Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06337253 |
| Other study ID # |
MOZ202401 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 26, 2024 |
| Est. completion date |
November 26, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Malaria Consortium |
| Contact |
Kevin Baker |
| Phone |
07811266539 |
| Email |
k.baker[@]malariaconsortium.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Seasonal malaria chemoprevention (SMC) is a highly effective community-based intervention to
prevent malaria infections caused by Plasmodium falciparum in areas where the burden of
malaria is high and malaria transmission is seasonal. SMC is commonly seen as a success story
in the Sahel region, however, there are regions in east and southern Africa where malaria
transmission is seasonal, and the burden is high. However, the same decision-making
frameworks that was used in the Sahel are unlikely to be applicable to east and southern
Africa due to higher pre-existing resistance to the drugs used, seasonality heterogeneity,
contextual difference, and unknown cost-effectiveness, amongst others. This study aims to
estimate the chemoprevention efficacy, potential upscale impact, acceptability, and
feasibility of SMC with sulfadoxine-pyrimenthamine + amodiaquine (SP+AQ) medicines in Niassa
Province in Mozambique.
The study is divided into two separate components with different objectives which outputs
feed into each other: a non-randomized controlled trial to estimate the chemoprevention
efficacy of SP+AQ; and a qualitative study that will evaluate the feasibility and
acceptability of the intervention.
These will be the first studies analysing the chemoprevention efficacy, feasibility,
acceptability, and potential scale-up impact of SMC in Niassa Province, Mozambique The
outcomes of these studies aim to guide future policy changes at local, national, and
international levels and potentially allow for a historically successful program to expand in
a sustained and cost-effective way beyond the Sahel region.
Description:
Chemoprevention efficacy component
Outcomes. Primary outcomes of the CPES component are chemoprevention failure (a positive qPCR
for P. falciparum parasites on day 28 after SP+AQ administration or P. falciparum positive
slides at any time from day 7), prevalence of antimalarial resistance markers among
chemoprevention failures and drug concentrations among chemoprevention failures. Secondary
outcomes include uncomplicated malaria within the first 28 days since SP+AQ administration,
participant's hospitalization within the first 28 days, severe malaria within the first 28
days , and severe anaemia levels comparisons at baseline and endline of our study period.
Sample size. Seasonal malaria chemoprevention must be well tolerated and highly effective to
justify its deployment. It is therefore necessary to characterize failure (malaria
breakthrough) rates accurately. A sample size of 500 children per study arm receiving SP+AQ
will have 80% power to detect at least a 3% breakthrough infection rate by day 28 with a 95%
confidence interval of ±1.5%, in settings where infection incidence is at least 6 infections
or more per child per year and chemoprevention efficacy equals that in SMC trials in West
Africa.
Recruitment and data collection. Participant selection will be carried on day 0 of the SMC
implementation campaign by one trained inquirer and one phlebotomist (fieldworkers) that will
follow the SMC community distributors. In each eligible household from both intervention and
control arms one SMC eligible child will be selected to take part in the study . If the
household has more than one SMC eligible child, only one will be randomly selected. The
inquirer will be responsible for taking the informed consent form confirming the eligibility
criteria that can be found below and assigning a unique ID number to each child. A baseline
questionnaire will be administered to record sociodemographic data such as date of birth,
gender, date of interview, and residence location. A thick blood smear will also be taken
upon participant recruitment. Follow-up visits at timepoints 7, 14, 21, 28, 42 days post
SMC-cycle start will be carried in selected households. The CHWs will invite the caregiver to
bring their children to the health facility on the specific day to collect the blood samples.
A short questionnaire exploring if the child received other treatment or experienced any
disease since SP+AQ administration will be administered every time a sample is taken during
the scheduled sample collection days (Day 0, 7, 14, 21, 28, 42). Heel (children aged 3-6
months) and finger (7-59 months) pricks will be collected for thick smears slides and DBS.
Dose, weight, age, mid-upper arm circumference, tympanic temperature, location, time, and
date will be recorded for each child on day 0, 7, 14, 21, 28 and day 42. All slides will be
stained by using the Giemsa method within 24 hours of collection at the closest health
facility and stored in a slide box with silica gel. Slides and DBS samples will be sent on to
MORU in Bangkok, Thailand for sample analysis, where they will be analysed using qPCR
methodology to detect drug concentrations, low-level sub microscopic parasitaemia and SP and
AQ resistance markers.12 Drug concentration processing will take place for all SMC drugs on
days 7, for sulfadoxine and AQ for day 28 and only for AQ for day 42 (as all the other drugs
will have been metabolized by then ). Individual surveys on day 42 after the final DBS is
taken will be conducted to determine if the child received other treatment or experienced
illness over the past month of study implementation. In the event these children become
febrile and receive a confirmed RDT between day 0 and day 42, they will have an additional
DBS taken.
Data analysis. Once the samples have been analysed, the MORU laboratory will send the
processed data back to the focal point at MC where the relevant mutations distributions and
proportions will be analysed comparing parasitological efficacy between groups of mutations.
Descriptive statistics of the intervention and control groups' drug levels will be calculated
for the determination of any correlations with treatment outcomes, in particular drug
concentrations on day 7. The focus will be on outliers with low levels of drug concentration
based on the metrics described. Day 28 positivity will be correlated to antimalarial drug
resistance genotype. Chemoprevention failure rates can be reported on as the cumulative
failure rate using Kaplan-Meier analysis of the proportion. A time to event analysis will
also be conducted to indicate duration of SMC infection protection afforded when looking at
chemoprevention failures during follow up through slide and/or positive DBS samples.
Feasibility and acceptability component Outcomes. The outcomes of the qualitative study will
be recorded experiences, opinions and perceptions surrounding SMC, that will be recorded and
analysed through interviews and focus group discussions.
Sample size. The participants recruited for this study component will be purposefully
selected and fall under four main groups: caregivers of children eligible for SMC (2 FGDs),
community health workers involved in the administration of SMC (2 FGDs), community members of
recognized importance and respect in areas where SMC is implemented such as community leaders
(5 KIIs), and key informants involved in SMC implementation, programme management and policy
making (4KIIs).The exact number of FGDs and KIIs will depend on data saturation in each of
the implementation scenarios.
Recruitment and data collection. Key informants for IDIs will be purposefully identified
during a stakeholder analysis done prior to the start of the study. For the FGDs,
sensitisation meetings will be conducted in each village by the research coordinator and the
county health official and head of villages to discuss the aims of the research, what it will
involve and if they are willing to allow villagers to participate. Research assistants will
visit villages and purposively recruit caregivers in consultation with village leaders based
on availability and willingness to participate, as communicated to the village leader. CHWs
will be purposively identified at HFs in collaboration with the head of the facility based on
their availability and willingness to participate in an FGD. The FGDs will be conducted in a
quiet and neutral space previously elected by the research team, and the research assistants
will work with the community leaders to keep the space private for the duration of the FGD.
All interviews and FGDs will be audio recorded following participants' consent, and will then
be transcribed and translated verbatim, or using equivalent translation where more
appropriate for maintaining the integrity of meaning.
Data analysis. Data collection and analysis will be conducted iteratively, with data analysis
beginning at the point of data generation. Participant recruitment and topic guides being
adapted after piloting, to confirm or refute hypothesis based on emerging findings, and
potential discrepancies from majority themes. Both inductive and deductive coding approaches
will be used for thematic analysis.
