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

NCT01388842 | Completed Phase 2 DMC

• 1 other identifier: Epicentre/MBA/2011/NO
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Cerebral

Keywords

severe malaria; children; adjunctive treatment

Outcome Measures

Primary Outcomes (1)

• Angiopoietin 1 (Ang-1)

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

  48 hours

Secondary Outcomes (7)

• Mortality

  48 hours

• coma score

  48 hours

• retinopathy

  every 6 hours

• tone

  48 hours

• Measure of occurrence of neurological sequelae in children

  months 1, 3 and 6

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Controls will receive small pulses of placebo study drug via the INOpulse delivery system. Oxygen saturation will be maintained above 94% by adding oxygen to inspired gas via a loose fitting mask when necessary.

Drug: Placebo

inhaled nitric oxide

EXPERIMENTAL

Subjects randomized to the intervention arm will receive a dose equivalent to 80 ppm iNO in air using an INOpulse delivery system for 24 hours per day for a minimum of two days and until clinical improvement (coma recovery), death or a maximum of 5 days. Oxygen saturation will be maintained above 94% by adding oxygen to inspired gas via a loose fitting mask when necessary.

Drug: inhaled nitric oxide

Interventions

inhaled nitric oxide DRUG

Study drug will be administered using an INOpulse delivery system that delivers small pulses of study drug to the patient via a nasal cannula. Subjects randomized to the intervention arm will receive a dose equivalent to 80 ppm iNO in air for 24 hours per day for a minimum of two days and until clinical improvement (coma recovery), death or a maximum of 5 days.

Also known as: INOmax (nitric oxide) for inhalation

inhaled nitric oxide

Placebo DRUG

The placebo will be administered using an INOpulse delivery system that delivers small pulses of study drug to the patient via a nasal cannula. Subjects randomized to the placebo arm will receive nitrogen in air for 24 hours per day for a minimum of two days and until clinical improvement (coma recovery), death or a maximum of 5 days.

Also known as: Nitrogen in air

Placebo

Eligibility Criteria

• Age: 2 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Epicentre: lead
• Mbarara University of Science and Technology: collaborator
• Massachusetts General Hospital: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Medecins Sans Frontieres, Netherlands: collaborator

Study Sites (1)

Mbarara Regional Referral Hospital

Mbarara, Uganda

Location

MeSH Terms

Conditions

Malaria, Cerebral; Malaria

Interventions

Endothelium-Dependent Relaxing Factors; Nitric Oxide; Nitrogen; Air

Condition Hierarchy (Ancestors)

Central Nervous System Protozoal Infections; Central Nervous System Parasitic Infections; Central Nervous System Infections; Infections; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Elements; Gases; Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Juliet Mwanga-Amumpaire, Dr

  Epicentre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2010
• First Posted: July 7, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: March 2, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)