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Updated: May 31, 2026

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
Nitric oxide for the adjunctive treatment of severe malaria: hypothesis and rationale
Michael Hawkes1, Robert Opika Opoka, Sophie Namasopo
1Sandra A. Rotman Laboratories, McLaughlin-Rotman Centre for Global Health, Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Abstract:
We hypothesize that supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. The rationale for the hypothesized efficacy of iNO rests on: (1) biological plausibility, based on known actions of NO in modulating endothelial activation; (2) pre-clinical efficacy data from animal models of experimental cerebral malaria; and (3) a human trial of the NO precursor l-arginine, which improved endothelial function in adults with severe malaria. iNO is an attractive new candidate for the adjunctive treatment of severe malaria, given its proven therapeutic efficacy in animal studies, track record of safety in clinical practice and numerous clinical trials, inexpensive manufacturing costs, and ease of administration in settings with limited healthcare infrastructure. We plan to test this hypothesis in a randomized controlled trial (ClinicalTrials.gov Identifier: NCT01255215).
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