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, Joshua MBROH, Jean-Claude BARON, Aneesh B SINGHAL, Daniel STRBIAN et. al.
Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
Authors
POLI, Sven, Joshua MBROH, Jean-Claude BARON, Aneesh B SINGHAL, Daniel STRBIAN, Carlos MOLINA, Robin LEMMENS, Guillaume TURC, Robert MIKULÍK (203 Czech Republic, guarantor, belonging to the institution), Patrik MICHEL, Turgut TATLISUMAK, Heinrich J AUDEBERT, Martin DICHGANS, Roland VELTKAMP, Johannes HUESING, Holm GRAESSNER, Jens FIEHLER, Joan MONTANER, Adedolapo Kamaldeen ADEYEMI, Katharina ALTHAUS, Juan F ARENILLAS, Benjamin BENDER, Frank BENEDIKT, Gabriel BROOCKS, Ina BURGHAUS, Pere CARDONA, Milani DEB-CHATTERJI, Martina CVIKOVÁ (703 Slovakia, belonging to the institution), Luc DEFREYNE, De Herdt VEERLE, Olivier DETANTE, Ulrike ERNEMANN, Fabian FLOTTMANN, Lidia Garcia GUILLAMON, Monika GLAUCH, Alexandra GOMEZ-EXPOSITO, Benjamin GORY, Sylvie Sylvie GRAND, Michal HARŠÁNY (703 Slovakia, belonging to the institution), Till Karsten HAUSER, Olivier HECK, Dimitri HEMELSOET, Florian HENNERSDORF, Julia HOPPE, Pia KALMBACH, Lars KELLERT, Martin KOHRMANN, Markus KOWARIK, Blanca LARA-RODRIGUEZ, Loic LEGRIS, Tobias LINDIG, Steffen LUNTZ, Jay LUSK, Mac Grory BRIAN, Andreas MANGER, Nicolas MARTINEZ-MAJANDER, Annerose MENGEL, Johannes MEYNE, Susanne MULLER, Sibu MUNDIYANAPURATH, Olivier NAGGARA, Krassen NEDELTCHEV, Thanh N NGUYEN, Maike A NILSSON, Michael OBADIA, Khouloud POLI, Jan C PURRUCKER, Silja RATY, Sebastien RICHARD, Hardy RICHTER, Clotilde SCHILTE, Eckhard SCHLEMM, Linda STOHR, Benjamin STOLTE, Marek SYKORA, Goetz THOMALLA, Liisa TOMPPO, van Horn NOEL, Julia ZELLER, Ulf ZIEMANN, Christine S ZUERN, Florian HARTIG and Johannes TUENNERHOFF
Edition
International Journal of Stroke, LONDON, SAGE PUBLICATIONS LTD, 2024, 1747-4930
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.
POLI, Sven, Joshua MBROH, Jean-Claude BARON, Aneesh B SINGHAL, Daniel STRBIAN, Carlos MOLINA, Robin LEMMENS, Guillaume TURC, Robert MIKULÍK, Patrik MICHEL, Turgut TATLISUMAK, Heinrich J AUDEBERT, Martin DICHGANS, Roland VELTKAMP, Johannes HUESING, Holm GRAESSNER, Jens FIEHLER, Joan MONTANER, Adedolapo Kamaldeen ADEYEMI, Katharina ALTHAUS, Juan F ARENILLAS, Benjamin BENDER, Frank BENEDIKT, Gabriel BROOCKS, Ina BURGHAUS, Pere CARDONA, Milani DEB-CHATTERJI, Martina CVIKOVÁ, Luc DEFREYNE, De Herdt VEERLE, Olivier DETANTE, Ulrike ERNEMANN, Fabian FLOTTMANN, Lidia Garcia GUILLAMON, Monika GLAUCH, Alexandra GOMEZ-EXPOSITO, Benjamin GORY, Sylvie Sylvie GRAND, Michal HARŠÁNY, Till Karsten HAUSER, Olivier HECK, Dimitri HEMELSOET, Florian HENNERSDORF, Julia HOPPE, Pia KALMBACH, Lars KELLERT, Martin KOHRMANN, Markus KOWARIK, Blanca LARA-RODRIGUEZ, Loic LEGRIS, Tobias LINDIG, Steffen LUNTZ, Jay LUSK, Mac Grory BRIAN, Andreas MANGER, Nicolas MARTINEZ-MAJANDER, Annerose MENGEL, Johannes MEYNE, Susanne MULLER, Sibu MUNDIYANAPURATH, Olivier NAGGARA, Krassen NEDELTCHEV, Thanh N NGUYEN, Maike A NILSSON, Michael OBADIA, Khouloud POLI, Jan C PURRUCKER, Silja RATY, Sebastien RICHARD, Hardy RICHTER, Clotilde SCHILTE, Eckhard SCHLEMM, Linda STOHR, Benjamin STOLTE, Marek SYKORA, Goetz THOMALLA, Liisa TOMPPO, van Horn NOEL, Julia ZELLER, Ulf ZIEMANN, Christine S ZUERN, Florian HARTIG and Johannes TUENNERHOFF. Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial. International Journal of Stroke. LONDON: SAGE PUBLICATIONS LTD, 2024, vol. 19, No 1, p. 120-126. ISSN 1747-4930. Available from: https://dx.doi.org/10.1177/17474930231185275.
@article{2327103, author = {Poli, Sven and Mbroh, Joshua and Baron, JeanandClaude and Singhal, Aneesh B and Strbian, Daniel and Molina, Carlos and Lemmens, Robin and Turc, Guillaume and Mikulík, Robert and Michel, Patrik and Tatlisumak, Turgut and Audebert, Heinrich J and Dichgans, Martin and Veltkamp, Roland and Huesing, Johannes and Graessner, Holm and Fiehler, Jens and Montaner, Joan and Adeyemi, Adedolapo Kamaldeen and Althaus, Katharina and Arenillas, Juan F and Bender, Benjamin and Benedikt, Frank and Broocks, Gabriel and Burghaus, Ina and Cardona, Pere and DebandChatterji, Milani and Cviková, Martina and Defreyne, Luc and Veerle, De Herdt and Detante, Olivier and Ernemann, Ulrike and Flottmann, Fabian and Guillamon, Lidia Garcia and Glauch, Monika and GomezandExposito, Alexandra and Gory, Benjamin and Grand, Sylvie Sylvie and Haršány, Michal and Hauser, Till Karsten and Heck, Olivier and Hemelsoet, Dimitri and Hennersdorf, Florian and Hoppe, Julia and Kalmbach, Pia and Kellert, Lars and Kohrmann, Martin and Kowarik, Markus and LaraandRodriguez, Blanca and Legris, Loic and Lindig, Tobias and Luntz, Steffen and Lusk, Jay and Brian, Mac Grory and Manger, Andreas and MartinezandMajander, Nicolas and Mengel, Annerose and Meyne, Johannes and Muller, Susanne and Mundiyanapurath, Sibu and Naggara, Olivier and Nedeltchev, Krassen and Nguyen, Thanh N and Nilsson, Maike A and Obadia, Michael and Poli, Khouloud and Purrucker, Jan C and Raty, Silja and Richard, Sebastien and Richter, Hardy and Schilte, Clotilde and Schlemm, Eckhard and Stohr, Linda and Stolte, Benjamin and Sykora, Marek and Thomalla, Goetz and Tomppo, Liisa and Noel, van Horn and Zeller, Julia and Ziemann, Ulf and Zuern, Christine S and Hartig, Florian and Tuennerhoff, Johannes}, article_location = {LONDON}, article_number = {1}, doi = {http://dx.doi.org/10.1177/17474930231185275}, keywords = {Normobaric oxygen therapy; NBO; hyperoxygenation; neuroprotection; penumbra; ischemic stroke; thrombectomy}, language = {eng}, issn = {1747-4930}, journal = {International Journal of Stroke}, title = {Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial}, url = {https://journals.sagepub.com/doi/10.1177/17474930231185275}, volume = {19}, year = {2024} }
TY - JOUR ID - 2327103 AU - Poli, Sven - Mbroh, Joshua - Baron, Jean-Claude - Singhal, Aneesh B - Strbian, Daniel - Molina, Carlos - Lemmens, Robin - Turc, Guillaume - Mikulík, Robert - Michel, Patrik - Tatlisumak, Turgut - Audebert, Heinrich J - Dichgans, Martin - Veltkamp, Roland - Huesing, 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 - Veerle, De Herdt - Detante, Olivier - Ernemann, Ulrike - Flottmann, Fabian - Guillamon, Lidia Garcia - Glauch, Monika - Gomez-Exposito, Alexandra - Gory, Benjamin - Grand, Sylvie Sylvie - Haršány, Michal - Hauser, Till Karsten - Heck, Olivier - Hemelsoet, Dimitri - Hennersdorf, Florian - Hoppe, Julia - Kalmbach, Pia - Kellert, Lars - Kohrmann, Martin - Kowarik, Markus - Lara-Rodriguez, Blanca - Legris, Loic - Lindig, Tobias - Luntz, Steffen - Lusk, Jay - Brian, Mac Grory - Manger, Andreas - Martinez-Majander, Nicolas - Mengel, Annerose - Meyne, Johannes - Muller, Susanne - Mundiyanapurath, Sibu - Naggara, Olivier - Nedeltchev, Krassen - Nguyen, Thanh N - Nilsson, Maike A - Obadia, Michael - Poli, Khouloud - Purrucker, Jan C - Raty, Silja - Richard, Sebastien - Richter, Hardy - Schilte, Clotilde - Schlemm, Eckhard - Stohr, Linda - Stolte, Benjamin - Sykora, Marek - Thomalla, Goetz - Tomppo, Liisa - Noel, van Horn - Zeller, Julia - Ziemann, Ulf - Zuern, Christine S - Hartig, Florian - Tuennerhoff, Johannes PY - 2024 TI - Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial JF - International Journal of Stroke VL - 19 IS - 1 SP - 120-126 EP - 120-126 PB - SAGE PUBLICATIONS LTD SN - 17474930 KW - Normobaric oxygen therapy KW - NBO KW - hyperoxygenation KW - neuroprotection KW - penumbra KW - ischemic stroke KW - thrombectomy UR - https://journals.sagepub.com/doi/10.1177/17474930231185275 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. ER -
POLI, Sven, Joshua MBROH, Jean-Claude BARON, Aneesh B SINGHAL, Daniel STRBIAN, Carlos MOLINA, Robin LEMMENS, Guillaume TURC, Robert MIKULÍK, Patrik MICHEL, Turgut TATLISUMAK, Heinrich J AUDEBERT, Martin DICHGANS, Roland VELTKAMP, Johannes HUESING, Holm GRAESSNER, Jens FIEHLER, Joan MONTANER, Adedolapo Kamaldeen ADEYEMI, Katharina ALTHAUS, Juan F ARENILLAS, Benjamin BENDER, Frank BENEDIKT, Gabriel BROOCKS, Ina BURGHAUS, Pere CARDONA, Milani DEB-CHATTERJI, Martina CVIKOVÁ, Luc DEFREYNE, De Herdt VEERLE, Olivier DETANTE, Ulrike ERNEMANN, Fabian FLOTTMANN, Lidia Garcia GUILLAMON, Monika GLAUCH, Alexandra GOMEZ-EXPOSITO, Benjamin GORY, Sylvie Sylvie GRAND, Michal HARŠÁNY, Till Karsten HAUSER, Olivier HECK, Dimitri HEMELSOET, Florian HENNERSDORF, Julia HOPPE, Pia KALMBACH, Lars KELLERT, Martin KOHRMANN, Markus KOWARIK, Blanca LARA-RODRIGUEZ, Loic LEGRIS, Tobias LINDIG, Steffen LUNTZ, Jay LUSK, Mac Grory BRIAN, Andreas MANGER, Nicolas MARTINEZ-MAJANDER, Annerose MENGEL, Johannes MEYNE, Susanne MULLER, Sibu MUNDIYANAPURATH, Olivier NAGGARA, Krassen NEDELTCHEV, Thanh N NGUYEN, Maike A NILSSON, Michael OBADIA, Khouloud POLI, Jan C PURRUCKER, Silja RATY, Sebastien RICHARD, Hardy RICHTER, Clotilde SCHILTE, Eckhard SCHLEMM, Linda STOHR, Benjamin STOLTE, Marek SYKORA, Goetz THOMALLA, Liisa TOMPPO, van Horn NOEL, Julia ZELLER, Ulf ZIEMANN, Christine S ZUERN, Florian HARTIG and Johannes TUENNERHOFF. Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial. \textit{International Journal of Stroke}. LONDON: SAGE PUBLICATIONS LTD, 2024, vol.~19, No~1, p.~120-126. ISSN~1747-4930. Available from: https://dx.doi.org/10.1177/17474930231185275.