David Hasan

Lead Sponsor

Trials

4

Recruited

110+

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

The guidelines for managing subarachnoid hemorrhage were developed based on extensive literature reviews, large international clinical trials, and expert consensus, aiming to improve decision-making for physicians in Croatia.

These guidelines provide evidence-based information on the epidemiology, risk factors, prognosis, and management strategies for subarachnoid hemorrhage, highlighting the importance of timely and appropriate treatment to reduce mortality and complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General recommendations for the management of aneurysmal subarachnoid hemorrhage. Solter, VV., Breitenfeld, T., Roje-Bedeković, M., et al.[2014]

A total of 197 adverse events (AEs) were reported among patients using various intravenous iron products, with ferumoxytol showing the highest rate of AEs at 746 per million units sold, compared to iron sucrose at 5.25 per million.

Ferumoxytol was associated with significantly higher risks of death and serious nonfatal AEs compared to iron sucrose and sodium ferric gluconate, indicating a need for caution when using this newer iron product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rates of reported adverse events associated with i.v. iron products in the United States. Bailie, GR.[2022]

Only 2 out of 15 participants reported adverse drug reactions (ADRs) directly to the MedEffect system, with most opting to inform their physicians or pharmacists instead, highlighting a lack of awareness about the reporting system.

Barriers to reporting included physicians downplaying side effects, confusion about what to report, and a lack of feedback after submission, suggesting that simplifying the MedEffect reporting forms could improve patient engagement in ADR reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' experiences on adverse drug reactions reporting: a qualitative study. Al Dweik, R., Yaya, S., Stacey, D., et al.[2021]

Oral nimodipine is the only FDA-approved medication specifically for preventing and treating neurological deficits after aneurysmal subarachnoid hemorrhage, highlighting its importance in improving patient outcomes.

Fasudil, a Rho-kinase inhibitor, has shown promise in enhancing clinical outcomes for patients with aneurysmal subarachnoid hemorrhage and is approved in some countries, indicating potential for broader therapeutic strategies in managing delayed cerebral ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage. Maruhashi, T., Higashi, Y.[2021]

In a study involving 209 patients with subarachnoid hemorrhage, nimodipine, a calcium channel blocker, was used to address vasospasms, showing promising therapeutic efficacy.

The results indicate that combining nimodipine with hypervolemia and hypertensive agents may be necessary for effective treatment of vasospasm following subarachnoid hemorrhage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience with nimodipine treatment of vascular spasm after subarachnoid hemorrhage]. Wroński, J., Berny, W., Abraszko, R., et al.[2013]

Anticoagulants and antiplatelet drugs are the most frequently reported causes of adverse drug reactions (ADRs) in Germany, with heparins, ticlopidine, phenprocoumon, acetylsalicylic acid, and clopidogrel being the most commonly implicated drugs.

There has been a notable reduction in severe ADRs, such as fatal cerebral hemorrhages, due to improved management of oral anticoagulant therapy and better handling of adverse events related to heparin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to anticoagulants and to antiplatelet drugs recorded by the German spontaneous reporting system. Tiaden, JD., Wenzel, E., Berthold, HK., et al.[2022]

A safety analysis of ubrogepant and rimegepant, based on 2010 and 3691 adverse event reports respectively, identified 10 and 25 significant safety signals, indicating potential risks associated with these medications.

The adverse events reported were primarily related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious issues, highlighting the need for further research to confirm these safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System. Battini, V., Carnovale, C., Clementi, E., et al.[2023]

In a study of 56 patients with subarachnoid hemorrhages, internal hydrocephalus was most common in individuals aged 51-60, with varying severity: 39% low grade, 36% moderately severe, and 25% high grade.

Clinical symptoms related to hydrocephalus were observed in 59% of patients, and in 11% of cases, a Pudenz valve was implanted to manage the condition, indicating a significant intervention for those affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hydrocephalus following subarachnoid hemorrhage]. Danilewicz, B., Zwolińska, G., Jedlińska, M.[2016]

In a study of 109 patients with poor condition subarachnoid hemorrhage (SAH), tailored interventional approaches led to a reduced mortality rate of 21%, indicating that aggressive treatment can improve survival.

The study identified three distinct therapeutic strategies based on patient conditions, which resulted in favorable outcomes for 56% of patients, suggesting that adapting treatment to enhance cerebral perfusion is crucial for improving patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute management of poor condition subarachnoid hemorrhage patients. Eleftherios, A., Carvi y Nievas, MN.[2021]

In a study of 18 patients with perimesencephalic subarachnoid hemorrhage (PM SAH), long-term follow-up revealed that many experienced minor cognitive deficits, with 13 patients performing below the 10th percentile in at least one cognitive area.

High levels of depression were also common, as indicated by six patients scoring above 12 on the Hamilton Depression Rating Scale, suggesting that addressing depressive symptoms may be crucial for improving the long-term outcomes of these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and emotional consequences of perimesencephalic subarachnoid hemorrhage. Madureira, S., Canhão, P., Guerreiro, M., et al.[2019]

Short-term administration of epsilon aminocaproic acid (EACA) before early surgery in patients with aneurysmal subarachnoid hemorrhage (SAH) resulted in a low rehemorrhage rate of 1.4%, which is favorable compared to historical controls.

While EACA treatment showed promising results in reducing rehemorrhage, it was associated with a relatively high incidence of shunt-dependent hydrocephalus (42.3%), indicating a potential safety concern that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus. Harrigan, MR., Rajneesh, KF., Ardelt, AA., et al.[2013]

The study analyzed 345,662 spontaneous reports of adverse drug reactions (ADRs) submitted to the German Federal Institute for Drugs and Medical Devices, revealing a steady increase in reports since 1978, primarily due to stricter legal reporting requirements.

The most commonly reported ADRs were linked to drugs for nervous system disorders, with significant differences in reporting patterns between physicians and patients, suggesting a need for better patient education on potential ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. Dubrall, D., Schmid, M., Alešik, E., et al.[2023]

In a study of 27 patients with aneurysmal subarachnoid hemorrhage, oral administration of 60 mg nimodipine resulted in a statistically significant but clinically irrelevant drop in mean arterial blood pressure (MAP) and cerebral perfusion pressure (CPP), lasting for 120 minutes.

Despite the decrease in MAP and CPP after nimodipine administration, there were no significant changes in brain metabolism or cerebral metabolites, indicating that the effects on cerebral oxygenation may not be clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage. Moser, M., Schwarz, Y., Herta, J., et al.[2023]

In a rat model of subarachnoid hemorrhage (SAH), nimodipine effectively reduced cerebral vasospasm but did not improve long-term brain structure or cognitive function, indicating its limited efficacy in addressing the aftermath of SAH.

Deferoxamine, on the other hand, significantly reduced neuronal cell death and improved cognitive function, suggesting it may be a more effective treatment for mitigating the cognitive and structural damage associated with SAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of nimodipine and deferoxamine on brain injury in rat with subarachnoid hemorrhage. Qin, Y., Li, G., Sun, Z., et al.[2020]

In a study of 63 patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, those treated with phenylephrine (PE) were more likely to require a change to another vasopressor compared to those treated with norepinephrine (NE), indicating potential issues with PE's effectiveness.

Patients initially treated with PE had poorer neurological responses and were more likely to experience delayed infarcts, suggesting that NE may be a safer and more effective choice for managing induced hypertension in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Initial Vasopressors Used for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage. Roy, B., McCullough, LD., Dhar, R., et al.[2018]

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Deferiprone attenuates neuropathology and improves ...

Deferiprone treatment showed significant improvements in neurological severity scores, locomotor/gait performance and cognitive function, and attenuated ...

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Study on Deferiprone for Preventing Secondary ...

In this study, patients take Ferriprox daily for six months to see if it can help reduce iron accumulation in the brain after a stroke.

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Deferiprone for Subarachnoid Hemorrhage

The provided research does not contain specific safety data for Deferiprone or its use in treating subarachnoid hemorrhage. The studies focus on adverse events ...

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ahajournals.org

ahajournals.org/doi/10.1161/strokeaha.111.628032

Pilot Safety Trial of Deferiprone in 10 Subjects With ...

Deferiprone proved safe in this small population of superficial siderosis subjects. There was MRI evidence of reduced hemosiderin deposition with deferiprone.

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clinicaltrial.be/nl/details/66281?only_active=0&only_eligible=0&only_recruiting=0&per_page=100

Ferritin and Iron Burden in SAH sIRB - Klinische Studies...

The mean Ft level in subjects with aSAH without IVH was 900ng/ml vs. 420 ng/ml for those receiving deferiprone. The mean Ft level of patients with SAH and IVH ...