Clinical trial NCT06806956: Severe Malaria in Remote Areas- Closing the Evidence Gap
Official title: Severe Malaria Treatment With Rectal Artesunate and Artemisinin-based Combination Therapy in Remote Settings
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Severe Malaria
Keywords: Rectal artesunate
Artemisinin-based Combination Therapy
Injectable artesunate
Community Health Worker
Health Facility
Lead sponsor: Tropical Diseases Research Centre, Zambia
Sponsor class: OTHER_GOV
Collaborators: name: Universiteit Antwerpen
name: University of Kinshasa
name: National Institute for Medical Research, Tanzania
name: Medicines for Malaria Venture
name: Université de Lubumbashi
First posted: 2025-02-04
Enrollment: 2016
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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

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


Eligibility criteria: Inclusion Criteria:

Inclusion criteria for severe 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 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)

Primary outcomes:
measure: The time from onset of symptoms to initiating treatment
timeFrame: The time from onset of symptoms to initiating treatment
measure: PCR-corrected cure rate at 28 days from enrollment in patients aged 6 months to ≤5 years.
timeFrame: 28 Days from enrollment
measure: 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).
timeFrame: At month 20 (phase 4)
Secondary outcomes:
Other outcomes:
Locations:
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: University of Kinshasa
city: Ndola
country: Zambia
facility: Tropical Diseases Research Centre
state: Copperbelt
Study officials:
References: