Bio-availability of Rectal Artesunate in Children With Severe Falciparum Malaria (REACH)
Primary Purpose
Malaria
Status
Completed
Phase
Phase 2
Locations
Congo, The Democratic Republic of the
Study Type
Interventional
Intervention
Intrarectal artesunate
Intravenous artesunate
Intravenous quinine
Sponsored by
About this trial
This is an interventional basic science trial for Malaria
Eligibility Criteria
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
Sites / Locations
- Kinshasa School of Public Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IR artesunate + IV artesunate
IV artesunate + IR artesunate
Arm 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.
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Full Information
NCT ID
NCT02492178
First Posted
June 22, 2015
Last Updated
December 2, 2015
Sponsor
University of Oxford
Collaborators
Kinshasa School of Public Health
1. Study Identification
Unique Protocol Identification Number
NCT02492178
Brief Title
Bio-availability of Rectal Artesunate in Children With Severe Falciparum Malaria
Acronym
REACH
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Kinshasa School of Public Health
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IR artesunate + IV artesunate
Arm Type
Experimental
Arm 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.
Arm Title
IV artesunate + IR artesunate
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Intrarectal artesunate
Other Intervention Name(s)
artesunate suppositories
Intervention Type
Drug
Intervention Name(s)
Intravenous artesunate
Other Intervention Name(s)
parenteral artesunate
Intervention Type
Drug
Intervention Name(s)
Intravenous quinine
Other Intervention Name(s)
parenteral quinine
Primary Outcome Measure Information:
Title
Pharmacokinetics profile of rectal artesunate
Description
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).
Time Frame
24 hours
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Kinshasa School of Public Health
City
Kinshasa
Country
Congo, The Democratic Republic of the
12. IPD Sharing Statement
Citations:
PubMed Identifier
33526485
Citation
Fanello C, Hoglund RM, Lee SJ, Kayembe D, Ndjowo P, Kabedi C, Badjanga BB, Niamyim P, Tarning J, Woodrow C, Gomes M, Day NP, White NJ, Onyamboko MA. Pharmacokinetic Study of Rectal Artesunate in Children with Severe Malaria in Africa. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02223-20. doi: 10.1128/AAC.02223-20. Print 2021 Mar 18.
Results Reference
derived
Learn more about this trial
Bio-availability of Rectal Artesunate in Children With Severe Falciparum Malaria
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