- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03399318
Aggressive Antipyretics for Fever Reduction in CNS Malaria
Aggressive Antipyretics in CNS Malaria: A Randomized-Controlled Trial Assessing Antipyretic Efficacy and Parasite Clearance Effects
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Evidence of Plasmodium falciparum malaria infection by peripheral blood smear or rapid diagnostic test
- Central nervous system (CNS) symptoms associated with malaria. CEREBRAL MALARIA (CM): Impaired consciousness with a Blantyre Coma Score (BCS)(73) ≤2 in children under 5 years or a Glasgow Coma score (GCS) ≤10 in children ≥5 years OR CNS MALARIA: Complicated seizure(s), meaning prolonged (>15 minutes), focal or multiple; or impaired consciousness or other evidence of impaired consciousness (confusion, delirium) without frank coma (BCS>2, GCS =11-14)
Exclusion Criteria:
- Circulatory failure (cold extremities, capillary refill > 3 seconds, sunken eyes, ↓ skin turgor)
- Vomiting in the past 2 hours
- Serum creatinine (Cr) > 1.2 mg/dL
- A history of liver disease
- Jaundice or a total bilirubin of >3.0mg/dL
- A history of gastric ulcers or gastrointestinal bleeding
- A history of thrombocytopenia or other primary hematologic disorder
- Petechiae or other clinical indications of bleeding abnormalities
- A known allergy to ibuprofen, acetaminophen, aspirin or any non-steroidal medication
- Any contraindication for nasogastric tube (NGT) placement and/or delivery of enteral medications
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Usual Care
will receive placebo for acetaminophen and placebo for ibuprofen.
If they have a temperature over 38.5 degrees Celsius, they will receive acetaminophen (15mg/kg, Q6 hours), as needed.
If the fever persists, a cooling fan will be added.
|
placebo for ibuprofen
Other Names:
placebo for acetaminophen for children in the Usual Care arm For children in the Aggressive Antipyretic Arm, when they have a temperature over 38.5 degrees Celsius they are treated with a placebo
Other Names:
|
Experimental: Aggressive Antipyretics
regardless of temperature, children allocated to this arm will receive acetaminophen (30 milligrams (mg)/ kilogram (kg) load then 15mg/kg Q6 hours) and ibuprofen (10mg/kg Q 6 hours) for 72 hours.
Pediatric syrup formulations of both agents will be administered orally or via nasogastric tube.
For temperatures over 38.5 degrees Celsius, placebo will be added and if the fever persists, a cooling fan will be added.
|
30 mg/kg load then 15mg/kg Q6 hours for the Aggressive Antipyretic Arm Acetaminophen is also given to children in the placebo arm when they have a fever over 38.5 degrees Celsius during scheduled clinical assessments
Other Names:
10 mg/kg Q6 hours for the Aggressive Antipyretic Arm
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Maximum Temperature
Time Frame: 72 hours
|
Mean maximum temperature (Tmax). Tmax will be defined as the highest temperature during the study duration (72 hours) in degrees Celsius recorded by a continuous temperature monitor. The continuous temperature monitors are not magnetic resonance imaging (MRI) compatible. If TMAX is a clinical temperature obtained when continuous monitoring data is not available, the clinical TMAX will be used as the primary outcome. |
72 hours
|
Seizure Severity
Time Frame: 72 hours
|
Seizures were categorized as none, single and brief, or multiple or prolonged, yielding a three-category outcome.
|
72 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Parasite Clearance
Time Frame: 72 hours
|
Parasite clearance was based upon AUC for plasma HRP2 concentration every six hours
|
72 hours
|
Area-under-the-curve (AUC) of Fever ≥ 38.5°C (Best)
Time Frame: 72 hours
|
AUC fever for temperatures above 37.5 degrees Celsius based upon continuous temperature monitoring A secondary efficacy measure included fever exposure as measured by the area under the temperature × time curve for T≥38.5°C during the 72-hour follow-up period, categorized as 0, > 0 and < 2, and ≥ 2 degree-hours.
An ordinal logistic regression model assuming proportional odds with terms for treatment group, country, and disease severity as covariates was used to derive the estimated adjusted treatment group odds ratio and associated 95% confidence interval.
Sensitivity analyses with best-case and worst-case imputation were performed to accommodate missing data for the 12 participants with insufficient temperature data to determine the proper outcome category
|
72 hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gretchen L Birbeck, MD, University of Rochester
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Infections
- Systemic Inflammatory Response Syndrome
- Inflammation
- Neurologic Manifestations
- Wounds and Injuries
- Vector Borne Diseases
- Sepsis
- Parasitic Diseases
- Protozoan Infections
- Body Temperature Changes
- Heat Stress Disorders
- Mosquito-Borne Diseases
- Seizures
- Malaria
- Hyperthermia
- Fever
- Parasitemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antipyretics
- Acetaminophen
- Ibuprofen
Other Study ID Numbers
- RSRB00067717
- R01NS102176 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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