Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05323721 |
| Other study ID # |
SMCUGPHASE2 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
December 1, 2023 |
Study information
| Verified date |
October 2023 |
| Source |
Malaria Consortium |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To-date, seasonal malaria chemoprevention (SMC) has only been scaled up across the Sahel
region of west and central Africa, primarily because of concerns over widespread resistance
to sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) in east and southern Africa. There are
increasing calls for this successful intervention to be used more widely and aggressively,
including in areas of east and southern Africa where malaria transmission is seasonal. To
test the feasibility, acceptability and impact of SMC with SPAQ in new geographies outside of
the Sahel, Malaria Consortium, together with the malaria programmes in Mozambique and Uganda,
is conducting implementation studies in both countries. The studies comprise two phases, with
the first phase focusing on acceptability and feasibility, followed by more rigorous
assessments of the effectiveness of the intervention and chemoprevention efficacy of the
medicines used in SMC.
Phase 1 of the studies has been successfully completed. The studies showed that SMC with SPAQ
was safe, acceptable and feasible, with very high coverage achieved among the target
population.Phase 2 of the SMC implementation study in Uganda will include study components
exploring the effectiveness of SMC with SPAQ and dihydroartemisinin-piperaquine (DP), as well
as the chemoprevention efficacy of DP when used in SMC. The study will be conducted in five
districts of Karamoja region. It will involve SMC delivery to around 142,000 children. The
majority of the target population will receive SPAQ, but around 15,000 children will receive
DP. Five monthly SMC cycles will be implemented between May and September 2022. As the
protective period of SPAQ and DP are comparable, monthly administration cycles will be
implemented irrespective of the drug regimen used.
Description:
The study aims to test the effectiveness and chemoprevention efficacy of seasonal malaria
chemoprevention (SMC) with sulfadoxine-pyrimethamine (SPAQ) and
dihydroartemisinin-piperaquine (DP) in the Karamoja region of Uganda. Specific objectives
are:
1. to determine the effectiveness of SMC using SPAQ and DP;
2. to determine the chemoprevention efficacy of SPAQ and DP when used for SMC;
3. to investigate the presence and change of SPAQ and DP resistance markers over time as a
result of SMC implementation;
4. to evaluate the process of SMC implementation, including coverage, quality of SMC
implementation, costing, feasibility and acceptability, as well as an assessment of the
role of gender in SMC implementation.
Study design This type 2 hybrid effectiveness-implementation study uses a convergent
mixed-methods approach. SMC will be implemented in five monthly cycles between June 2022 and
October 2022 in five districts of Karamoja. Table 2 provides an overview of the study
components, as well as where and when they will be conducted, as well as the implementing
partner and the proposed funding source.
Table 2. Uganda SMC implementation study phase 2: study components. Study component Primary
outcome Objective Location Timing Implementing partner Funding Cluster randomised controlled
trial Clinical malaria 1 Amudat May 2022 (baseline) and October 2022 (endline) Malaria
Consortium Philanthropic Malariometric survey Malaria prevalence 1 Amudat May 2022 (baseline)
and October 2022 (endline) Malaria Consortium Philanthropic Chemoprevention efficacy cohort
study Chemoprevention failure Drug concentrations and drug resistance genotypes among
chemoprevention failures 2 Nakapiripirit May/June 2022 (28 days following distribution of the
first monthly SMC cycle) IDRC Bill & Melinda Gates Foundation Resistance markers study
Prevalence of antimalarial resistance markers 3 Amudat, Kotido, Moroto, Nabilatuk,
Nakapiripirit April 2022 (baseline) and November 2022 (endline) IDRC Bill & Melinda Gates
Foundation End-of-round household survey Coverage and quality of SMC implementation 4 Amudat,
Kotido, Moroto, Nabilatuk October 2022 Malaria Consortium Bill & Melinda Gates Foundation
Cost-effectiveness analysis Cost-effectiveness 4 n/a November 2022 Malaria Consortium
Philanthropic Key informant interviews and focus group discussions Feasibility and
acceptability of SMC implementation 4 Amudat, Kotido, Moroto, Nabilatuk August-October 2022
Malaria Consortium Bill & Melinda Gates Foundation Methods
Malaria Consortium seeks funding from the Bill & Melinda Gates Foundation for the following
study components:
Chemoprevention efficacy cohort study While the detailed methods of the chemoprevention
efficacy cohort study are described in the related proposal submitted by IDRC as the main
implementing partner of this study component, Malaria Consortium will supervise the
distribution of SMC medicines and coordinate community sensitisation activities. Some costs
relating to this study component have therefore been included in Malaria Consortium's grant
request. Malaria Consortium will also manage the relationship with Mahidol-Oxford Research
Unit (MORU) in Bangkok, Thailand, the laboratory that will process the samples collected for
this study component. The costs relating to sample processing by MORU have therefore also
been included in this grant request.
End-of-round household survey At the end of the SMC round, a comprehensive household survey
based on a multi-stage sampling protocol will be conducted to obtain representative data on
coverage across the intervention area, as well as quality aspects such as implementers'
adherence to SMC guidelines. The survey will be conducted in all four districts (all except
Nakapiripirit), as only 1,000 children enrolled in the chemoprevention cohort study will
receive SMC in that district. It uses a cross-sectional cluster-randomized sampling approach
to target caregivers of children aged 3-119 months who were resident in the study location
during the SMC implementation period. The sampling protocol aims to achieve a self-weighted
sample with sampling units selected with probability proportional to size. Only at the last
stage of sampling, i.e., at the household level, will a constant number of eligible children
(one child per household) be selected. The survey will be powered to give an estimate of SMC
coverage for children aged 3-59 months with a margin of error of 5%, while also providing a
representative sample of children aged 60-119 months (based on the assumption of an
intraclass correlation coefficient of 0.23). This will require a sample of 120 clusters, each
comprising 15 children (n=1,800), randomly selected from areas with SMC delivery across the
four districts with probability of selection proportional to population size.
The main objective of the survey is to determine if children received the full three-day
course of SPAQ or DP during each cycle of the SMC round. Other coverage indicators the survey
will measure for each cycle include:
- Proportion of households with eligible children visited by a community distributor in
each cycle
- Proportion of Day 1 SPAQ and DP administered by community distributors to eligible
children
- Proportion of eligible children who received a full three-day course of SPAQ or DP
- Proportion of Day 1 SPAQ and DP administered observing DOT The survey will also explore
indicators relating to quality of SMC implementation and adherence to the SMC protocol,
such as the proportion of children above the age of five who receive SMC despite not
being eligible and the proportion of children who are correctly re-dosed if they vomit
or spit out the medicines within 30 minutes of first administration. In addition, the
survey will gather data on gendered intra-household dynamics and other gender issues,
including household composition (e.g., female-headed/male-headed household, sex of the
primary caregiver), as well as roles in health-related decision-making.
Data will be collected using a survey questionnaire developed by Malaria Consortium and
translated into relevant local languages, using the SurveyCTO software application that will
enable direct, field-based computer-aided personal interview (CAPI) and remote capture of the
data and transfer to a netbook computer. All survey tools will be pre-tested. Daily quality
assurance checks will be carried out during the field work. Data will be analysed using Stata
16. All indicators of interest will be calculated in proportion by district and an average
across all districts. The 95% confidence interval, with correction for survey design effect,
will be used to provide a range of values around the estimate within which selected result
will be expected to fall. Data analysis will also involve testing the association of
gender-related variables with SMC outcomes measured by the surveys (e.g., adherence to the
three-day SPAQ regimen).
Key informant interviews and focus group discussions
To understand perceptions of the feasibility and acceptability of the intervention among a
range of stakeholders, key informant interviews (KIIs) and focus group discussions (FGDs)
will be conducted during the later stages of SMC implementation and immediately after the end
of the annual SMC round. Participants will fall into four main categories:
1. Caregivers of children eligible for SMC
2. VHTs and health workers involved in SMC delivery
3. Community members in areas where SMC is implemented
4. Programme managers, policy makers and civil society organisations, including gender
experts Purposive sampling will ensure that both female and male participants, as well
as participants from all study districts are selected, except Nakapiripirit where only a
small number of children will receive SMC as part of the chemoprevention efficacy study.
Other social determinants such as rural/urban and participants' age will also be taken
into account. A mix of KIIs and FGDs will be conducted until data saturation is reached,
i.e. until further data does no longer generate new findings relating to the topic of
investigation.[8] The total sample size can therefore not be determined at this stage.
We estimate that around five participants per relevant category will be recruited for
KIIs and that at least four FGDs comprising six to eight participants each will be
conducted with participants from categories a, b and c. Typically, separate FGDs will be
conducted for male and female participants.
Qualitative data will be collected by trained research assistants who are fluent in relevant
local languages. Data collection will be facilitated by topic guides to explore views about
SMC and reflections on the implementation experience. Topic guides for different categories
of participants will focus on different areas of interest that are expected to be most
relevant for the different types of respondents. The role of gender and the experiences of
participants of different genders will be explored in detail with all respondent categories.
This will include discussion of gender barriers and gender gaps, as well as health-related
decision-making power. A gender analysis framework developed by Jhpiego will be adopted for
this purpose.
Topic guides will be developed for all participant categories. However, the guides will only
serve as prompts for the data collector. KIIs and FGDs will generally be participant-led,
providing opportunities to discuss topics not covered by the topic guide. All KIIs and FGDs
will be audio-recorded and research assistants will take notes, including on non-verbal cues.
Data analysis will be conducted iteratively, beginning at the point of data generation, and
with participant recruitment and topic focus being adapted as data collection progresses to
further test emerging concepts, as well as potential discrepancies from majority themes.
