Treatment of Fever Due to Malaria With Ibuprofen

Fever Clinical Trial

Official title:

Randomised, Double-Blind, Placebo Controlled Study of the Antipyretic Effect of Ibuprofen in Children With Uncomplicated Malaria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00167713
• Other study ID #: 04/2003/IBU
• Status: Completed
• Phase: Phase 4
• First received: September 11, 2005
• Last updated: September 19, 2005
• Start date: April 2003
• Est. completion date: January 2004

Study information

• Verified date: September 2005
• Source: Albert Schweitzer Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gabon: Ministry of Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 7 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fever

Intervention

Drug:
• Ibuprofen

Locations

Country	Name	City	State
Gabon	Medical research Unit, Lambaréné	Lambaréné	Moyen Ogooué

Sponsors (1)

Lead Sponsor	Collaborator
Albert Schweitzer Hospital

Country where clinical trial is conducted

Gabon, 

References & Publications (7)

Brandts CH, Ndjavé M, Graninger W, Kremsner PG. Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. Lancet. 1997 Sep 6;350(9079):704-9. — View Citation

Kluger MJ. Drugs for childhood fever. Lancet. 1992 Jan 4;339(8784):70. — View 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. — View Citation

Kwiatkowski D. Febrile temperatures can synchronize the growth of Plasmodium falciparum in vitro. J Exp Med. 1989 Jan 1;169(1):357-61. — View 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. Epub 2001 Feb 23. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fever clearance time
Primary	Fever time
Primary	Area under the fever curve
Secondary	Parasite clearance time
Secondary	Adverse event during the entire study period

External Links

•   General information on malaria at the website of the Malaria Foundation International
•   Homepage of the Medical Research Unit, Lambaréné