Clinical Trial: Evaluation of the Efficacy and Safety of Inhaled Nitric Oxide as Adjunctive Treatment for Cerebral Malaria in Children

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Evaluation of the Efficacy and Safety of Inhaled Nitric Oxide (iNO) as Adjunctive Treatment for Cerebral Malaria in Children: A Randomized Open Label Phase II Clinical Tri

Brief Summary: The purpose of this study is to assess if adding inhaled Nitric Oxide to other malaria treatments can improve the outcome of cerebral malaria in children aged 2months to 12 years.

Detailed Summary: Despite very effective antimalarial treatment, there is a residual and unacceptable high mortality rate of malaria, especially amongst young children. Recent progress has been made in understanding the role of Nitric Oxide (NO) in severe malaria, indicating that NO supplementation is likely to have a beneficial action in severe malaria possibly through down-regulation of inflammatory cytokines like TNF. Of the various ways to supplement NO, iNO appears to be the safest since it is very well studied in critically ill patients and does not cause systemic vasodilation. The safety of NO inhalation has been clearly demonstrated through its wide use in the treatment of persistent pulmonary hypertension in neonates and pulmonary hypertension in children and adults. Extensive data on its safety has been collected. This study is a phase 2 clinical trial that aims at demonstrating the efficacy of iNO when added to antimalarial treatment to treat cerebral malaria. This study will also provide a better understanding of the pathophysiological mechanisms involved in severe malaria.
Sponsor: Epicentre

Current Primary Outcome: Angiopoietin 1 (Ang-1) [ Time Frame: 48 hours ]

Increase in Ang-1 between inclusion and 48 hours of combined therapy (iNO or placebo plus antimalarial chemotherapy)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mortality [ Time Frame: 48 hours ]
    Reduction in mortality at 48 hours
  • coma score [ Time Frame: 48 hours ]
    normalisation of coma score (Blantyre coma scale)
  • retinopathy [ Time Frame: every 6 hours ]
    Normalisation of malaria retinopathy measured by indirect fundoscopy
  • tone [ Time Frame: 48 hours ]
    Improvement of posture and tone
  • Measure of occurrence of neurological sequelae in children [ Time Frame: months 1, 3 and 6 ]
    Reduction of incidence of neurological sequelae, including motor dysfunction, behavioral disorders, hearing, speech and sight disorders and seizure disorders.
  • Vital signs [ Time Frame: every 6 hours ]
    Improvement of vital signs: Systolic and diastolic blood pressure, pulse rate, temperature
  • oxygen saturation [ Time Frame: every 6 hours ]
    Both Hb Oxygen saturation (SpO2) and total MetHb levels continuously measured by pulse oximetry (Rascal Model 7, Massimo Corp.)


Original Secondary Outcome:

  • Mortality [ Time Frame: 48 hours ]
    Reduction in mortality at 48 hours
  • coma score [ Time Frame: 48 hours ]
    normalisation of coma score (Blantyre coma scale)
  • retinopathy [ Time Frame: every 6 hours ]
    Normalisation of malaria retinopathy measured by indirect fundoscopy
  • tone [ Time Frame: 48 hours ]
    Improvement of posture and tone
  • neurological sequelae [ Time Frame: months 1, 3 and 6 ]
    Reduction of incidence of neurological sequelae, including motor dysfunction, behavioral disorders, hearing, speech and sight disorders and seizure disorders.
  • Vital signs [ Time Frame: every 6 hours ]
    Improvement of vital signs: Systolic and diastolic blood pressure, pulse rate, temperature
  • oxygen saturation [ Time Frame: every 6 hours ]
    Both Hb Oxygen saturation (SpO2) and total MetHb levels continuously measured by pulse oximetry (Rascal Model 7, Massimo Corp.)


Information By: Epicentre

Dates:
Date Received: November 23, 2010
Date Started: September 2011
Date Completion:
Last Updated: February 29, 2016
Last Verified: February 2016