Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06182176 |
| Other study ID # |
29839 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 27, 2024 |
| Est. completion date |
January 12, 2026 |
Study information
| Verified date |
December 2023 |
| Source |
London School of Hygiene and Tropical Medicine |
| Contact |
Muhammed O AFOLABI, MD, MPH, PhD |
| Phone |
+447535954947 |
| Email |
Muhammed.Afolabi[@]lshtm.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Malaria remains a major health problem, especially among children living in sub-Saharan
Africa where more than 90% of the disease and deaths occur. Adding to this high burden among
the children is the co-existence of parasitic worms in their intestines and urinary tract.
The combined infection of malaria and parasitic worms in these children has additive adverse
effects of anaemia, poor physical and cognitive development, and death. Existing control
programmes for the parasitic worms are operating sub-optimally despite the 2012 London
Declaration on Neglected Tropical Diseases (NTDs) of achieving 75% treatment coverage by
2020. On the other hand, a malaria prevention programme, called Seasonal Malaria
Chemoprevention (SMC), introduced in the same year as the London Declaration on NTDs has
achieved more than 75% treatment coverage and prevented 75-85% of cases of uncomplicated and
severe malaria in children. The remarkable success of SMC has led to the recent WHO
recommendation for its extension to other at-risk age groups and in highly seasonal malaria
transmission settings outside the Sahel region. This encouraging development supports the
need to explore the possibility of integrating helminth control programmes with other
successful delivery platforms such as SMC. However, limited empirical evidence exists on an
integrated approach that integrated the control of malaria and parasitic worms in a safe,
acceptable, easy-to-deliver and effective manner.
To address this knowledge gap, the investigators conducted a randomised controlled trial in
the first stage of this project to establish the feasibility and safety of integrating
helminth control with SMC among Senegalese children. This second stage will assess the
effectiveness and cost-effectiveness of using SMC platform to deliver deworming drugs to
preschool and school-aged children living in communities where the burden of malaria and
parasitic worms is high in central Ghana. One thousand, two hundred children aged 1-14 years
will be randomly assigned equally to two study communities where antimalarial (SMC) drugs and
deworming drugs will be administered in combination to the children living in one study
community, and antimalarial (SMC) drugs alone will be delivered to the children living in the
second study community. The effectiveness of the combined delivery will be determined by
checking whether the combined antimalarial and deworming drugs prevent anaemia in the
children who receive the combined drugs compared to the children who receive antimalarial
drugs only. We will also determine the cost and cost-effectiveness of this approach by
estimating the incremental cost savings due to cases of moderate and severe anaemia averted
by giving antimalarial and deworming drugs together to the children. The findings of this
study would provide evidence to boost public health recommendations for an integrated control
of malaria and parasitic worms among children living in the poorest countries of the world.
The findings may also reinforce the empirical evidence that the future direction of
healthcare systems in developing countries should be comprehensive health management rather
than vertical management of a single disease.
Description:
This study has two components: effectiveness and cost-effectiveness components. The
effectiveness study will be conducted in three stages. The first stage will focus on
pre-intervention surveys in Kintampo North Municipal and Pru East district. This will be
followed by an intervention stage which will be conducted in either Kintampo North or Pru
East district, depending on which of these districts has a higher prevalence of malaria, STH
and schistosoma infections. The third stage will be a post-intervention cross-sectional
survey in the communities where the intervention study is conducted.
First stage: During community sensitisation and engagement meetings with parents and
caregivers of potentially eligible children living in Kintampo North Municipal and Pru East
district, the Kintampo Health Research Centre (KHRC) study team will explain the need for
this study, using a simple picture to illustrate the integration of SMC and anthelminthic
drugs; the study rationale and informed consent procedure, and the risks and benefits of
allowing their children to participate in the study. After these meetings, an investigator
from KHRC will identify parents/caregivers of potential child participants to explain the
study further to them on an individual basis. The parents/caregivers will be given a copy of
the participant information sheet. Parents/caregivers who feel that the study is appropriate
for their child will be visited at home at a mutually agreed time. For logistical purposes,
written informed consent will be obtained from a parent/caregiver one day before the planned
start date of the pre-intervention survey in both districts, along with positive assent from
children aged ≥ 7 years, where required. Following this, an investigator will provide a
pre-labelled stool collection container to the parent/caregiver at this visit and encourage
them to collect stool from their child and keep this safely for the research team who will
visit them the following day. Subsequently, the investigator will confirm the
parent/caregiver's willingness to allow their child's continued participation in the study
and administer a purpose-designed electronic questionnaire to the parents/caregivers. The
questionnaire will cover information such as socio-demographic data, health and residence
characteristics, history of de-worming and malaria treatment. Height/length (cm) and weight
(kg) of each child will be measured and anthropometric indices height-for-age,
weight-for-age, weight-for-height, and body mass index, will be calculated using the WHO
AnthroPlus software (www.who.int/growthref/tools/en/). The study villages will be mapped by
recording each study participant's household global-positioning system (GPS) coordinates with
a hand-held GPS device.
Following administration of the questionnaire, finger-prick blood samples will be collected
from each child participant for thick and thin smear examination for malaria microscopy, and
blood spot filter papers will be collected for DNA isolation and PCR amplification for
species determination. Haemoglobin concentrations will be measured using the Haemocue®
method. Freshly voided urine samples will also be collected from all study children. Urine
filtration test will be used to quantify S. haemotobium, according to standard laboratory
guidelines. Parallel testing for circulating cathodic antigens (CCA) will be used to
complement the filtration test.
Stool samples will be collected to detect intestinal helminths. Duplicate Kato-Katz thick
smears will be prepared from the stool samples and examined by experienced technicians using
light microscopy to determine the egg counts for S. mansoni and STH. The number of eggs per
slide will be used to obtain a measure of the number of helminth eggs per gram of faeces
(EPG). The intensity of the helminth infection will be categorised according to standard
guidelines. A multiplex PCR assay will also be used for simultaneous detection of mixed
infections of helminths. Quality control will be performed by re-examining at least 10% of
randomly selected blood slides, urine filters and Kato-Katz smears by an experienced
independent laboratory scientist. Laboratory staff performing the analyses will be masked to
the origin of the samples.
Intervention stage: The intervention stage will be implemented during SMC campaign in Bono
East Region. Results obtained from the laboratory analysis of the blood, stool and urine
samples collected from the children enrolled in the pre-intervention surveys in Kintampo
North and Pru East districts will be used to determine which of the districts will host the
intervention stage of the study. Given that the focus of this project is to evaluate the
effectiveness of the integrated SMC-NTD control programmes, the intervention stage of the
study will be conducted in the district with a higher prevalence of malaria, STH and
schistosomiasis. Also, the intervention stage will be implemented in conjunction with the SMC
providers in the selected district. The first day of starting the intervention stage (Day 0)
will correspond to the day prior to the commencement of the first cycle of SMC in the
selected district. On that day, the communities in the selected district will be randomised
at the community level and stratified on the basis of the malaria and helminth prevalence
(obtained from the pre-intervention surveys) into two groups at a 1:1 ratio to receive either
combined SMC and anthelminthic drugs (intervention arm) or SMC drugs only (control arm).
Given that 4-aminoquinoline drugs are reported to have antagonistic pharmacological
interactions with praziquantel, the SMC partner drugs, amodiaquine AQ (a 4-aminoquinoline
derivative) and sulphadoxine-pyrimethamine (SP) will not be administered with anthelminthic
drugs (albendazole and praziquantel) on the same day in this study. Therefore, eligible
children randomised into the intervention communities will receive albendazole and
praziquantel on Day 0 and those randomised into the control communities will receive Vitamin
A and Zinc supplements as control drugs. On the following day which corresponds to the start
(Day 1) of the first SMC cycle, the children in the control and intervention communities will
receive AQ and SP according to the WHO and Ghana SMC implementation guidelines. This will be
followed on the second and third day of the SMC cycle with all study children in the two
groups receiving AQ, in line with the SMC guidelines. All children irrespective of the study
arms will undergo safety assessment.
Post-intervention stage: All child participants enrolled in the intervention study will be
evaluated one month after the last course of SMC cycles, which corresponds to the end of
malaria transmission season, to measure their haemoglobin concentration and to obtain a
further blood film, dried blood spot, stool and urine samples, to test for malaria-helminth
co-infections using parasitological methods such as microscopy, Kato-Katz, urine filtration
test and improved diagnostic tools including molecular methods (qPCR), as described above.
Data collection for the cost and cost-effectiveness analyses: The incremental financial and
economic costs of delivering the integrated SMC-anthelminthic drugs programme in the
intervention stage of this study will be estimated from a health service (Ministry of Health
and donor) perspective, compared to the counterfactual of giving SMC drugs alone. Financial
cost data (including all direct expenditures on the trial including salaries) and economic
costs (donated goods or services, such as time of salaried health workers) will be collected
through reviews of project records and semi-structured key informant interviews (KIIs) at
district, health facility and community health workers (CHW) levels. Detailed costs will be
captured for disaggregated cost categories, including SMC and MDA drugs; drug supply chain;
CHW delivery of doses; supervision; training; planning meetings; sensitisation; and supplies.
Incremental costs required for the integrated delivery of anti-helminth MDA with SMC above
what would be required for SMC delivery alone will be identified. The cost of diagnosis and
treatment of moderate and severe anaemia from the health service perspective will be
estimated using a combination of primary and secondary data. Cost per outpatient visit and
cost per inpatient day (excluding diagnosis and treatment) will be obtained from existing
data sources. Costs of diagnostic tests, medicines and provider time for treating cases of
moderate and severe anaemia will be captured through KIIs with health staff at facilities
providing outpatient and inpatient services in the study area. These parameters will be used
to estimate incremental cost savings due to cases of moderate and severe anaemia averted by
SMC plus MDA compared to SMC alone.
For the cost-effectiveness analysis (CEA), the main measure of the effects will be
disability-adjusted life-years (DALYs) averted. DALYs combine mortality (years of life lost,
YLLs) and morbidity (years lived with disability, YLDs) into a single measure of effect,
allowing the impact of SMC + MDA to be compared with the impact of different types of health
interventions. The effect measure used to calculate DALYs will be moderate and severe anaemia
cases averted (where anaemia is the primary outcome for the CEA which is where the main
incremental health benefit from co-delivery is expected), derived from unadjusted results of
the trial, calculated on the basis of intention-to-treat. DALYs will be modelled using a 3%
discount rate in the base case, no age weighting, standard DALY weights and life tables, and
other secondary data (e.g. duration of an episode of anaemia). The CEA results will be
expressed as an incremental cost-effectiveness ratio (ICER). The ICER is calculated as the
difference in costs between MDA + SMC versus SMC alone, divided by the difference in effects
between those strategies.
