Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
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Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial. / Poli, Sven; Mbroh, Joshua; Baron, Jean-Claude; Singhal, Aneesh B; Strbian, Daniel; Molina, Carlos; Lemmens, Robin; Turc, Guillaume; Mikulik, Robert; Michel, Patrik; Tatlisumak, Turgut; Audebert, Heinrich J; Dichgans, Martin; Veltkamp, Roland; Hüsing, Johannes; Graessner, Holm; Fiehler, Jens; Montaner, Joan; Adeyemi, Adedolapo Kamaldeen; Althaus, Katharina; Arenillas, Juan F; Bender, Benjamin; Benedikt, Frank; Broocks, Gabriel; Burghaus, Ina; Cardona, Pere; Deb-Chatterji, Milani; Cviková, Martina; Defreyne, Luc; De Herdt, Veerle; Detante, Olivier; Ernemann, Ulrike; Flottmann, Fabian; García Guillamón, Lídia; Glauch, Monika; Gomez-Exposito, Alexandra; Gory, Benjamin; Sylvie Grand, Sylvie; Haršány, Michal; Hauser, Till Karsten; Heck, Olivier; Hemelsoet, Dimitri; Hennersdorf, Florian; Hoppe, Julia; Kalmbach, Pia; Kellert, Lars; Köhrmann, Martin; Kowarik, Markus; Lara-Rodríguez, Blanca; Legris, Loic; Lindig, Tobias; Luntz, Steffen; Lusk, Jay; Mac Grory, Brian; Manger, Andreas; Martinez-Majander, Nicolas; Mengel, Annerose; Meyne, Johannes; Müller, Susanne; Mundiyanapurath, Sibu; Naggara, Olivier; Nedeltchev, Krassen; Nguyen, Thanh N; Nilsson, Maike A; Obadia, Michael; Poli, Khouloud; Purrucker, Jan C; Räty, Silja; Richard, Sebastien; Richter, Hardy; Schilte, Clotilde; Schlemm, Eckhard; Stöhr, Linda; Stolte, Benjamin; Sykora, Marek; Thomalla, Götz; Tomppo, Liisa; van Horn, Noel; Zeller, Julia; Ziemann, Ulf; Zuern, Christine S; Härtig, Florian; Tuennerhoff, Johannes; PROOF investigators.
in: INT J STROKE, Jahrgang 19, Nr. 1, 01.2024, S. 120-126.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
AU - Poli, Sven
AU - Mbroh, Joshua
AU - Baron, Jean-Claude
AU - Singhal, Aneesh B
AU - Strbian, Daniel
AU - Molina, Carlos
AU - Lemmens, Robin
AU - Turc, Guillaume
AU - Mikulik, Robert
AU - Michel, Patrik
AU - Tatlisumak, Turgut
AU - Audebert, Heinrich J
AU - Dichgans, Martin
AU - Veltkamp, Roland
AU - Hüsing, Johannes
AU - Graessner, Holm
AU - Fiehler, Jens
AU - Montaner, Joan
AU - Adeyemi, Adedolapo Kamaldeen
AU - Althaus, Katharina
AU - Arenillas, Juan F
AU - Bender, Benjamin
AU - Benedikt, Frank
AU - Broocks, Gabriel
AU - Burghaus, Ina
AU - Cardona, Pere
AU - Deb-Chatterji, Milani
AU - Cviková, Martina
AU - Defreyne, Luc
AU - De Herdt, Veerle
AU - Detante, Olivier
AU - Ernemann, Ulrike
AU - Flottmann, Fabian
AU - García Guillamón, Lídia
AU - Glauch, Monika
AU - Gomez-Exposito, Alexandra
AU - Gory, Benjamin
AU - Sylvie Grand, Sylvie
AU - Haršány, Michal
AU - Hauser, Till Karsten
AU - Heck, Olivier
AU - Hemelsoet, Dimitri
AU - Hennersdorf, Florian
AU - Hoppe, Julia
AU - Kalmbach, Pia
AU - Kellert, Lars
AU - Köhrmann, Martin
AU - Kowarik, Markus
AU - Lara-Rodríguez, Blanca
AU - Legris, Loic
AU - Lindig, Tobias
AU - Luntz, Steffen
AU - Lusk, Jay
AU - Mac Grory, Brian
AU - Manger, Andreas
AU - Martinez-Majander, Nicolas
AU - Mengel, Annerose
AU - Meyne, Johannes
AU - Müller, Susanne
AU - Mundiyanapurath, Sibu
AU - Naggara, Olivier
AU - Nedeltchev, Krassen
AU - Nguyen, Thanh N
AU - Nilsson, Maike A
AU - Obadia, Michael
AU - Poli, Khouloud
AU - Purrucker, Jan C
AU - Räty, Silja
AU - Richard, Sebastien
AU - Richter, Hardy
AU - Schilte, Clotilde
AU - Schlemm, Eckhard
AU - Stöhr, Linda
AU - Stolte, Benjamin
AU - Sykora, Marek
AU - Thomalla, Götz
AU - Tomppo, Liisa
AU - van Horn, Noel
AU - Zeller, Julia
AU - Ziemann, Ulf
AU - Zuern, Christine S
AU - Härtig, Florian
AU - Tuennerhoff, Johannes
AU - PROOF investigators
PY - 2024/1
Y1 - 2024/1
N2 - RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
AB - RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
U2 - 10.1177/17474930231185275
DO - 10.1177/17474930231185275
M3 - SCORING: Journal article
C2 - 37515459
VL - 19
SP - 120
EP - 126
JO - INT J STROKE
JF - INT J STROKE
SN - 1747-4930
IS - 1
ER -