Clinical trial NCT01388842: Evaluation of the Efficacy and Safety of Inhaled Nitric Oxide as Adjunctive Treatment for Cerebral Malaria in Children
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 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria, Cerebral
Keywords: severe malaria
children
adjunctive treatment
Lead sponsor: Epicentre
Sponsor class: OTHER
Collaborators: name: Mbarara University of Science and Technology
name: Massachusetts General Hospital
name: Harvard Medical School (HMS and HSDM)
name: Medecins Sans Frontieres, Netherlands
First posted: 2011-07-07
Enrollment: 92
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Angiopoietin 1 (Ang-1)
timeFrame: 48 hours
Secondary outcomes:
measure: Mortality
timeFrame: 48 hours
measure: coma score
timeFrame: 48 hours
measure: retinopathy
timeFrame: every 6 hours
measure: tone
timeFrame: 48 hours
measure: Measure of occurrence of neurological sequelae in children
timeFrame: months 1, 3 and 6
measure: Vital signs
timeFrame: every 6 hours
measure: oxygen saturation
timeFrame: every 6 hours
Other outcomes:
Locations:
city: Mbarara
country: Uganda
facility: Mbarara Regional Referral Hospital
Study officials:
affiliation: Epicentre
name: Juliet Mwanga-Amumpaire, Dr
role: PRINCIPAL_INVESTIGATOR
References: