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

Study Overview
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Brief Summary
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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
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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.

Conditions
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Malaria

Intervention / Treatment
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* Drug: Intrarectal artesunate
* Drug: Intravenous artesunate
* Drug: Intravenous quinine


Participation Criteria
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Eligibility Criteria
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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 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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IR artesunate + IV artesunate<br>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. | Drug: Intrarectal artesunate<br> <br> * Other names: artesunate suppositories;Drug: Intravenous artesunate<br> <br> * Other names: parenteral artesunate;Drug: Intravenous quinine<br> <br> * Other names: parenteral quinine;|
| Experimental: IV artesunate + IR artesunate<br>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. | Drug: Intrarectal artesunate<br> <br> * Other names: artesunate suppositories;Drug: Intravenous artesunate<br> <br> * Other names: parenteral artesunate;Drug: Intravenous quinine<br> <br> * Other names: parenteral quinine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics profile of rectal artesunate | 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). | 24 hours |