447 Haptoglobin Treatment to Improve Outcome After Aneurysmal Subarachnoid Haemorrhage: A Consensus Perspective on Clinical Translation

Abstract

Abstract Aim Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of stroke with an unmet need to improve outcome. This study focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress and arriving at a Delphi-based global consensus regarding the role of extracellular haemoglobin and research priorities for clinical translation of haemoglobin-scavenging strategies. Method A narrative review of the topic by searching PubMed with relevant keywords and through discussions with leading expert in the field of aSAH. A modified Delphi processes. Four virtual meetings were held, two prior to starting, and two during the first round. Otherwise, the study was conducted electronically. Results Clinicians (n = 72) and scientific experts (n = 28) from five continents participated in the Delphi study. Microvascular spasm, iInflammation, microvascular spasm, and initial intracranial pressure rise were deemed the most important pathophysiological pathways determining outcome. Extracellular haemoglobin was thought to play an important role mostly in iron toxicity, oxidative stress, nitric oxide homeostasis and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field to be ready for early phase trial. The highest priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics and outcome measure selection. Conclusions These results highlight the pressing need for early phase trials of intracranial haptoglobin for aSAH, and the immense value of early input from clinical disciplines on a global scale during the early stages of clinical translation.