Severe Malaria in Remote Areas- Closing the Evidence Gap (SEMA ReACT)

Tropical Diseases Research Centre, Zambia

Status: Invitation-only

Conditions: Severe Malaria

Treatments: 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

Study type: Observational

Funder types: Other

Identifiers

NCT06806956

101103191 (Other Grant/Funding Number)

Version 2.0 Dated 5 March 2024

Details and patient eligibility

About

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

Enrollment: 2,016 estimated patients

Sex: All

Ages: 6 months to 5 years old

Volunteers: No Healthy Volunteers

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)

Trial design

2,016 participants in 1 patient group

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

Description:

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:

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