Aggressive Antipyretics for Fever Reduction in CNS Malaria
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ClinicalTrials.gov Identifier: NCT03399318 |
Recruitment Status :
Recruiting
First Posted : January 16, 2018
Last Update Posted : October 27, 2020
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Condition or disease | Intervention/treatment | Phase |
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Malaria Seizures Coma Parasitemia Hyperpyrexia | Drug: Acetaminophen Drug: Ibuprofen Drug: placebo for acetaminophen Drug: placebo for ibuprofen | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 284 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Aggressive Antipyretics in CNS Malaria: A Randomized-Controlled Trial Assessing Antipyretic Efficacy and Parasite Clearance Effects |
Actual Study Start Date : | July 2, 2018 |
Estimated Primary Completion Date : | March 31, 2022 |
Estimated Study Completion Date : | June 30, 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: Aggressive Antipyretics
regardless of temperature, children allocated to this arm will receive acetaminophen (30mg/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.
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Drug: Acetaminophen
30 mg/kg load then 15mg/kg
Other Name: Paracetamol Drug: Ibuprofen 10 mg/kg
Other Name: Brufen |
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.
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Drug: placebo for acetaminophen
placebo for acetaminophen
Other Name: Placebo Drug: placebo for ibuprofen placebo for ibuprofen
Other Name: Placebo |
- 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 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.
- Seizures [ Time Frame: 72 hours ]Seizures detected clinically or on daily EEG
- Parasite burden [ Time Frame: 72 hours ]based upon HRP2 levels and quantitative blood film Q6 hourly until aparasitemic on thick blood smear
- Area-under-the-curve of fever [ Time Frame: 72 hours ]AUC fever for temperatures above 37.5 degrees Celsius based upon continuous temperature monitoring

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Ages Eligible for Study: | 2 Years to 11 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test
- CNS symptoms associated with malaria. CEREBRAL MALARIA: 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 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 medica-tion
- Any contraindication for nasogastric tube (NGT) placement and/or delivery of enteral medications

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03399318
Contact: Phillip Thesing, DO | +260962121455 | Phillip_Thesing@urmc.rochester.edu | |
Contact: Karl B Seydel, MD PhD | +265999452989 | seydel@msu.edu |
Malawi | |
Pediatric Research Ward at Queen Elizabeth Central Hospital | Recruiting |
Blantyre, Malawi | |
Contact: Karl B Seydel, MD PhD +265999452989 seydel@msu.edu | |
Contact: Gretchen L Birbeck, MD +265995008069 gretchen_birbeck@urmc.rochester.edu | |
Zambia | |
Chipata Central Hospital | Recruiting |
Chipata, Eastern, Zambia | |
Contact: Suzanna Mwanza, MMED (Peds) +260 (977) 674471 mwanzasue@yahoo.co.uk | |
Contact: Mbinga Mbinga +260 (977) 480413 dr.mbinga@gmail.com | |
University Teaching Hospital's Lusaka Childrens Hospital | Active, not recruiting |
Lusaka, Zambia |
Principal Investigator: | Gretchen L Birbeck, MD | University of Rochester |
Documents provided by Gretchen Birbeck, University of Rochester:
Responsible Party: | Gretchen Birbeck, Professor, University of Rochester |
ClinicalTrials.gov Identifier: | NCT03399318 |
Other Study ID Numbers: |
RSRB00067717 R01NS102176 ( U.S. NIH Grant/Contract ) |
First Posted: | January 16, 2018 Key Record Dates |
Last Update Posted: | October 27, 2020 |
Last Verified: | October 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
HRP2 |
Malaria Parasitemia Seizures Protozoan Infections Parasitic Diseases Neurologic Manifestations Nervous System Diseases Sepsis Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Acetaminophen Ibuprofen |
Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Antipyretics Anti-Inflammatory Agents, Non-Steroidal Anti-Inflammatory Agents Antirheumatic Agents Cyclooxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |