Clinical trial NCT00167713: Treatment of Fever Due to Malaria With Ibuprofen
Official title: Randomised, Double-Blind, Placebo Controlled Study of the Antipyretic Effect of Ibuprofen in Children With Uncomplicated Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fever
Keywords: Malaria
Fever
Ibuprofen
Gabon
Lead sponsor: Albert Schweitzer Hospital
Sponsor class: OTHER
First posted: 2005-09-14
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Drugs to treat fever are widely used in children with fever. But there is a controversy about the benefit of reducing fever in children with malaria. Ibuprofen is often used to treat malarial fever. This study evaluates the capacity of ibuprofen to reduce fever in malaria. The effect of ibuprofen on fever compared to only mechanical measures is investigated in children with malaria.

Detailed description: Fever is the most apparent clinical manifestation of Plasmodium falciparum infection during the acute phase. The role of fever in defence against malaria or in other infectious diseases remains unclear. However, it has been shown that febrile temperatures inhibit the growth of P. falciparum in vitro.

Antipyretic drugs are commonly and widely used to treat malarial fever in endemic areas. There is however a controversy about the benefit of reducing fever in children with malaria. Data from Gabon have revealed that neither paracetamol, nor naproxen or metamizol - antipyretics often used in this area - had an effect on fever clearance time. Worryingly, paracetamol increased parasite-clearance times (i.e. inhibited clearance of parasites) and decreased significantly the production of oxygen radicals and tumour necrosis factor (TNF), mechanisms of the innate immune response, pivotal to combat infections.

Another antipyretic drug often used to treat malarial fever in endemic areas is ibuprofen. However, the rationale of its use and its capacity of reducing fever due to P. falciparum infections has never been proven in this area.

Comparison: The effect of ibuprofen plus mechanical fever "treatment" (continuous fanning, tepid sponging, and cooling blankets) is compared to mechanical treatment alone to treat fever in children with malaria.

Eligibility criteria: Inclusion Criteria:

* Uncomplicated falciparum malaria
* Asexual parasitaemia between 20,000 and 200,000/µL
* Fever with temperature above 38 °C or history of fever during the preceding 24 hours
* Informed consent

Exclusion Criteria:

* Effective anti-malarial treatment for the present attack
* Antipyretic use within 6 hours of presentation
* Contraindications to the use of ibuprofen (history of asthma, dyspeptic symptoms, gastro-intestinal bleeding, or allergy to ibuprofen)
* Mixed plasmodial infection
* Haemoglobin \< 7 g/dL
* Packed-cell volume \< 20%
* White cell count \> 16,000/L
* Platelet count \< 40,000/µL
* Schizontaemia \> 50/µL
* Impaired consciousness
* Convulsions or history of convulsions
* Concomitant diseases masking assessment of response

Primary outcomes:
measure: Fever clearance time
measure: Fever time
measure: Area under the fever curve
Secondary outcomes:
measure: Parasite clearance time
measure: Adverse event during the entire study period
Other outcomes:
Locations:
city: Lambaréné
country: Gabon
facility: Medical research Unit, Lambaréné
state: Moyen Ogooué
Study officials:
affiliation: Albert Schweitzer Hospital
name: Michel A. Missinou, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kwiatkowski D. Febrile temperatures can synchronize the growth of Plasmodium falciparum in vitro. J Exp Med. 1989 Jan 1;169(1):357-61. doi: 10.1084/jem.169.1.357.
citation: Long HY, Lell B, Dietz K, Kremsner PG. Plasmodium falciparum: in vitro growth inhibition by febrile temperatures. Parasitol Res. 2001 Jul;87(7):553-5. doi: 10.1007/s004360100374.
citation: Kluger MJ. Drugs for childhood fever. Lancet. 1992 Jan 4;339(8784):70. No abstract available.
citation: Brandts CH, Ndjave M, Graninger W, Kremsner PG. Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. Lancet. 1997 Sep 6;350(9079):704-9. doi: 10.1016/S0140-6736(97)02255-1.
citation: Lell B, Sovric M, Schmid D, Luckner D, Herbich K, Long HY, Graninger W, Kremsner PG. Effect of antipyretic drugs in children with malaria. Clin Infect Dis. 2001 Mar 1;32(5):838-41. doi: 10.1086/319217. Epub 2001 Feb 23.
citation: Krishna S, Pukrittayakamee S, Supanaranond W, ter Kuile F, Ruprah M, Sura T, White NJ. Fever in uncomplicated Plasmodium falciparum malaria: randomized double-'blind' comparison of ibuprofen and paracetamol treatment. Trans R Soc Trop Med Hyg. 1995 Sep-Oct;89(5):507-9. doi: 10.1016/0035-9203(95)90087-x.
citation: Nwanyanwu OC, Ziba C, Kazembe PN. Paracetamol and ibuprofen for treatment of fever in Malawian children aged less than five years. Trans R Soc Trop Med Hyg. 1999 Jan-Feb;93(1):84. doi: 10.1016/s0035-9203(99)90191-8. No abstract available.
citation: Matsiegui PB, Missinou MA, Necek M, Mavoungou E, Issifou S, Lell B, Kremsner PG. Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial. Malar J. 2008 May 26;7:91. doi: 10.1186/1475-2875-7-91.