Active clinical trials for "Subarachnoid Hemorrhage"

The pathophysiological mechanisms of aneurysmal subarachnoid haemorrhage (aSAH) involve early brain injury (EBI) and delayed cerebral ischemia (DCI). Several mechanisms contribute to EBI pathogenesis, including cell death, inflammatory response, oxidative stress, excitotoxicity, microcirculatory dysfunction, microthrombosis and cortical spreading depolarization. All are suggested to be linked due to common pathogenic pathways and direct interaction. Despite advances in research of diagnostics and treatment strategies, brain injury remains the major cause of death and disability in SAH patients. There is no sufficient treatment of SAH and its devastating consequences known so far. Developing and improving diagnostic methods to monitor SAH patients and to evaluate efficacy of treatment strategies are essential in SAH research. These include neuroimaging, biomarkers, and other parameters such as invasive multimodal neuromonitoring and intraoperative electrophysiological monitoring. Cerebral vasospasm (CV) - mostly responsible for DCI - can be depicted on angiograms. Altogether, tremendous efforts have been taken to conquer the occurrence and sustainability of CV. The mortality of patients suffering aSAH rises up to 50% if the patients' condition is critical (Hunt&Hess (HH) Grade 5, WFNS Grade 5, modified Fisher Grade 4). Reports of beneficial outcome in patients with pre-existing CSF shunting have been published. The hypothesis of early CSF reapplication to the bloodstream, in order to prevent CV seems to be positively approved by the mentioned reports. Nevertheless, no data could be found on the mechanisms of action in this phenomenon. To confirm the presence of interaction of the mechanisms of EBI and evaluate the application of cerebrospinal fluid (CSF), a pilot clinical trial was planned. Due to the lack of validated animal models for aSAH it is necessary to perform the trial first-in-human. A pilot (proof of concept) trial - is done through inclusion of 10 patients with severe aSAH (≥HH4). According to clinical guidelines, these patients receive external ventricular drainages in order to drain CSF and lower intracranial pressure. An interim analysis of data will be performed after inclusion and treatment of 5 patients. Blood-/CSF-sampling for further analysis will be collected before, during and after treatment according to the study protocol.

At present, cerebral vasospasm (cVS) is the main cause of delayed cerebral infarction (DCI), which leads to high disability and mortality rate after aneurysmal subarachnoid hemorrhage. As a consequence, the key of reducing DCI is to prevent cVS. But unfortunately, despite years of efforts, the prevention and treatment of cVS is still a major clinical dilemma and various ways of treatment are still being explored. Recent studies have shown that stellate ganglion block (SGB) can dilate cerebral vessels and alleviate the impact of existing cVS. However, there is no study to evaluate the effect of early application of SGB on the improvement and prevention of cVS after aSAH.

The investigators seek to demonstrate that the combined use of cilostazol and nimodipine will significantly decrease the rate of delayed cerebral infarction and cerebral vasospasm after cerebrovascular intervention when compared to nimodipine alone.

Patients with subarachnoid hemorrhage are prone to suffer from dysnatriemia. Evidence shows that hyponatriemia is associated with increased incidence of vasospasm, brain swelling and mortality in these patients. Patients with subarachnoid hemorrhage often require large amounts of iv fluids in order to maintain euvolemia and support cardiocirculatory function. Prior evidence shows that the type of infusion fluid significantly influences blood sodium content. Hence, this study evaluated whether the sodium content of the infusion solution impacts mortality and morbidity in patients with subarachnoid hemorrhage.

The aim of this study is to evaluate the effect of inhalational sedation on cerebral perfusion in patients with SAH. It will evaluate whether the administration of isofluorane, by inducing direct vasodilation in the cerebral parenchyma, can improve the cerebral perfusion rates. Perfusional CT will be used to study the variation of cerebral blood flow to rule out the vasodilatory effect on territories with different cerebrovascular reactivity aggravating the phenomena of distrectual hypoperfusion (theft theory).

Introduction Patients with severe brain injury are often restricted to bed rest during the early period of brain injury which may lead to unwanted secondary complications. There is lack of evidence of when to initiate the first mobilisation. The Sara Combilizer® is an easy and efficient tool for mobilising patients with severe injuries, including brain injury. Through a randomised cross-over trial the investigators will investigate the impact of early mobilisation on patients with severe acquired brain injury caused by traumatic brain injury, subarachnoid brain injury or intracranial haematoma. The investigators hypothesise that mobilisation using the Sara Combilizer® does not affect partial oxygenation of brain tissue.

With evolving endovascular technologies there is a growing debate centered on the relative safety and efficacy of the currently accepted alternatives for the treatment of ruptured cerebral aneurysms in the face of acute subarachnoid hemorrhage (SAH). The purpose of this study is to compare the safety and efficacy of microsurgical clipping and endovascular coiling of acutely ruptured cerebral aneurysms in a prospective, randomized fashion.

Previous work has demonstrated patients presenting with ruptured aneurysms that develop radiographic and clinical vasospasm have a higher permeability of the blood brain membrane. Matrix metalloproteinase 9 (MMP9) has been studied and recently implicated in both the pathogenesis of the blood brain barrier breakdown and vasogenic edema of ischemia strokes, and is suggested to be an accurate biomarker to predict the onset of cerebral vasospasm after subarachnoid hemorrhage. The therapeutic benefit of minocycline, an MMP9 inhibitor, has been investigated in ischemic stroke population, however its role in the treatment of cerebral vasospasm from ruptured aneurysms remains unknown. Our project has two main goals: to further confirm MMP9 has a reliable biomarker for the onset of cerebral vasospasm, and secondarily to investigate any possible therapeutic benefit that minocycline has in the vasospasm population. Vasospasm continues to be one of the major contributors of morbidity and mortality in the ruptured aneurysm population, and close monitoring of the neurologic exam during the 'vasospasm window' usually requires two weeks in the intensive care unit in most academic settings. As such, if we are better able to predict which patients are at risk of developing vasospasm based on MMP9 levels, we will be better able to anticipate the need for intervention and therefore mitigate the risk of vasospasm induced ischemic strokes, ultimately resulting in better outcomes in the ruptured aneurysm population. Further, if we are able to identify minocycline as a therapeutic agent to deter, or lessen the severity of vasospasm, we can possibly improve neurologic outcomes, decrease hospital stays, ultimately providing an improved and more cost-effective treatment strategy to our patients.

This phase III trial will establish whether IL-1Ra, with sub-cutaneous (SC) administration twice daily for up to 21 days post aneurysmal subarachnoid haemorrhage (aSAH), improves clinical outcome as measured by ordinal shift in mRS at 6 months. Patients with SAH transferred to a neurosurgical centre will be identified and approached for study participation. Following consent, patients will be randomised to receive either IL-1Ra or placebo for a maximum of 21 days from onset of symptoms. Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment. Blood samples for plasma IL-6 will be obtained prior to randomisation and at day 3-5 post randomisation for IL-6 & IL-1 measurement. Safety will be measured at 30 days post randomisation and outcome assessed at 6 months post randomisation.

The objective of this study is to determine whether acetaminophen (APAP), N-acetylcysteine (NAC), and APAP in combination with NAC will inhibit lipid peroxidation in aneurysmal subarachnoid hemorrhage (aSAH), utilizing F2-IsoPs as biomarkers for lipid peroxidation.