HEMERA 1 CarboxyHEMoglobin oxygEn delivery for Revascularization in Acute Stroke: A Prospective, Randomized Phase 1 Clinical Trial.

Background: PP-007 is a polyethylene glycol (PEG)ylated bovine carboxyhemoglobin gas transfer molecule with pleotropic cytoprotective effects, vasodilatation, plasma expansion, and optimization of oxygen delivery. Rodent middle cerebral artery occlusion models have demonstrated that PP-007 increases blood flow in the collateral circulation and reduces final infarct volumes, supporting a potential role as neuroprotective agent in acute ischemic stroke. We aim to evaluate the safety and feasibility of PP-007 as an adjunctive treatment to mechanical thrombectomy (MT) in patients with stroke secondary to large vessel occlusion. Methods: HEMERA-1 (CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke) was a multicenter, prospective, randomized, controlled phase 1 clinical trial. Anterior circulation large vessel occlusion patients were assigned in a 3:1 ratio to receive either PP-007 (320 mg/kg: 30 min bolus followed by 2-h infusion) plus MT or MT alone within 24 hours after symptom onset. Comprehensive safety evaluation was performed by independent Data Monitoring Safety Board and Imaging Core Lab. Results: From October 1, 2021 to June 30, 2022, a total of 17 patients were recruited. Age, baseline National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT Score were 74.8±12.7 years, 17.3±4.2, and 7.9±1.8, respectively. Twelve patients were randomized to PP-007 plus MT, 1 was randomized but not treated, 4 patients were randomized to MT alone. Recanalization of the occluded vessel was achieved in all patients. A transient systolic blood pressure increase (20-40 mm Hg) during the bolus was observed in all PP-007 patients without any clinical consequences. There were no other safety concerns. Conclusion: No significant safety concerns were identified for the adjunctive use of PP-007 in patients undergoing MT. (The study was funded by Prolong Pharmaceuticals. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04677777.