Malaria, CerebralPhase 3TBSNCT03300648
Treating Brain Swelling in Pediatric Cerebral Malaria
A Phase 3 study testing Mechanical ventilation and Hypertonic saline in people with Malaria, Cerebral, run by Michigan State University at 1 site in Malawi.
Trial summary
This study evaluates the effectiveness of two interventions in Malawian children with cerebral malaria at high risk of death. One-third of the participants will receive treatment as usual, one-third will receive treatment as usual and be placed on a mechanical ventilator, and one-third will receive treatment as usual… Read more about this study
- Who is it for?
- Ages 6 months to 12 years
- Conditions the study is for
- Malaria, Cerebral
- What is being tested?
- Mechanical ventilation and Hypertonic saline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteMalawi
- Study dates
- 8 Jan 2018to 31 Dec 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Peripheral P. falciparum parasitemia of any density
- Blantyre Coma Score ≤2
- No evidence of meningitis on lumbar puncture
- Consciousness not regained after correction of hypoglycemia (if hypoglycemia is present)
- Male or female whose age on the day of screening is between 6 months and 12 years old
- Severely increased brain volume on magnetic resonance imaging
- Provision of consent by guardian
- Willingness to return for 1, 6, and 12 month post-randomization follow-up visits
Who cannot join
- Gross malnutrition as evidenced by peripheral edema, hair color changes, or severe wasting
- Advanced Human Immunodeficiency Virus (HIV) disease - defined as known HIV positive status and evidence of severe wasting
- Evidence of recent head trauma by history or physical examination
- Pneumonia as evidenced by oxygen saturation on room air of <85%
- Gastroenteritis and shock as evidenced by capillary refill >3 seconds or skin tenting
Trial locations and contacts
1 site in 1 country.
About this study
This study evaluates the effectiveness of two interventions in Malawian children with cerebral malaria at high risk of death. One-third of the participants will receive treatment as usual, one-third will receive treatment as usual and be placed on a mechanical ventilator, and one-third will receive treatment as usual plus intravenous hypertonic saline.
Read the detailed description
An important mechanism of death in children with cerebral malaria is diffuse cerebral swelling, cerebral herniation, compression of the brainstem respiratory center, and respiratory arrest. In those who survive their illness without specific interventions, reversal of diffuse cerebral swelling is rapid.
Mechanical ventilation may help to preserve life while diffuse brain swelling diminishes. Intravenous hypertonic saline may work as an osmotic diuretic, directly decreasing brain swelling.
- Conditions
- Malaria, Cerebral
- Being tested
- Mechanical ventilation, Hypertonic saline
- Keywords
- coma, pediatrics
- Medical subject headings
- Malaria, Cerebral, Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mechanical ventilationOther
Intubation and mechanical ventilation for a maximum of 7 days
Hypertonic salineDrug
Intravenous 3 percent hypertonic saline for a maximum of 7 days
| Study group | Role | What they receive |
|---|---|---|
| Usual care | No intervention | Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees |
| Mechanical ventilation | Experimental | Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intubation and mechanical ventilation for a maximum of 7 days Receives: Other: Mechanical ventilation |
| Hypertonic saline | Experimental | Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intravenous 3% hypertonic saline for a maximum of 7 days Receives: Drug: Hypertonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Died
Alive or dead
Measured: Within 7 days of randomization
Secondary outcomes (1)
Neurodevelopmental Disability
Presence and severity of neurodevelopmental disability in survivors
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2017
- Study start8 Jan 2018
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned to one of three study arms.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michigan State University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's National Research Institute, Nationwide Children's Hospital, National Institute of Allergy and Infectious Diseases (NIAID), University of Maryland, Baltimore, Kamuzu University of Health Sciences
- Responsible party
- Principal investigator, Terrie Taylor, Michigan State University
- Investigators
- Terrie E Taylor, DO, Principal investigator, Michigan State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03300648
- Sponsor's protocol ID
- TBS
- Other IDs
- U01AI126610
- Acronym
- TBS
- Status last verified
- Feb 2025
- First submitted
- 28 Sep 2017
- Last updated
- 17 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data may be made available to other researchers
Publications
Postels DG. Leveling the Playing Field: Combining Pediatric Neurology and Global Health. Pediatr Neurol. 2021 Jul;120:61-62. doi: 10.1016/j.pediatrneurol.2021.04.012. Epub 2021 Apr 25. No abstract available.
PubMed 34020114
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating Brain Swelling in Pediatric Cerebral Malaria
- ClinicalTrials.gov ID
- NCT03300648
- Acronym / sponsor ID
- TBS / TBS
- Conditions
- Malaria, Cerebral
- Keywords
- coma, pediatrics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Michigan State UniversityUniversity, hospital or other
- Collaborators
- Children's National Research Institute, Nationwide Children's Hospital, National Institute of Allergy and Infectious Diseases (NIAID), University of Maryland, Baltimore, Kamuzu University of Health Sciences
- Study start
- 8 Jan 2018 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 3 Oct 2017 (actual)
- Results
- Posted 17 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effectiveness of two interventions in Malawian children with cerebral malaria at high risk of death. One-third of the participants will receive treatment as usual, one-third will receive treatment as usual and be placed on a mechanical ventilator, and one-third will receive treatment as usual plus intravenous hypertonic saline.
Detailed description
An important mechanism of death in children with cerebral malaria is diffuse cerebral swelling, cerebral herniation, compression of the brainstem respiratory center, and respiratory arrest. In those who survive their illness without specific interventions, reversal of diffuse cerebral swelling is rapid.
Mechanical ventilation may help to preserve life while diffuse brain swelling diminishes. Intravenous hypertonic saline may work as an osmotic diuretic, directly decreasing brain swelling.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- Participants will be randomly assigned to one of three study arms.
| Arm | Type | Receives |
|---|---|---|
| Usual care | No intervention | –Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees |
| Mechanical ventilation | Experimental | Other: Mechanical ventilationHospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intubation and mechanical ventilation for a maximum of 7 days |
| Hypertonic saline | Experimental | Drug: Hypertonic salineHospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intravenous 3% hypertonic saline for a maximum of 7 days |
Who may qualify
- Ages
- 6 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Peripheral P. falciparum parasitemia of any density
- Blantyre Coma Score ≤2
- No evidence of meningitis on lumbar puncture
- Consciousness not regained after correction of hypoglycemia (if hypoglycemia is present)
- Male or female whose age on the day of screening is between 6 months and 12 years old
Key exclusion criteria (5 listed)
- Gross malnutrition as evidenced by peripheral edema, hair color changes, or severe wasting
- Advanced Human Immunodeficiency Virus (HIV) disease - defined as known HIV positive status and evidence of severe wasting
- Evidence of recent head trauma by history or physical examination
- Pneumonia as evidenced by oxygen saturation on room air of <85%
- Gastroenteritis and shock as evidenced by capillary refill >3 seconds or skin tenting
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 |
|---|---|---|
| Mechanical ventilationIntubation and mechanical ventilation for a maximum of 7 days | Other | Mechanical ventilation |
| Hypertonic salineIntravenous 3 percent hypertonic saline for a maximum of 7 days | Drug | Hypertonic saline |
Primary outcome
Number of Participants Who Died
Time frame: Within 7 days of randomization
Alive or dead
1 secondary outcome
Neurodevelopmental Disability
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34020114Postels DG. Leveling the Playing Field: Combining Pediatric Neurology and Global Health. Pediatr Neurol. 2021 Jul;120:61-62. doi: 10.1016/j.pediatrneurol.2021.04.012. Epub 2021 Apr 25. No abstract available.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data may be made available to other researchers
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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.
Terrie E Taylor, DO principal investigator
Michigan State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mechanical ventilation and Hypertonic saline in people with Malaria, Cerebral, run by Michigan State University at 1 site in Malawi.
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 8 inclusion and 5 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 17 Mar 2025. 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 Malawi. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Who Died (time frame: Within 7 days of randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03300648, which also lists 1 linked publication.
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 17 Mar 2025.