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 Trial
2 Months
12 Years
Both
Cerebral Malaria
Trial Information
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 Trial
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.
Inclusion Criteria:
- Age between 2 months and 12 years.
- With malaria infection confirmed by a malaria antigen test and/or a positive blood
smear examination
- AND sustained coma: achieving a Blantyre Coma Score less than 3 for 2, or more, hours
after ruling out and treating hypoglycemia (blood glucose less than 2.2 mmol/l),
ruling out meningitis, and ruling out and treating active clinical seizures.
Exclusion Criteria:
- Refusal to participate
- Other cause of coma (toxic or pre-existing severe neurological disease)
- Terminal respiratory failure (due to brainstem coning)
- Coagulopathic
- Clinically unstable enough to preclude venipuncture and phlebotomy
- Severe malnutrition defined by edema or a weight-for-height minus 3 SD;
- Evidence of pre-existing brain injury
- Advanced AIDS defined by WHO clinical staging 4;
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Angiopoietin 1 (Ang-1)
Outcome Description:
Increase in Ang-1 between inclusion and 48 hours of combined therapy (iNO or placebo plus antimalarial chemotherapy)
Outcome Time Frame:
48 hours
Safety Issue:
No
Principal Investigator
Juliet Mwanga, Dr
Investigator Role:
Principal Investigator
Investigator Affiliation:
Epicentre
Authority:
France: Committee for the Protection of Personnes
Study ID:
Epicentre/MBA/2011/NO
NCT ID:
NCT01388842
Start Date:
September 2011
Completion Date:
December 2013
Related Keywords:
- Cerebral Malaria
- severe malaria
- children
- adjunctive treatment
- Malaria
- Malaria, Cerebral
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