Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04037332 |
| Other study ID # |
P 001-18-2.0 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 27, 2018 |
| Est. completion date |
July 31, 2020 |
Study information
| Verified date |
July 2019 |
| Source |
Swiss Tropical & Public Health Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Currently, 16 African countries include the use of pre-referral rectal artesunate (RAS) in
their treatment policies. However, guidelines for RAS use vary widely across countries and
inappropriate use of RAS as a monotherapy and consequential development of resistances
against artemisinin based treatments is of particular concern.
In the frame of the Unitaid-funded "Community Access to Rectal Artesunate for Malaria"
(CARAMAL) Project, quality-assured RAS will be rolled in selected areas of the Democratic
Republic of the Congo (DRC), Nigeria and Uganda. Approximately 3,000 treatments of RAS will
be dispensed by trained community health workers to children <5 years of age in each project
country per year.
Linked to the tracking of (severe) malaria patients in the frame of the CARAMAL project, this
study will assess the frequency of artemisinin resistance markers in the study settings and
tentatively assess whether the introduction of RAS could increase the selection of resistant
P. falciparum strains. The study will be conducted in close collaboration with the Global
Malaria Programme of the WHO. Finger-prick blood samples will be collected from children < 5
years of age with signs of severe febrile illness and a positive mRDT presenting to
community-based providers and referral facilities before and after the pilot roll-out of
pre-referral RAS at community level.
Description:
Currently, 16 African countries include the use of pre-referral rectal artesunate (RAS) in
their treatment policies and a number of countries have begun to implement RAS. However,
guidelines for RAS use vary widely across countries and often do not align with WHO
recommendations. Of particular concern in this context is the inappropriate use of RAS as a
monotherapy (i.e. without subsequent ACT treatment).
In the frame of the Unitaid-funded "Community Access to Rectal Artesunate for Malaria"
(CARAMAL) Project, quality-assured (QA) RAS will be rolled out through integrated Community
Case Management (iCCM) schemes in selected areas of the Democratic Republic of the Congo
(DRC), Nigeria and Uganda. The goal of the CARAMAL Project is to contribute to reducing
malaria mortality in children by improving the community management of suspected severe
malaria cases. The project will contribute to this goal by advancing the development of
operational guidance to catalyse effective and appropriate scale-up of quality-assured rectal
artesunate (RAS) as pre-referral treatment of severe malaria.
In the frame of the CARAMAL project, approximately 3,000 treatments of RAS will be dispensed
by trained community health workers to children <5 years of age in each project country per
year. Children treated with pre-referral RAS will be referred to a higher-level health
facility for comprehensive clinical management, including the administration of a full course
of an artemisinin-based combination therapy, as per WHO guidelines.
While phenotypic resistance of the Plasmodium parasites against artemisinin has not yet been
document in the study settings, this potential threat is a major concern. The administration
of artemisinin monotherapies increases drug pressure, which may lead to the selection of drug
resistance conferring mutations. Mutations in portions of a P. falciparum gene encoding kelch
(K13)-propeller domains are the currently known major determinant of partial resistance
against artemisinin. Data on artemisinin resistance of Plasmodium parasites in the CARAMAL
Project countries are patchy. K13-propeller polymorphisms previously reported from Cambodia
have been found e.g. in parasites from northern Uganda, but the mutations linked to
artemisinin resistance were uncommon and did not seem to increase over time. The general
notion is that numerous K13 polymorphisms circulate in Africa but their distribution does not
currently support the spread of artemisinin resistance.
Linked to the tracking of (severe) malaria patients in the frame of the CARAMAL project, this
study will assess the frequency of artemisinin resistance markers in the study settings and
tentatively assess whether the introduction of RAS could increase the selection of resistant
P. falciparum strains. The study will be conducted in close collaboration with the Global
Malaria Programme of the WHO. Finger-prick blood samples will be collected from children < 5
years of age with signs of severe febrile illness and a positive mRDT presenting to
community-based providers and referral facilities before and after the pilot roll-out of
pre-referral RAS at community level.
Dried blood spots on filter papers will be sent to a WHO-chosen laboratory (Malaria Molecular
Epidemiology Unit at the Pasteur Institute in Cambodia) for molecular analyses to assess the
presence of markers of artemisinin resistance (K13-propeller sequence polymorphisms).
