TY - JOUR
T1 - Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children
T2 - A Phase II Randomized Open-Label Clinical Trial
AU - Mwanga-Amumpaire, Juliet
AU - Carroll, Ryan W.
AU - Baudin, Elisabeth
AU - Kemigisha, Elisabeth
AU - Nampijja, Dorah
AU - Mworozi, Kenneth
AU - Santorino, Data
AU - Nyehangane, Dan
AU - Nathan, Daniel I.
AU - De Beaudrap, Pierre
AU - Etard, Jean François
AU - Feelisch, Martin
AU - Fernandez, Bernadette O.
AU - Berssenbrugge, Annie
AU - Bangsberg, David
AU - Bloch, Kenneth D.
AU - Boum, Yap I.
AU - Zapol, Warren M.
N1 - Funding Information:
Financial support. This work was supported by financial contributions from the International Innovation Fund of Médecins Sans Frontières (MSF) and MSF France; the Anesthesia Center for Critical Care Research and the Department of Anesthesia, Critical Care, and Pain Medicine of Massachusetts General Hospital (Boston, MA); and the Mark and Lisa Schwartz Foundation. This study would not have been possible without generous gas and equipment support from Ikaria and Masimo, and funding for the NO metabolite assays from the University of Southampton School of Medicine, UK.
Funding Information:
This work was supported by financial contributions from the International Innovation Fund of Médecins Sans Frontières (MSF) and MSF France; the Anesthesia Center for Critical Care Research and the Department of Anesthesia, Critical Care, and Pain Medicine of Massachusetts General Hospital (Boston, MA); and the Mark and Lisa Schwartz Foundation. This study would not have been possible without generous gas and equipment support from Ikaria and Masimo, and funding for the NO metabolite assays from the University of Southampton School of Medicine, UK.
Publisher Copyright:
© 2022 The Author.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels-blood methemoglobin and plasma nitrate-increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
AB - Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels-blood methemoglobin and plasma nitrate-increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
KW - Plasmodium falciparum
KW - cerebral malaria
KW - methemoglobin
KW - nitric oxide
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U2 - 10.1093/OFID/OFV111
DO - 10.1093/OFID/OFV111
M3 - Article
AN - SCOPUS:84962907832
SN - 2328-8957
VL - 2
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 3
M1 - OFV111
ER -