Bio-availability of Rectal Artesunate in Children With Severe Falciparum Malaria

Phase 2

Completed

• Conditions: Malaria
• Interventions: Drug: Intrarectal artesunate; Drug: Intravenous artesunate; Drug: Intravenous quinine

• Registration Number: NCT02492178
• Lead Sponsor: University of Oxford

Brief Summary

The study aims at describing the pharmacokinetic properties of rectal artesunate in well characterized severely ill patients using intravenous artesunate as a comparator.

Detailed Description

Individually randomized, open label, 2-arm, cross-over, clinical trial. Patients are allocated to receive rectal artesunate at admission and intravenous artesunate after 12 hours or intravenous artesunate at admission and rectal artesunate after 12 hours. All patients are treated for severe malaria with intravenous quinine. Frequent blood samples are taken at fixed intervals after the administration of the first and the second dose of study drug. The time frame is 24 hours and thereafter patients continue the standard antimalarial therapy.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-06-22
• Study Start: 2015-07
• Study First Submitted QC: 2015-07-03
• Study First Posted: 2015-07-08
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-02
• Last Update Posted: 2015-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Weight ≥6 kilograms and ≤ 34 kilograms
• Severe malaria (WHO Guidelines 2013; Appendix 1)
• P. falciparum infection confirmed by Rapid Diagnostic Test (P. falciparum monoinfection or mixed infection with P. ovale or P. malariae)
• Parents or guardian signed Informed Consent

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Exclusion Criteria

• Acute diarrhoea defined as > 3 liquid stools in the previous 24 hours
• Visible anorectal malformations or a disease of the rectum
• Known hypersensitivity to quinine or artesunate
• A documented history of an effective dose of parenteral antimalarial in the preceding 24 hours or a single dose of rectal artesunate in the previous 12 hours or a dose of an artemisinin based combination therapy in the previous 6 hours
• Co-morbidity which in the judgement of the investigator would interfere with the patient treatment or results of the study or place the subject at undue risk
• Participation in another clinical trial or earlier in the same clinical trial

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
IR artesunate + IV artesunate	Intrarectal artesunate	Patients receive 1 dose of intrarectal artesunate (10 mg/ kg b.w.) on admission and 1 dose of intravenous artesunate (2.4 mg/kg body weight) at 12 hours. All patients receive a loading dose of intravenous quinine (20 mg salt/kg b.w.) on admission followed by 10 mg/kg b.w. at 8 and 16 hrs.
IR artesunate + IV artesunate	Intravenous artesunate	Patients receive 1 dose of intrarectal artesunate (10 mg/ kg b.w.) on admission and 1 dose of intravenous artesunate (2.4 mg/kg body weight) at 12 hours. All patients receive a loading dose of intravenous quinine (20 mg salt/kg b.w.) on admission followed by 10 mg/kg b.w. at 8 and 16 hrs.
IR artesunate + IV artesunate	Intravenous quinine	Patients receive 1 dose of intrarectal artesunate (10 mg/ kg b.w.) on admission and 1 dose of intravenous artesunate (2.4 mg/kg body weight) at 12 hours. All patients receive a loading dose of intravenous quinine (20 mg salt/kg b.w.) on admission followed by 10 mg/kg b.w. at 8 and 16 hrs.
IV artesunate + IR artesunate	Intrarectal artesunate	Patients receive 1 dose of intravenous artesunate (2.4 mg/kg b.w) on admission and 1 dose of intrarectal artesunate (10 mg/ kg b.w.) at 12 hours. All patients receive a loading dose of intravenous quinine (20 mg salt/kg b.w.) on admission followed by 10 mg/kg b.w. at 8 and 16 hrs.
IV artesunate + IR artesunate	Intravenous artesunate	Patients receive 1 dose of intravenous artesunate (2.4 mg/kg b.w) on admission and 1 dose of intrarectal artesunate (10 mg/ kg b.w.) at 12 hours. All patients receive a loading dose of intravenous quinine (20 mg salt/kg b.w.) on admission followed by 10 mg/kg b.w. at 8 and 16 hrs.
IV artesunate + IR artesunate	Intravenous quinine	Patients receive 1 dose of intravenous artesunate (2.4 mg/kg b.w) on admission and 1 dose of intrarectal artesunate (10 mg/ kg b.w.) at 12 hours. All patients receive a loading dose of intravenous quinine (20 mg salt/kg b.w.) on admission followed by 10 mg/kg b.w. at 8 and 16 hrs.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics profile of rectal artesunate	24 hours	The pharmacokinetics profile of rectal artesunate (the study drug), consisting of: area under the concentration-time curve; terminal elimination half-life; elimination clearance; apparent volume of distribution will be measured and compared to the pharmacokinetic profile of intravenous artesunate (the comparator).

Trial Locations

Locations (1)

Kinshasa School of Public Health; 🇨🇩 Kinshasa, Congo, The Democratic Republic of the