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

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT02492178

Collaborator

Kinshasa School of Public Health (Other)

Enrollment

Location

Arms

Duration (Months)

27.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: Intrarectal artesunate Drug: Intravenous artesunate Drug: Intravenous quinine	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Oct 1, 2015

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IR artesunate + IV 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.	Drug: Intrarectal artesunate Other Names: artesunate suppositories Drug: Intravenous artesunate Other Names: parenteral artesunate Drug: Intravenous quinine Other Names: parenteral quinine
Experimental: IV artesunate + IR 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.	Drug: Intrarectal artesunate Other Names: artesunate suppositories Drug: Intravenous artesunate Other Names: parenteral artesunate Drug: Intravenous quinine Other Names: parenteral quinine

Arm

Intervention/Treatment

Experimental: IR artesunate + IV 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.

Drug: Intrarectal artesunate

Other Names:

artesunate suppositories

Drug: Intravenous artesunate

Other Names:

parenteral artesunate

Drug: Intravenous quinine

Other Names:

parenteral quinine

Experimental: IV artesunate + IR 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.

Drug: Intrarectal artesunate

Other Names:

artesunate suppositories

Drug: Intravenous artesunate

Other Names:

parenteral artesunate

Drug: Intravenous quinine

Other Names:

parenteral quinine

Outcome Measures

Primary Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Weight ≥6 kilograms and ≤ 34 kilograms
Severe malaria (WHO Guidelines 2013; Appendix 1)
1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kinshasa School of Public Health	Kinshasa		Congo, The Democratic Republic of the

Sponsors and Collaborators

University of Oxford
Kinshasa School of Public Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Oxford

ClinicalTrials.gov Identifier:

NCT02492178

Other Study ID Numbers:

REACH

First Posted:

Jul 8, 2015

Last Update Posted:

Dec 3, 2015

Last Verified:

Dec 1, 2015

Additional relevant MeSH terms:

Malaria

Artesunate

Quinine

Study Results

No Results Posted as of Dec 3, 2015