Severe Malaria in Remote Areas- Closing the Evidence Gap

NCT06806956 | Enrolling By Invitation DMC

• 2 other identifiers: Version 2.0 Dated 5 March 2024101103191
• Study Type: observational
• Target: 2,016
• Locations: 2 countries
• Sites: 2

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 28-day PCR corrected cure rate in children aged 6 months to ≤ 5 years treated with RAS+ACT or RAS+injectable artesunate, assessing whether each treatment achieves the clinically acceptable cure rate of 97% ± 5%.
• 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

Keywords

Rectal artesunate; Artemisinin-based Combination Therapy; Injectable artesunate; Community Health Worker; Health Facility

Outcome Measures

Primary Outcomes (3)

• The time from onset of symptoms to initiating treatment

  The time from onset of symptoms to initiating treatment among children 6 months to ≤5 years with severe malaria and/or not able to take oral treatment that seek health care from the CHW or other HF system as primary first contact

  The time from onset of symptoms to initiating treatment

• PCR-corrected cure rate at 28 days from enrollment in patients aged 6 months to ≤5 years.

  PCR-corrected cure rate at 28 Days from enrollment in patients aged 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

  28 Days from enrollment

• Change from baseline proportion of sick children 6 months - ≤5 years at population level that went to the formal health system during the last 6 months including suspected (severe) malaria at month 20 (phase 4).

  Two cross section surveys one at month 1 (baseline) and the other at month 20 (phase 4) will be used to obtain the proportion of sick children 6 months to ≤5 years at population level that were either attended by a Community Health Worker, Health post or Health Centre in the last 6 months

  At month 20 (phase 4)

Study Arms (1)

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

Drug: Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areas

Interventions

Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areas 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

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

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The study population will comprise children 6 months to ≤5 years of age living in Kapolowe, DRC and those living in Nchelenge, Zambia who present with a suspected diagnosis of severe malaria or uncomplicated malaria, confirmed by a rapid diagnostic test; or non-malaria severe disease

You may qualify if:

• 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
• 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.
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tropical Diseases Research Centre, Zambia: lead
• Universiteit Antwerpen: collaborator
• University of Kinshasa: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• Medicines for Malaria Venture: collaborator
• Université de Lubumbashi: collaborator

Study Sites (2)

University of Kinshasa

Kinshasa, Kinshasa City, Democratic Republic of the Congo

Location

Tropical Diseases Research Centre

Ndola, Copperbelt, 10101, Zambia

Location

Biospecimen

Retention: SAMPLES WITH DNA

We are collecting Dried Blood Spots for looking at markers of resistance for malaria

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2024
• First Posted: February 4, 2025
• Study Start: March 10, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); ZA (1)