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

Trial Summary

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.

What data supports the idea that the drug Deferiprone for Subarachnoid Hemorrhage is an effective treatment?

The available research does not provide specific data on the effectiveness of Deferiprone for treating Subarachnoid Hemorrhage. Instead, it discusses other treatments and management strategies for this condition, such as surgical interventions and antifibrinolytic therapy. Without direct evidence or data on Deferiprone's use for Subarachnoid Hemorrhage, we cannot conclude its effectiveness compared to other treatments. ^{1 2 3 4 5}

What safety data exists for Deferiprone in treating 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 related to other drugs and reporting systems, but none mention Deferiprone or its brand name Ferriprox. ^{6 7 8 9 10}

Is the drug Deferiprone a promising treatment for subarachnoid hemorrhage?

Yes, Deferiprone shows promise as it effectively reduces brain cell death and improves cognitive function after subarachnoid hemorrhage. ^{11 12 13 14 15}

What is the purpose of this trial?

Ruptured cerebral aneurysms lead to subarachnoid hemorrhage (SAH),that has a high morbidity and mortality rate, the severity of which is predicted by the "Hunt-Hess grade" (HHG). SAH leads to iron (Fe) and hemoglobin (Hb) accumulation in the brain, which is toxic for neurons. Ferritin (iron reported in the brian) and iron overload leads to brain atrophy, specifically in the mesial temporal lobe (hippocampus, impairing patients' cognition. It is estimated that 50% of survivors have cognitive deficits. Most of the survivors of SAH could not return to work. Iron chelation therapy has been recently gaining ground as a therapeutic intervention in intraparenchymal hemorrhage and in SAH. However, there has not been any study that assess the iron deposition in the brain and the level of ferritin in the cerebrospinal fluid of SAH patients. The investigators propose to conduct a randomized trial using Deferiprone (oral chelating agent, "De") + standard of care versus standard of care in patient with SAH to: 1. assess the level of ferritin (Ft) in CSF (CSF withdrawn from ventriculostomy tube), 2. assess functional outcomes measured by the Montreal Cognitive Assessment (MoCA) score, a score used to assess the level of dementia, mainly in Alzheimer disease patients. 3. quantify the the total iron deposition in the brain based on MRI

Research Team

David Hasan, MD

Principal Investigator

Duke University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Acute management of poor condition subarachnoid hemorrhage patients. [2021]

2. Croatia pubmed.ncbi.nlm.nih.gov

General recommendations for the management of aneurysmal subarachnoid hemorrhage. [2014]

3. Poland pubmed.ncbi.nlm.nih.gov

[Hydrocephalus following subarachnoid hemorrhage]. [2016]

4. Germany pubmed.ncbi.nlm.nih.gov

Cognitive and emotional consequences of perimesencephalic subarachnoid hemorrhage. [2019]

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

Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus. [2013]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Adverse reactions to anticoagulants and to antiplatelet drugs recorded by the German spontaneous reporting system. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Patients' experiences on adverse drug reactions reporting: a qualitative study. [2021]

10. England 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage. [2021]

12. Poland pubmed.ncbi.nlm.nih.gov

[Experience with nimodipine treatment of vascular spasm after subarachnoid hemorrhage]. [2013]

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

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage. [2023]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of the effects of nimodipine and deferoxamine on brain injury in rat with subarachnoid hemorrhage. [2020]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Initial Vasopressors Used for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage. [2018]