Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial

Abstract

ContributionsMagdy Selim --organized the trial hypotheses, designed the trial, provided guidance about the data analysis and interpretation and presentation of the data, and drafted most of the sections of the manuscript. Lydia Foster --involved in the statistical analysis and data interpretation, and Contributed to the development and revisions to the manuscript. Claudia Moy --involved in the oversight of the trial conduct and progress Guohua Xi --organized the trial hypotheses, and provided critical revisions to the manuscript. MH, MJ, VS, and WC contributed to recruitment and randomization of trial participants, and provided critical revisions to the manuscript. LM and SG were involved in the design of the trial and provided critical revisions to the manuscript. Casey Norton --provided volumetric measurements of imaging data. Yuko Palesch --involved in the design of the study, statistical analysis and data interpretation, and provided critical revisions to the manuscript. Sharon yeatts --involved in the design of the study, statistical analysis and data interpretation, and contributed to the development and revisions to the manuscript. The idef investigators (see appendix) --contributed to the identification and, when eligible, randomization of trial participants. DECLARATION OF INTERESTSThis was an investigator-initiated study, funded by the NINDS (U01 NS074425). Deferoxamine Mesylate is a generic drug, and there was no commercial or industrial support for the trial. None of the authors has any competing interests related to the submitted work. MS reports grants from the NIH/NINDS (i-DEF) and the American Heart Association (outside the submitted work), and personal fees for serving on the advisory board of CSL Behring (outside the submitted work) during the conduct of the trial. SDY reports grant support from the NINDS, personal fees from Genentech and other fees from CR Bard Inc. (outside the submitted work) during the conduct of the study. SG, LDF, YP, and GX report grants from the NIH/NINDS. MDH reports personal fees from Merck, nonfinancial support from Hoffmann-La Roche Canada Ltd, grants from Covidien (Medtronic), grants from Boehringer-Ingleheim, grants from Stryker Inc., grants from Medtronic LLC, grants from NoNO Inc., (outside the submitted work); In addition, MDH has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients pending to US Patent office Number: 62/086,077 and owns stock in Calgary Scientific Incorporated, a company that focuses on medical imaging software, is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, and NINDS. LM, VS, WC, MJ, CM, and CN have nothing to disclose.

Luteolin Exerts Neuroprotection via Modulation of the p62/Keap1/Nrf2 Pathway in Intracerebral Hemorrhage

“…ICH exhibits high disability and mortality rates. Moreover, ICH has become a heavy burden for global health care systems and societies (Selim et al, 2019). Supportive medical care has represented the main treatment for ICH but has yielded an insufficient efficacy (Hanley et al, 2019).…”

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

“…Deferoxamine has currently reached clinical trials for ICH. The Deferoxamine Mesylate in Patients with Intracerebral Haemorrhage (i‐DEF) phase 2 trial evaluated clinical outcomes after deferoxamine treatment and showed promising results after 180 days (mRS 0‐2 of 45.2% in the deferoxamine group vs 35.6% in the placebo group), although the trial did not meet the primary outcomes at 90 days. Clinical outcome differences in favor of deferoxamine exceeded the prespecified futility threshold at 180 days which was not met at 90 days, showing future need to explore deferoxamine.…”

Challenges in Intracerebral Hemorrhage Clinical Research?

“…The results of the two trials were somewhat contradicting and hence, no clear answer could be derived from them. A phase II trial failed to prove that the iron chelator deferoxamine, used as a neuroprotective agent, improved outcomes in ICH [3]. Tranexamic acid, an antifibrinolytic drug, was investigated in a large randomized placebo-controlled trial [4].…”