Malaria, CerebralPhase 2NCT01388842
Evaluation of the Efficacy and Safety of Inhaled Nitric Oxide as Adjunctive Treatment for Cerebral Malaria in Children
A Phase 2 study testing inhaled nitric oxide in people with Malaria, Cerebral, run by Epicentre at 1 site in Uganda.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 months to 12 years
- Conditions the study is for
- Malaria, Cerebral
- What is being tested?
- inhaled nitric oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteUganda
- Study dates
- Sep 2011to Feb 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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;
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Malaria, Cerebral
- Being tested
- inhaled nitric oxide, Placebo
- Keywords
- severe malaria, children, adjunctive treatment
- Medical subject headings
- Malaria, Cerebral, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled nitric oxideDrug
Also called INOmax (nitric oxide) for inhalation
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.
PlaceboDrug
Also called Nitrogen in air
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: inhaled nitric oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Angiopoietin 1 (Ang-1)
Increase in Ang-1 between inclusion and 48 hours of combined therapy (iNO or placebo plus antimalarial chemotherapy)
Measured: 48 hours
Secondary outcomes (7)
Mortality
Reduction in mortality at 48 hours
Measured: 48 hours
coma score
normalisation of coma score (Blantyre coma scale)
Measured: 48 hours
retinopathy
Normalisation of malaria retinopathy measured by indirect fundoscopy
Measured: every 6 hours
tone
Improvement of posture and tone
Measured: 48 hours
Measure of occurrence of neurological sequelae in children
Reduction of incidence of neurological sequelae, including motor dysfunction, behavioral disorders, hearing, speech and sight disorders and seizure disorders.
Measured: months 1, 3 and 6
Vital signs
Improvement of vital signs: Systolic and diastolic blood pressure, pulse rate, temperature
Measured: every 6 hours
oxygen saturation
Both Hb Oxygen saturation (SpO2) and total MetHb levels continuously measured by pulse oximetry (Rascal Model 7, Massimo Corp.)
Measured: every 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malaria, CerebralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epicentre
- Sponsor type
- University, hospital or other
- Collaborators
- Mbarara University of Science and Technology, Massachusetts General Hospital, Harvard Medical School (HMS and HSDM), Medecins Sans Frontieres, Netherlands
- Responsible party
- Sponsor
- Investigators
- Juliet Mwanga-Amumpaire, Dr, Principal investigator, Epicentre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01388842
- Sponsor's protocol ID
- Epicentre/MBA/2011/NO
- Status last verified
- Feb 2016
- First submitted
- 23 Nov 2010
- Last updated
- 2 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01388842
- Acronym / sponsor ID
- Epicentre/MBA/2011/NO
- Conditions
- Malaria, Cerebral
- Keywords
- severe malaria, children, adjunctive treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- EpicentreUniversity, hospital or other
- Collaborators
- Mbarara University of Science and Technology, Massachusetts General Hospital, Harvard Medical School (HMS and HSDM), Medecins Sans Frontieres, Netherlands
- Study start
- Sep 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 7 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboControls 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. |
| inhaled nitric oxide | Experimental | Drug: inhaled nitric oxideSubjects 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. |
Who may qualify
- Ages
- 2 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inhaled nitric oxideAlso: INOmax (nitric oxide) for inhalationStudy 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. | Drug | inhaled nitric oxide |
| PlaceboAlso: Nitrogen in airThe 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. | Drug | Placebo |
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)
7 secondary outcomes
Mortality
Time frame: 48 hours
coma score
Time frame: 48 hours
retinopathy
Time frame: every 6 hours
tone
Time frame: 48 hours
Measure of occurrence of neurological sequelae in children
Time frame: months 1, 3 and 6
Vital signs
Time frame: every 6 hours
oxygen saturation
Time frame: every 6 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2016.
- Individual participant dataSharing planned: No
Related trials for Malaria, Cerebral
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral
RecruitingObservational study
Risk Assessment of Community Spread of Multiple Endemic Infectious Diseases in a One Health Perspective
Dengue, Chikungunya
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juliet Mwanga-Amumpaire, Dr principal investigator
Epicentre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing inhaled nitric oxide in people with Malaria, Cerebral, run by Epicentre at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Angiopoietin 1 (Ang-1) (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2016.