Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04767217 |
| Other study ID # |
IRB00014153 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
June 14, 2021 |
| Est. completion date |
January 31, 2024 |
Study information
| Verified date |
January 2024 |
| Source |
Jhpiego |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
WHO recommends that Therapeutic Efficacy Studies (TES) for 1st and 2nd line antimalarial
medicines should be routinely carried out and data made available for decision-making due to
the threat of emergence and spread of artemisinin resistance in malaria-endemic countries,
especially in Africa. In line with this WHO recommendation, Rwanda Ministry of Health (MOH)
is conducting the TES to determine the efficacy of artemether-lumefantrine (ALN), which has
been used in Rwanda for the last 14 years) and dihydroartemisinin-piperaquine (DHA-PPQ),
another WHO-approved drug for the treatment of uncomplicated malaria which, though, has not
been used in Rwanda, is being considered for adoption as a second line or alternative first
line treatment. The objective of this study is to inform the decisions or actions made by a
public health authority (Rwanda Rwanda Ministry of Health) to inform decision on revision of
the antimalarial guidelines and policy in Rwanda. Jhpiego's Impact Malaria project in Rwanda,
with funding and technical oversight from US President's Malaria Initiative (PMI) through
USAID and CDC, will support the Rwanda MOH in its effort to evaluate the efficacy of ALN and
DHA-PPQ in the treatment of children with uncomplicated malaria. The study is being conducted
by Rwanda MOH, with technical support and funding by PMI-USAID through Jhpiego in Rwanda.
Description:
WHO recommends that Therapeutic Efficacy Studies (TES) for 1st and 2nd line antimalarial
medicines should be routinely carried out and data made available for decision-making due to
the threat of emergence and spread of artemisinin resistance in malaria-endemic countries,
especially in Africa. The Rwandan Ministry of Health (MOH) in 2006 adopted WHO-approved
artemether-lumefantrine (ALN) as the first-line drug for the treatment of uncomplicated
Plasmodium falciparum malaria. A clinical trial carried out in 2004-2005 in Rwanda showed
that ALN was very efficacious in children although efficacy varied in different parts of the
country. ALN efficacy was shown to remain high in TES conducted in 2012-2015 and in 2018.
However, both studies found a molecular marker of parasite resistance to artemisinin
(included delayed parasite clearance associated with artemisinin resistance in one site in
2018) and both studies also found high prevalence of markers associated with tolerance to
lumefantrine. The clinical efficacy of ALN therefore needs to be regularly monitored in
Rwanda to ensure this first line treatment is still efficacious. Given the detection of
antimalarial resistance markers in recent TES, it is also important for Rwanda MOH to
determine the efficacy an additional ACT that could be considered for adoption as a second
line or alternative first line treatment. This study will monitor the efficacy of ALN (which
has been used in Rwanda for the last 14 years) and dihydroartemisinin-piperaquine (DHA-PPQ),
another WHO-approved ACT for the treatment of uncomplicated malaria which has not been used
in Rwanda.
In line with the WHO recommendation, Jhpiego Impact Malaria project in Rwanda, with funding
and technical oversight from US President's Malaria Initiative (PMI) through USAID and CDC,
will be supporting the Rwanda MOH Malaria and Other Parasitic Diseases Unit (MOPDD) of the
Rwanda Biomedical Center (RBC) to conduct a TES to monitor the efficacy of ALN and DHA-PPQ in
children with uncomplicated clinical malaria in rural Rwanda. The study is being conducted by
Rwanda MOH MOPDD, with technical support and funding by PMI-USAID through the Jhpiego Impact
Malaria project in Rwanda.
Objective: To evaluate the efficacy of artemether-lumefantrine (ALN) and
dihydroartemisinin-piperaquine (DHA-PPQ) in children with uncomplicated clinical malaria in
rural Rwanda
Study Sites: The study will be conducted in three sentinel sites - Rukara, Bugarama and
Masaka rural health centers- where antimalaria efficacy studies are always carried out in
Rwanda because of the intensity of malaria transmission. Different levels of artemisinin
resistance have been identified in two of these three (Rukara and Bugarama) in previous
studies. At each site, there will be two arms: one for ALN and one for DHA-PPQ.
Study Design: The study will be a two-arm, open-label trial in which patients (children aged
6 months to 59 months) with uncomplicated P. falciparum malaria will be treated with
supervised doses of ALN or DHA-PPQ. Children will be followed for 28 days after treatment for
ALN and 42 days after DHA-PPQ. Data on molecular markers of artemisinin resistance will be
collected at all sites. The study will be conducted at three sites in Rwanda with
historically different efficacy profiles to antimalarials, including ACTs.
The primary endpoint is the clinical and parasitological cure by day 28 (ALN) and day 42
(DHA-PPQ) post-treatment.
Study Period: March 2021 to October 2022
Sample Size: At each site, 88 patients per treatment arm (allowing for 20% loss to follow-up)
would be enrolled. In total, we will enrol 528 patients in our study.
Treatment(s) and follow-up: All children enrolled in the study will be admitted to a health
centre for three days to ensure adherence to treatment regimen, and detect possible adverse
events. Clinical and parasitological parameters will be monitored over a 28-day follow-up
period to evaluate ALN efficacy, and over a 42-day follow-up period to evaluate DHA-PPQ
efficacy.
Exploratory endpoints: to characterize molecular markers of artemisinin and partner drug
resistance in all three sites and the clinical (parasite clearance) and in vitro phenotypes
of resistance in two of the three study sites: Rukara and Masaka.
