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

University of Oxford

Status and phase: Completed; Phase 2

Conditions: Malaria

Treatments: Drug: Intrarectal artesunate; Drug: Intravenous quinine; Drug: Intravenous artesunate

Study type: Interventional

Funder types: Other

Identifiers

NCT02492178

REACH

Details and patient eligibility

About

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

Full 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.

Enrollment: 82 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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82 participants in 2 patient groups

IR artesunate + IV artesunate

Experimental group

Description:

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.

Treatment:

Drug: Intravenous artesunate

Drug: Intravenous quinine

Drug: Intrarectal artesunate

IV artesunate + IR artesunate

Experimental group

Description:

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.

Treatment:

Drug: Intravenous artesunate

Drug: Intravenous quinine

Drug: Intrarectal artesunate