Trial reportPloS one2018
Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized double-blind placebo controlled trial.
Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01255215 (Inhaled Nitric Oxide for the Adjunctive Therapy of Severe Malaria), which is not on this map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Inhaled Nitric Oxide for the Adjunctive Therapy of Severe Malaria: a Randomized Controlled Trial
Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Neurodevelopmental Outcomes After Nitric Oxide During Cardiopulmonary Bypass for Open Heart Surgery: A Randomized Clinical Trial.JAMA network open · 2025Trial
- Nitric Oxide Therapeutics: New Hopes for More Effective Tuberculosis Treatment Combine with Targeted and Controlled Nanotechnology.International journal of nanomedicine · 2025Review
- Severe Malaria in Angola: The Clinical Profile and Disease Outcome Among Adults from a Low-Endemic Area.Biomedicines · 2024Article
- Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- The kidney-brain pathogenic axis in severe falciparum malaria.Trends in parasitology · 2023Review
- Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.Frontiers in human neuroscience · 2023Article
- Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Nitric oxide in parasitic infections: a friend or foe?Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Review
- Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.International journal of molecular sciences · 2022Review
- Nitric oxide: Clinical applications in critically ill patients.Nitric oxide : biology and chemistry · 2022Review
- Pediatric Cerebral Malaria.Current tropical medicine reports · 2021Article
- Clinical trials to assess adjuvant therapeutics for severe malaria.Malaria journal · 2020Article
- Safety and Efficacy of Adjunctive Therapy With Artesunate in the Treatment of Severe Malaria: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Review
- New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria.Virulence · 2019Review
- Evaluating Immunopathogenic Biomarkers During Severe Malaria Illness as Modifiers of the Neuropsychologic Benefits of Computer Cognitive Games Rehabilitation in Ugandan Children.The Pediatric infectious disease journal · 2019Article
- Article
- Opportunities for Host-targeted Therapies for Malaria.Trends in parasitology · 2018Review
- Chitinase-3-like 1 is a biomarker of acute kidney injury and mortality in paediatric severe malaria.Malaria journal · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundSevere malaria is a leading cause of acquired neurodisability in Africa and is associated with reduced nitric oxide (NO) bioavailability. A neuroprotective role for inhaled NO has been reported in animal studies, and administration of inhaled NO in preterm neonates with respiratory distress syndrome is associated with a 47% reduced risk of cognitive impairment at two years of age.
methodsA randomized double-blind placebo-controlled trial of inhaled NO versus placebo as an adjunctive therapy for severe malaria was conducted in Uganda between 2011 and 2013. Children received study gas for a maximum 72 hours (inhaled NO, 80 parts per million; room air placebo). Neurocognitive testing was performed on children<5 years at 6 month follow-up. The neurocognitive outcomes assessed were overall cognition (a composite of fine motor, visual reception, receptive language, and expressive language), attention, associative memory, and the global executive composite. Main outcomes were attention, associative memory, and overall cognitive ability.
resultsSixty-one children receiving iNO and 59 children receiving placebo were evaluated. Forty-two children (35.0%) were impaired in at least one neurocognitive domain. By intention-to-treat analysis, there were no differences in unadjusted or unadjusted age-adjusted z-scores for overall cognition (β (95% CI): 0.26 (-0.19, 0.72), p = 0.260), attention (0.18 (-0.14, 0.51), p = 0.267), or memory (0.14 (-0.02, 0.30), p = 0.094) between groups by linear regression. Children receiving inhaled NO had a 64% reduced relative risk of fine motor impairment than children receiving placebo (relative risk, 95% CI: 0.36, 0.14-0.96) by log binomial regression following adjustment for anticonvulsant use.
conclusionsSevere malaria is associated with high rates of neurocognitive impairment. Treatment with inhaled NO was associated with reduced risk of fine motor impairment. These results need to be prospectively validated in a larger study powered to assess cognitive outcomes in order to evaluate whether strategies to increase bioavailable NO are neuroprotective in children with severe malaria.
trial registrationClinicalTrials.gov Identifier: NCT01255215.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.