{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T13:05:17Z","timestamp":1783688717965,"version":"3.55.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["SVIN"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec id=\"svi212917-sec-0010\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">PP\u2010007 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\u2010007 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\u2010007 as an adjunctive treatment to mechanical thrombectomy (MT) in patients with stroke secondary to large vessel occlusion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"svi212917-sec-0020\" xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">HEMERA\u20101 (CarboxyHEMoglobin\u00a0OxygEn\u00a0delivery for\u00a0Revascularization in\u00a0Acute 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\u2010007 (320\u00a0mg\/kg: 30 min bolus followed by 2\u2010h 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"svi212917-sec-0030\" xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">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\u00a074.8\u00b112.7 years, 17.3\u00b14.2, and 7.9\u00b11.8, respectively.\u00a0Twelve patients were randomized to PP\u2010007 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\u201340 mm\u00a0Hg) during the bolus was observed in all PP\u2010007 patients without any clinical consequences. There were no other safety concerns.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"svi212917-sec-0040\" xml:lang=\"en\">\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p xml:lang=\"en\">No significant safety concerns were identified for the adjunctive use of PP\u2010007 in patients undergoing MT. (The study was funded by Prolong Pharmaceuticals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"svi212917-sec-0050\" xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT04677777.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/svin.123.001246","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T08:08:34Z","timestamp":1713859714000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["HEMERA 1 Carboxy\n            <u>HEM<\/u>\n            oglobin oxyg\n            <u>E<\/u>\n            n delivery for\n            <u>R<\/u>\n            evascularization in\n            <u>A<\/u>\n            cute Stroke: A Prospective, Randomized Phase\u00a01 Clinical Trial"],"prefix":"10.1161","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-4294","authenticated-orcid":false,"given":"Italo","family":"Linfante","sequence":"first","affiliation":[{"name":"Baptist Health S Florida","place":["Miami"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Clark","sequence":"additional","affiliation":[{"name":"Oregon Health and State University (OHSU) Medical Center","place":["Portland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo C.","family":"Haussen","sequence":"additional","affiliation":[{"name":"Grady Hospital","place":["Atlanta"]},{"name":"Emory University","place":["Atlanta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Hanel","sequence":"additional","affiliation":[{"name":"Baptist Hospital","place":["Jacksonville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rwoof","family":"Reshi","sequence":"additional","affiliation":[{"name":"University of Oklahoma","place":["Oklahoma City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme","family":"Dabus","sequence":"additional","affiliation":[{"name":"Baptist Health S Florida","place":["Miami"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Jubin","sequence":"additional","affiliation":[{"name":"Prolong Pharmaceuticals","place":["South Plainfield"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona P.","family":"Roshan","sequence":"additional","affiliation":[{"name":"Baptist Health S Florida","place":["Miami"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Star","family":"Belnap","sequence":"additional","affiliation":[{"name":"Baptist Health S Florida","place":["Miami"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh N.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Grotta","sequence":"additional","affiliation":[{"name":"Memorial Hermann Hospital","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wicks","sequence":"additional","affiliation":[{"name":"Baptist Health S Florida","place":["Miami"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn J.","family":"Cipolla","sequence":"additional","affiliation":[{"name":"University of Vermont Larner College of Medicine","place":["Burlington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Liebeskind","sequence":"additional","affiliation":[{"name":"University of California Los Angeles (UCLA) Los Angeles","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul G.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"University of Pittsburg Medical Center (UPMC)","place":["Pittsburg"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415061"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503780"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706442"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.07.002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000173403.60553.27"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.77"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/aor.12934"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/aor.13384"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01374.2005"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01079.2012"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17705567"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.526731"},{"key":"e_1_3_2_14_2","first-page":"1","article-title":"Toxicology and safety determination for a novel therapeutic dual carbon monoxide and oxygen delivery agent","volume":"4","author":"Misra H","year":"2014","unstructured":"Misra H, Kazo F, Newmark JA. Toxicology and safety determination for a novel therapeutic dual carbon monoxide and oxygen delivery agent. J Clin Toxicol. 2014;4:1\u201310.","journal-title":"J Clin Toxicol"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-017-0418-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjhh.2016.08.004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","DOI":"10.1111\/ctr.13155","article-title":"A phase Ib, open\u2010label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end\u2010stage renal disease","volume":"32","author":"Abu Jawdeh BG","year":"2018","unstructured":"Abu Jawdeh BG, Woodle ES, Leino AD, Brailey P, Tremblay S, Dorst T, Abdallah MH, Govil A, Byczkowski D, Misra H, et\u00a0al. A phase Ib, open\u2010label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end\u2010stage renal disease. Clin Transplant. 2018;32. doi: 10.1111\/ctr.13155","journal-title":"Clin Transplant"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70195-8"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01019-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"S178","DOI":"10.1212\/WNL.0000000000012809","article-title":"Linfante I. Collateral circulation augmentation and neuroprotection as adjuvant to mechanical thrombectomy in acute ischemic stroke","volume":"97","author":"Desai SM","year":"2021","unstructured":"Desai SM, Jha RM, Linfante I. Collateral circulation augmentation and neuroprotection as adjuvant to mechanical thrombectomy in acute ischemic stroke. Neurology. 2021;97:S178\u2010S184.","journal-title":"Neurology"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.559021"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1097\/MBC.0000000000000176","article-title":"Artifactual prolongation of activated partial thromboplastin time with PEGylated compounds in silica\u2010based assays","volume":"25","author":"Murphy B","year":"2014","unstructured":"Murphy B, Parrula MC, Perigard CJ, Li J. Artifactual prolongation of activated partial thromboplastin time with PEGylated compounds in silica\u2010based assays. Blood Coagul Fibrinolysis. 2014;25:876\u2013882.","journal-title":"Blood Coagul Fibrinolysis"}],"updated-by":[{"DOI":"10.1161\/svi2.13010","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000}}],"container-title":["Stroke: Vascular and Interventional Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/SVIN.123.001246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T11:28:35Z","timestamp":1747654115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/SVIN.123.001246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1161\/SVIN.123.001246"],"URL":"https:\/\/doi.org\/10.1161\/svin.123.001246","relation":{"correction":[{"id-type":"doi","id":"10.1161\/svi2.13010","asserted-by":"object"}]},"ISSN":["2694-5746"],"issn-type":[{"value":"2694-5746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2023-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e001246"}}