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Phase 2 N=256 Randomized Triple-blind Treatment

Aggressive Antipyretics for Fever Reduction in CNS Malaria

Malaria · Seizures · Coma · Parasitemia · Hyperpyrexia

Enrolled (actual)
256
Serious AEs
15.6%
Results posted
Mar 2024
Primary outcome: Primary: Mean Maximum Temperature — 38.6; 39.2 degrees of Celsius — p=<0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Acetaminophen (Drug); Ibuprofen (Drug); placebo for acetaminophen (Drug); placebo for ibuprofen (Drug)
Age
Pediatric · 2+ yrs
Sex
All
Sponsor
University of Rochester
Primary completion
Dec 2022

Outcome Measures

OutcomeResultp-value
PRIMARY
Mean Maximum Temperature
38.6; 39.2 <0.0001 sig
PRIMARY
Seizure Severity
107; 88; 10; 6; 10; 34 <0.05 sig
SECONDARY
Parasite Clearance
86.3; 80 <0.05 sig
SECONDARY
Area-under-the-curve (AUC) of Fever ≥ 38.5°C (Best)
67; 37; 47; 54; 14; 37 <0.05 sig

Summary

The study will examine whether prophylactic and scheduled treatment with acetaminophen and ibuprofen can decrease the maximum temperature experienced during the acute illness in children with CNS malaria.

Eligibility Criteria

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03399318). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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