Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria

Cerebral Malaria Clinical Trial

Official title:

Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria: a Randomized Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00124267
• Other study ID #: 2001/HD11/524/RQ
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 26, 2005
• Last updated: August 3, 2005
• Start date: September 2003
• Est. completion date: January 2004

Study information

• Verified date: July 2005
• Source: Makerere University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: National Council for Science and Technology
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 5 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Cerebral Malaria
• Malaria
• Malaria, Cerebral

Intervention

Drug:
• Intrarectal quinine

Locations

Country	Name	City	State
Uganda	Mulago Hospital	Kampala

Sponsors (3)

Lead Sponsor	Collaborator
Makerere University	Ministry of Health, Uganda, Sanofi-Synthelabo

Country where clinical trial is conducted

Uganda, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parasite clearance time
Secondary	Fever clearance time
Secondary	Coma recovery time
Secondary	Time to sit unsupported
Secondary	Time to begin oral intake
Secondary	Mortality
Secondary	Neurological sequelae
Secondary	Adverse drug events