Severe Malaria in Remote Areas- Closing the Evidence Gap

NCT ID: NCT06806956

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 2016 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-03-10
• Study Completion Date: 2027-04-30

Brief Summary

The goal of this observational study is to assess whether the giving of rectal artesunate and a three day course of an Artemisinin based Combination Therapy (ACT) to children aged 6 months and ≤ 5 years with severe malaria when referral is not feasible is non inferior to giving of injectable artesunate and three day course of an ACT. The three primary objectives are:

• To evaluate the clinical outcomes of rectal artesunate plus Artemisinin based Combination Therapy for patients 6 months to ≤ 5 years in areas where referral for follow-up treatment with injectable artesunate is not feasible, compared to outcomes obtained after full referral is completed.
• To evaluate feasibility of provision of rapid treatment of severe malaria with rectal artesunate in children 6 months to ≤ 5 years not able to access a referral health facility, by a community health worker or in health facility where there is no injectable artesunate available.
• To evaluate the impact of reinforcing the integrated Community Case Management (iCCM) on access to the formal health care system

The study is being done in Nchelenge district in Zambia and Kapolowe district in the Democratic Republic of Congo. It will enrol 1008 children with severe malaria and an equal number of children with simple malaria

Conditions

Severe Malaria

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Two groups i.e rectal artesunate +ACT group while the other is injectable artesunate +ACT group

The group of interest is children aged between 6 months and less than or equal to 5 years with severe malaria. However, we will also enrol children of the same age group with simple malaria and non malaria severe disease to compare their journeys as well

Treatment of severe malaria with rectal artesunate + Artemisinin based Combination Therapy is not inferior to rectal artesunate + injectable artesunate + ACT in terms of effectiveness in remote areas

Intervention Type: DRUG

The Community Health Worker will give rectal artesunate (RAS) +artemisinin based combination Therapy (ACT) to children aged 6 months to less than or equal to 5 years who fail to make the referral trip. Those who make the referral trip will receive injectable artesunate and artemisinin based Combination Therapy for three days. Giving of RAS +ACT is unique to this study. Children with non malaria severe disease will also receive amoxicillin from the community health worker before they are referred to the next level of care

Interventions

Treatment of severe malaria with rectal artesunate + Artemisinin based Combination Therapy is not inferior to rectal artesunate + injectable artesunate + ACT in terms of effectiveness in remote areas

The Community Health Worker will give rectal artesunate (RAS) +artemisinin based combination Therapy (ACT) to children aged 6 months to less than or equal to 5 years who fail to make the referral trip. Those who make the referral trip will receive injectable artesunate and artemisinin based Combination Therapy for three days. Giving of RAS +ACT is unique to this study. Children with non malaria severe disease will also receive amoxicillin from the community health worker before they are referred to the next level of care

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• From a village without other research interventions
• Children aged from 6 months to ≤5 years that present at the health system and are either; with fever (or history of fever within 2 days) and have a positive mRDT test plus at least one of the following danger signs for malaria (as per standardized national iCCM guidelines):

• convulsions
• inability to drink, eat, or suck
• vomiting all liquids and solids
• altered consciousness/coma
• lethargy
• chest in-drawing Inclusion for uncomplicated malaria
• Children aged from 6 months to ≤5 years; with fever (or history of fever within 2 days) with no danger signs for malaria (as per the standardized national Integrated Management of Childhood Illnesses guidelines) with a positive mRDT for Plasmodium falciparum histidine-rich protein.

Inclusion for severe non-malaria

• From a village without other research interventions
• Children aged from 6 months to ≤5 years that present at the health system and are either; with fever (or history of fever within 2 days) and have a negative mRDT test plus at least one of the following danger signs as per standardized national iCCM guidelines:

• convulsions
• inability to drink, eat, or suck
• vomiting all liquids and solids
• altered consciousness/coma
• lethargy
• chest in-drawing
• For participants in sentinel sites, a written informed consent will be provided by the patient's parent or guardian to take filter paper blood samples and to participate in interviews (questionnaires and IDI) at enrolment, day 14 and day 28 (to assess malaria recurrence and look for markers of resistance). If the parent or guardian is unable to write, thumb print witnessed consent is permitted. The informed consent shall be administered by the CHWs. Willingness and ability of the patient and the parent or guardian to comply with the treatment policy.

Exclusion Criteria

• Use of any investigational or non-registered product or planned use during the study period.
• Participation in other studies within 30 days before the current study begins and/or during study participation.
• Inability to comprehend and/or unwillingness to follow the study protocol.
• For RAS use: if the child has reacted badly to artesunate in the past (in sites where RAS is administered)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universiteit Antwerpen

OTHER

Sponsor Role: collaborator

University of Kinshasa

OTHER

Sponsor Role: collaborator

National Institute for Medical Research, Tanzania

OTHER_GOV

Sponsor Role: collaborator

Medicines for Malaria Venture

OTHER

Sponsor Role: collaborator

Université de Lubumbashi

OTHER

Sponsor Role: collaborator

Tropical Diseases Research Centre, Zambia

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Kinshasa

Kinshasa, Kinshasa City, Democratic Republic of the Congo

Tropical Diseases Research Centre

Ndola, Copperbelt, Zambia

Countries

Democratic Republic of the Congo; Zambia

Other Identifiers

101103191

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Version 2.0 Dated 5 March 2024

Identifier Type: -

Identifier Source: org_study_id