Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial

Abstract

Rationale: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding and cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests inflammation contributes to delayed cerebral ischemia and poor out-come in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. Aim: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically rele-vant endpoint in SAH patients. Methods and design: FINISHER is a multicentre, prospective, randomized, double-blinded, place-bo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. Sample size estimates: 334 patients will be randomized to either dexamethasone or placebo within 48h after SAH. The dexamethasone dose is 8mg tds days 1-7 and then 8mg od for days 8-21 Study outcome: The primary outcome is the modified Rankin Scale (mRS) at 6 months which is dichotomized to favourable (mRS 0-3) versus unfavourable (mRS 4-6). Discussion: The results of this study will provide the first phase III evidence as to whether dexame-thasone improves outcome in SAH. Trial registration: ClinicalTrials.gov NCT05132920. EudraCT Number 2021-000732-54.

Risk factors for poor outcome after aneurysmal subarachnoid hemorrhage in patients with initial favorable neurological status

“…However, lower rate of pathologic ICP increase, more frequent utilization of intra-arterial spasmolysis for vasospasm treatment, and somewhat decreasing rate of systemic infections in the cohort during the study period might have contributed to better final outcome of our aSAH patients. As possible explanation for this lower burden of ICP and infection-related complications, changes in the conservative SAH management [ 3 ], and particularly the gradual reduction in the practice of using triple H therapy [ 14 ] should be mentioned. Fittingly, there was more frequent use of intra-arterial spasmolysis for vasospasm treatment in the investigated cohort during this time.…”

Morphometric Study of the Initial Ventricular Indices to Predict the Complications and Outcome of Aneurysmal Subarachnoid Hemorrhage

“…The first studies analyzing inflammation after SAH have attempted to identify a link between inflammation and the risk of cerebral vasospasm [ 26 , 27 ]. Recent studies also identified a higher risk of DCI with increasing inflammatory response after SAH [ 28 , 29 ]. However, this association is probably due to the involvement of inflammatory mediators in the coagulation cascades, resulting in microthrombosis and microcirculatory disturbances, and accordingly, a higher risk of DCI, rather being than related to the vasospasm of large intracranial vessels [ 30 ].…”

“…Moreover, the increased downregulation of inflammatory cytokines by continuous dexamethasone administration can also contribute to the prevention of secondary SAH complications such as DCI. To assess the above-mentioned results and other potential mechanisms of the glucocorticoids effect, the organizers of a multi-center prospective trial analyzing the effect of treatment with dexamethasone on the SAH outcome are currently recruiting patients in Germany [ 29 ].…”

Systematic assessment of early brain injury severity at admission with aneurysmal subarachnoid hemorrhage

“…Even a prophylactic DHC could potentially be beneficial 19 . Jabbarli The establishment of an EBI severity grading may also be helpful for a more reliable patient 14 selection as an inclusion criterion in studies evaluating therapies for EBI not only surgical but also medical treatments such as anti-inflammatory agents, which is the objective of the currently ongoing FINISHER trial 22 .…”