Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria
Information source: Makerere University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cerebral Malaria
Intervention: Intrarectal quinine (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Makerere University Official(s) and/or principal investigator(s): Jane Achan, MBChB, Principal Investigator, Affiliation: Department of Paediatrics and Child Health, Makerere University
Summary
Cerebral malaria is the most lethal complication of P. falciparum infection with a mortality
rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral
malaria. However its administration is often not feasible due to lack of simple equipment or
trained staff. When referral is not possible, a viable alternative is needed. The
intrarectal route is of interest in children since it is painless and simple. Studies of the
efficacy of intrarectal quinine in the treatment of cerebral malaria are limited. The study
aims to establish the efficacy of intrarectal quinine in the treatment of childhood cerebral
malaria.
Clinical Details
Official title: Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria: a Randomized Clinical Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Parasite clearance time
Secondary outcome: Fever clearance timeComa recovery time Time to sit unsupported Time to begin oral intake Mortality Neurological sequelae Adverse drug events
Detailed description:
Cerebral malaria is the most lethal complication of P. falciparum infection with a mortality
rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral
malaria. However its administration is often not feasible due to lack of simple equipment or
trained staff. When referral is not possible, a viable alternative is needed. The
intrarectal route is of interest in children since it is painless and simple. A few studies
in Francophone Africa have reported clinical efficacy and tolerance of intrarectal quinine.
Although the studies were randomized trials, they were not blinded and did not use the WHO
definition of cerebral malaria as selection criteria.
The current study aims to establish whether intrarectal quinine is as effective and as safe
as intravenous quinine in the treatment of childhood cerebral malaria.
To address the shortcomings of the Francophone African studies, the investigators have
designed a randomized, double blind placebo controlled clinical trial to include patients
who meet the WHO definition of cerebral malaria.
Hypothesis:
Intrarectal quinine (15mg/kg every 8 hours) given to children with cerebral malaria, will
lead to a shorter parasite clearance time (39. 9 hours) than intravenous quinine (55. 0
hours).
The investigators calculated a sample size of 54 patients in each group for 90% power and
95% confidence. In the calculation, the researchers assumed that the children receiving
intrarectal quinine would have a mean parasite clearance time of 39. 9 (SD 24. 3) hours and
those receiving intravenous quinine would have a mean parasite clearance time of 55. 0(SD
24. 3) hours (27. 5% effect size), according to a study by Aceng, Byarugaba and Tumwine in
the same hospital.
Eligibility
Minimum age: 6 Months.
Maximum age: 5 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Children aged 6 months to 5 years admitted to Mulago hospital during the study period
who satisfy the World Health Organization (WHO) case definition of cerebral malaria
(Unarousable coma lasting more than 30 minutes after a seizure, with peripheral
asexual P. falciparum parasitaemia and absence of other causes of coma) and whose
caretakers give informed consent.
Exclusion Criteria:
- Patients with diarrhea (more than 4 motions/24 hours)
- Any recent anal pathology (such as rectal bleeding, rectal prolapse)
- Documented quinine treatment in previous 48 hours.
Locations and Contacts
Mulago Hospital, Kampala 7051, Uganda
Additional Information
Related publications: Pussard E, Straczek C, Kaboré I, Bicaba A, Balima-Koussoube T, Bouree P, Barennes H. Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2004 Nov;48(11):4422-6. Barennes H, Sterlingot H, Nagot N, Meda H, Kaboré M, Sanou M, Nacro B, Bourée P, Pussard E. Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria. Eur J Clin Pharmacol. 2003 Feb;58(10):649-52. Epub 2003 Jan 29. Barennes H, Munjakazi J, Verdier F, Clavier F, Pussard E. An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger. Trans R Soc Trop Med Hyg. 1998 Jul-Aug;92(4):437-40. Aceng JR, Byarugaba JS, Tumwine JK. Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial. BMJ. 2005 Feb 12;330(7487):334. Simoes EA, Peterson S, Gamatie Y, Kisanga FS, Mukasa G, Nsungwa-Sabiiti J, Were MW, Weber MW. Management of severely ill children at first-level health facilities in sub-Saharan Africa when referral is difficult. Bull World Health Organ. 2003;81(7):522-31. Epub 2003 Sep 3.
Starting date: September 2003
Last updated: August 3, 2005
|