Trial Summary
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 assess the level of ferritin (Ft) in CSF (CSF withdrawn from ventriculostomy tube),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
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.
12345What 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.
678910Eligibility 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 am between 18 and 75 years old.
I was fully independent before my brain hemorrhage.
+8 more
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.
+19 more
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: DeferiproneExperimental Treatment2 Interventions
This is the drug arm (deferiprone). Patients will receive oral deferiprone
Group II: ControlPlacebo Group2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke University Health SystemDurham, NC
Univesity of Iowa Hospital and ClinicsIowa City, IA
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Who Is Running the Clinical Trial?
David HasanLead Sponsor
Duke UniversityLead Sponsor
References
Acute management of poor condition subarachnoid hemorrhage patients. [2021]Poor condition subarachnoid hemorrhage (SAH) patients present a high mortality and morbidity. In this study, we reviewed the acute interventional (surgical and endovascular) management of 109 SAH-poor condition patients, who were treated as early as logistically possible after confirming stable circulation parameters. Patients over the age of 70 years, without clinical response to painful stimulation were excluded. We recognized at least 3 different postinterventional therapeutic approaches: (1) Norm- or hypovolemic, normotensive hemodilution in 30 patients with space-occupying intracranial hematomas as well as in 31 cases with acute cerebro-spinal-fluid obstruction. (2) Normovolemic, hypertensive hemodilution after unilateral decompressive craniotomy in 23 surgical- and 2 endovascular-treated patients with focalized space occupying lesions and reduced cerebral perfusion. (3) Hypovolemic, normo-, or hypertensive hemodilution after bilateral decompressive craniotomy in 23 cases with massive brain-swelling. We observed a reduced mortality (21%). The overall late outcome was favorable in 56% and unfavorable in 23%. Selective aggressive treatment adapted to increase the cerebral perfusion, seems to be an effective therapy to improve the survival and outcome of several poor condition SAH-patients.
General recommendations for the management of aneurysmal subarachnoid hemorrhage. [2014]Subarachnoid hemorrhage is a neurologic emergency and a detrimental cerebrovascular event with a high rate of death and complications. Recommendations have been developed and based on literature search, evaluation of the results of large international clinical trials, collective experience of the authors, and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. The aim of these guidelines is to provide current and comprehensive recommendations and to assist physicians in making appropriate decisions in the management of subarachnoid hemorrhage. Evidence based information on the epidemiology, risk factors and prognosis, as well as recommendations on diagnostic work up, monitoring and management are provided, with regard to treatment possibilities in Croatia.
[Hydrocephalus following subarachnoid hemorrhage]. [2016]The authors present 56 patients with subarachnoid haemorrhages in whom CT of the head demonstrated internal hydrocephalus. This complication was observed most frequently in the age group 51-60 years. In 39% of cases hydrocephalus was low grade, in 36% it was moderately severe, and in 25% high grade. In 33 patients (59%) a syndrome of clinical symptoms and signs was observed which could be related, in part at least, to hydrocephalus. In 11% of cases. Pudenz valve had to be implanted. No significant differences were found in the frequency of hydrocephalus in late period after subarachnoid haemorrhage in relation to sex, number of haemorrhages, clinical state, vasospasm, treatment with epsilon-aminocaproic acid and dexamethasone.
Cognitive and emotional consequences of perimesencephalic subarachnoid hemorrhage. [2019]Little is known about the long-term cognitive-functional outcome of patients with perimesencephalic subarachnoid haemorrhage (PM SAH). We investigated the neurological, cognitive and emotional consequences of perimesencephalic subarachnoid haemorrhage in eighteen PM SAH patients admitted between November 1990 and July 1997 to the Neurology/Neurosurgery services of a University Hospital. The follow-up study consisted of a face-to-face interview, a neurological examination, an headache questionnaire, a neuropsychological evaluation (Mini-Mental State and a complementary battery to assess specific cognitive domains), the Hamilton Depression Rating Scale (HDRS) and the Blessed Dementia Scale. Thirteen patients performed below the 10th percentile in at least one cognitive domain. Six patients scored more than 12 points on the HDRS. Mini-Mental State and HDRS scores were moderately correlated (r = 0.55). Only three patients left their previous occupation. Minor cognitive deficits and high scores on a depression scale were frequent findings in this cohort of PM SAH patients. Reassurance and treatment of depressive symptoms could be important to improve the long-term outcome of PM SAH patients.
Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus. [2013]Long-term administration of the antifibrinolytic agent epsilon aminocaproic acid (EACA) reduces the rate of rehemorrhage in patients with aneurysmal subarachnoid hemorrhage (SAH), but is associated with cerebral ischemia.
Comparison of rates of reported adverse events associated with i.v. iron products in the United States. [2022]An analysis of reported adverse events (AEs) among patients using i.v. iron products, including the newer agent ferumoxytol, is presented.
Adverse reactions to anticoagulants and to antiplatelet drugs recorded by the German spontaneous reporting system. [2022]According to their code of professional conduct, German physicians are obliged to report suspected cases of adverse drug reactions (ADRs) to the Drug Commission of the German Medical Association (AkdA). On the basis of an agreement between the German Medical Association and the Federal Institute for Drugs and Medical Devices (BfArM) a common pharmacovigilance database within the German spontaneous reporting system was created. A user-friendly application program developed in-house enables the user to conduct searches about reported ADRs covering a wide variety of questions within a short period of time. ADRs caused by anticoagulants and by antiplatelet drugs still belong to the most reported adverse events. The most frequently reported suspected drugs are heparins, followed by ticlopidine, phenprocoumon, acetylsalicylic acid, and clopidogrel. Bleeding complications are the most often described ADR symptoms of any anticoagulation therapy, especially of phenprocoumon and acetylsalicylic acid. Another serious ADR is heparin-induced thrombocytopenia or changes in blood counts (CBC) due to ticlopidine and clopidogrel. During the past few years a reduction in severe reactions, such as cerebral hemorrhage, especially with fatal outcome was detectable because of better clinical management of oral anticoagulant therapy and of adverse events concerning heparin.
Frequent Adverse Drug Reactions, and Medication Groups under Suspicion. [2023]The adverse drug reaction database of the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) contains reports of suspected adverse drug reactions (ADRs) that are spon- taneously submitted by physicians, pharmacists, or patients. The aim of the present study was a descriptive analysis of all of these spontaneous reports.
Patients' experiences on adverse drug reactions reporting: a qualitative study. [2021]Spontaneous reporting of adverse drug reactions (ADRs) is an important source of information for post-marketing drug safety evaluation. Most countries have public access to reporting systems, but patients report only 3% of all ADRs. Little is known about factors affecting patient reporting. Our aim was to explore patients' experiences reporting ADRs and their views on the usability of the Canadian Vigilance reporting forms on MedEffect.
Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System. [2023]In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database registering spontaneous reports.
An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage. [2021]Introduction: Survival from aneurysmal subarachnoid hemorrhage has increased in the past few decades. However, functional outcome after subarachnoid hemorrhage is still suboptimal. Delayed cerebral ischemia (DCI) is one of the major causes of morbidity.Areas covered: Mechanisms underlying vasospasm and DCI after aneurysmal subarachnoid hemorrhage and pharmacological treatment are summarized in this review.Expert opinion: Oral nimodine, an L-type dihydropyridine calcium channel blocker, is the only FDA-approved drug for the prevention and treatment of neurological deficits after aneurysmal subarachnoid hemorrhage. Fasudil, a potent Rho-kinase inhibitor, has also been shown to improve the clinical outcome and has been approved in some countries for use in patients with aneurysmal subarachnoid hemorrhage. Although other drugs, including nicardipine, cilostazol, statins, clazosentan, magnesium and heparin, have been expected to have beneficial effects on DCI, there has been no convincing evidence supporting the routine use of those drugs in patients with aneurysmal subarachnoid hemorrhage in clinical practice. Further elucidation of the mechanisms underlying DCI and the development of effective therapeutic strategies for DCI, including combination therapy, are necessary to further improve the functional outcome and mortality after subarachnoid hemorrhage.
[Experience with nimodipine treatment of vascular spasm after subarachnoid hemorrhage]. [2013]Pathogenesis of vasospasms following subarachnoid haemorrhage and possible therapeutic efficacy of nimodipine (calcium channel blocking agent) are discussed. The authors present their own experience in the treatment of 209 patients with subarachnoid haemorrhage with nimodipine. Collected clinical results suggest the necessity of the combined treatment of vasospasm following subarachnoid haemorrhage with nimodipine, hypervolemia, and hypertensive agents.
The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage. [2023]Nimodipine is routinely administered to aneurysmal subarachnoid hemorrhage patients to improve functional outcomes. Nimodipine can induce marked systemic hypotension, which might impair cerebral perfusion and brain metabolism.
Comparison of the effects of nimodipine and deferoxamine on brain injury in rat with subarachnoid hemorrhage. [2020]Subarachnoid hemorrhage (SAH) may lead to brain atrophy and cognitive dysfunction. This study aimed to compare the efficacy of nimodipine and deferoxamine on these sequelae of SAH. A rat model of SAH was established by the double-hemorrhage method. These rats were injected with saline (intraperitoneal, IP), nimodipine (IP), or deferoxamine (IP and intranasal) every 12 h for 5 days after SAH. The MRI scanning, including magnetic resonance angiography, diffusion tensor imaging, T2-weighted imaging, was performed to detect the brain structure. The levels of iron metabolism-related proteins were examined by Western blot analysis. The Morris water maze (MWM) test was used to assess the cognitive function. Then, then neurons in the cortex and hippocampus were counted on hematoxylin and eosin-stained brain sections. Significant cerebral vasospasm (CVS) was found in the saline and deferoxamine groups, but not in the nimodipine group. Cerebral peduncle injury was detected in the saline and nimodipine groups, but not significantly in the deferoxamine group. Compared with nimodipine, deferoxamine reduced transferrin (Tf), Tf receptor, and ferritin levels after SAH. The MWM performances were significantly worse in the saline and nimodipine groups than that in the deferoxamine group. Brain atrophy and neuronal losses were more significant in the saline and nimodipine groups than in the deferoxamine group. Nimodipine significantly ameliorated CVS, but it did not improve the late changes in brain structure and cognitive function. Deferoxamine effectively reduced neuronal cell death and ameliorated cognitive function after SAH.
Comparison of Initial Vasopressors Used for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage. [2018]The main reason for morbidity after aneurysmal subarachnoid hemorrhage (aSAH) is delayed cerebral ischemia (DCI). The mainstay of medical therapy for treating DCI is induced hypertension with vasopressors to restore cerebral perfusion. Both phenylephrine (PE) and norepinephrine (NE) are commonly used for induced hypertension, but the impact of the initial choice of vasopressor on the efficacy, adverse effects, or outcome after hemodynamic therapy for DCI is unknown.