Official Title: “The Effect of Paracetamol in the Treatment of Non-Severe Malaria in Children in Guinea-Bissau”

The National Malaria Programme in Guinea-Bissau recommends paracetamol for all children treated for malaria. We, the investigators of the Bandim Health Project, want to evaluate whether this treatment has any effect on: - the well-being of the child; - the parasite clearance time; and - the rate of a re-appearance of parasites during 35 days of follow-up.

Children presenting at Bandim Health Centre with malaria will be treated with chloroquine plus paracetamol or chloroquine plus placebo. Blood samples will be obtained daily for the first 4 days and then once a week until day 35.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2006

A Cochrane Review was unable to show a superior antipyretic effect of paracetamol compared with placebo in febrile children. Recent research suggests that the time to parasite clearance in non-severe malaria is longer in children being given paracetamol. As the costs associated with the use of paracetamol is not trivial and the risk of adverse effects is not negligible, we want to evaluate the effects of paracetamol on: - the well-being of the child; - the parasite clearance time; and - the recrudescence rate.

Children presenting at Bandim Health Centre with symptoms of malaria and a malaria film showing mono-infection with P.falciparum will, following consent to participate, randomly be allocated to treatment with chloroquine and paracetamol or with chloroquine and placebo.

Blood samples will be obtained daily for the first 4 days. The children will be visited and a malaria film taken on day 7 and then weekly until day 35. On inclusion and whenever parasitaemia is detected a capillary blood sample will be taken for PCR analyses to be able to distinguish re-infection from recrudescence.

During follow-up children are recommended to present at the health centre in case of persistent fever or any other symptoms. Examination and treatment will be free of charge.

Whenever a child has re-infection sulfadoxine/pyrimethamine will be used for re-treatment following the recommendation of the National malaria Programme.

After the inclusion of 80 children a preliminary analysis will be performed. If 50% or more of the children in any of the study arms have reappearing parasitaemia the study will be terminated.

If the parasite clearance time and especially the recrudescence rate is higher for children being given paracetamol the current recommendation from the National Malaria Programme should be reconsidered. If children treated with paracetamol feel better during the acute illness making it more likely for them to have en adequate intake of food and liquid this benefit should be considered in the evaluation of the current recommendations.

Intervention(s) in this Clinical Trial

• Drug: acetaminophen (paracetamol)
  • Paracetamol tablets, 50 mg/kg/day for 3 days.
• Other: Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1 Paracetamol
  • Paracetamol as per protocol
• Placebo Comparator: 2 Placebo
  • Inactive placebo as per protocol.

Primary Measures

• parasite clearance time
  • Time Frame: 35 days
    Safety Issue?: No
• recrudescence rate
  • Time Frame: 35 days
    Safety Issue?: No

Secondary Measures

• well-being of the child
  • Time Frame: 35 days
    Safety Issue?: No

Inclusion Criteria:

• < 15 years of age
• Presenting at Bandim Health Centre
• Symptoms suggestive of malaria
• At least 20 P. falciparum parasites per 200 leukocytes
• Live in Bandim (to enable follow-up)

Exclusion Criteria:

• Severely ill children considered to need the services of a hospital by the doctor in charge
• Previous idiosyncratic reactions to chloroquine or paracetamol

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 15 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Bandim Health Project

Overall Clinical Trial Officials and Contacts

Peter Aaby, Professor Study Director Bandim Health Project  

Information obtained from ClinicalTrials.gov on August 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00137566

Study ID Number: PSB-2004-paracetamol

ClinicalTrials.gov Identifier: NCT00137566

Health Authority: Guinea-Bissau: Ministry of Health