Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04238845 |
| Other study ID # |
TMA2018CDF-2365 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 13, 2020 |
| Est. completion date |
March 2022 |
Study information
| Verified date |
March 2021 |
| Source |
Institut de Recherche en Sciences de la Sante, Burkina Faso |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Malaria and malnutrition represent major public health concerns worldwide especially in
Sub-Sahara Africa. Despite implementation of Seasonal Malaria Chemoprophylaxis (SMC), an
intervention aimed at reducing malaria prevalence among children aged 6- 59 months, the
burden of malaria and associated mortality among children below age 5 years remains high in
Burkina Faso. This raises the question of what hiding factors may negatively affect the
responsiveness of SMC intervention. Malnutrition, in particular micronutrient deficiency, is
one of these potential factors that can negatively affect the effectiveness of SMC. Treating
micronutrient deficiencies is known to reduce the prevalence of malaria mortality in highly
prevalent malaria zone such as rural settings. Therefore, the hypothesis that a combined
strategy of SMC together with a daily oral nutrients supplement (Vitamin A-Zinc OR fortified
peanut butter-like paste-Plumpy'Doz) will enhance the immune response and decrease the
incidence of malaria in this population and at the same time reduce the burden of
malnutrition among children under SMC coverage was postulated.
Prior to the SMC implementation by the National Malaria Control Program (NMCP), children
under SMC coverage will be identified through the Health and Demographic Surveillance System
(HDSS). Children will be randomly assigned to one of the three groups (a) SMC + Vitamin A
alone, (b) SMC + Vitamin A+ Zinc, or (c) SMC+Vitamin A + Plumpy'Doz. After each SMC monthly
distribution, children will be visited at home to confirm drug administration and follow-up
for one year. Anthropometric indicators will be recorded at each visit. Blood samples will be
collected for thick and thin film and hemoglobin measurement and spotted onto filter paper
for further PCR analyses.
This project will serve as a pilot of an integrated strategy in order to mutualize resources
for best impact. By relying on existing strategies, the policy implementation of this joint
intervention will be scalable at country and regional levels.
Description:
Malaria is hyper-endemic in Burkina Faso and many sub-Saharan Africa countries. According to
the National Malaria Control Program (NMCP) approximately 11 915 816 malaria cases and 4 144
malaria-related deaths were reported in 2017 in Burkina Faso. Numerous malaria control
interventions have been implemented in Burkina Faso in order to achieve the 2030 Sustainable
Development Goal (SDG) 3. Seasonal malaria chemo-prevention (SMC) ranks among the largest and
reliable interventions for malaria control in countries with marked seasonality of malaria
transmission. This preventive measures involves administering antimalarial drugs
(Amodiaquine-Sulfadoxine-Pyrimethamine) to children aged 6- 59 months on a monthly basis
during the high transmission peak. In Burkina Faso, SMC is implemented from July/August to
October/November each year. SMC is recommended by the World Health Organization (WHO) and is
known to reduce malaria morbidity by 30 to 80%. Despite the implementation of this strategy,
the burden of malaria and associated mortality is still very high in this population in
Burkina Faso. This raises questions about other hidden factors that can negatively affect the
effectiveness of SMC intervention.
At the same time, malnutrition is a major cause of childhood morbidity and mortality in low-
and middle-income countries such as Burkina Faso. Malnutrition can lower immune system
leading to increased severity of malaria in the population. The National Nutrition Program
(NPP), which is the agency established to address malnutrition problems in Burkina Faso,
currently aims to scale-up Community Management of Acute Malnutrition (CMAM). Both malaria
and malnutrition are highly prevalent in rural settings. Furthermore, malaria seasonal peak
coincides with period of food crisis in the country suggesting that malnutrition may
influence malaria incidence during that period. Children under five years again represent the
most vulnerable group. Importantly, treating micronutrient deficiencies is known to reduce
malaria morbidity and mortality. Plumpy'Doz is specifically formulated for prevention of
malnutrition in children from 6 months of age and adults. It has been recommended since 2007
by the WHO, UN Children's Fund (UNICEF), World Food Program (WFP), and the UN Standing
Committee on Nutrition in the joint declaration on community-based management of severe acute
malnutrition. Evidence also shows that Vitamin A-Zinc supplementation reduce malaria
morbidity. A reduction by 20-30% of malaria incidence through micronutrient supplementation
such as Vitamin A-Zinc has also been reported.
These aspects underlie the idea of the SMC-Nutrition project. This combined strategy could
enhance the immune response and therefore decrease the severity of malaria in this population
and at the same time reduce the burden of malnutrition in children under SMC coverage. This
project will serve as a pilot integrated strategy in order to mutualize resources for best
impact. By relying on existing strategies, the policy implementation of this joint
intervention will be scalable at country and regional levels. If the pilot produces promising
results, a large-scale multi-centric assessment of the strategy will be performed in several
SMC countries (i.e. Niger, Mali and Burkina Faso).
Purpose and objective(s) Aim 1: To assess the feasibility of combining two different
strategies led by different programs (malaria and nutrition) which affect the same target
population (children under five years). SMC is a larger community-based intervention at a
national level led by the NMCP. National Nutrition Program is trying to scale up the
Community Management of Acute Malnutrition (CMAM). This project will serve as a pilot of
integrated strategy in order to mutualize resources for best impact. By relying on existing
strategies, the policy implementation of this joint intervention will be scalable at country
and regional levels.
Aim 2: To boost the impact of SMC intervention in terms of reducing malaria morbidity,
mortality and reduce the burden of malnutrition and anaemia in children under five years
through supplementation with micronutrients and Vitamin A-Zinc.
Primary objectives 1: to assess in a randomized superiority trial whether SMC + Vitamin A+
Zinc or SMC+ Vitamin A+ Plumpy'Doz is more effective and safe in reducing uncomplicated
malaria incidence, severe malaria incidence and related mortality compared to the SMC+
Vitamin A alone Primary objectives 2: to investigate the impact of the combined strategy in
reducing the burden of malnutrition through reduction of anaemia incidence, mid-upper arm
circumference gain, and weight gain.
Secondary objectives 1: to assess the impact of each treatment arm on the circulation
parasite population through monitoring the temporal trend of antimalarial resistance
molecular markers pfcrt, pfmdr1, dhfr and dhps.
Secondary objectives 2: to assess the coverage and compliance to SMC in the study area.
Secondary objectives 3: to determine the overall risk of adverse events (AEs).
Study population The target population is children under five years under SMC coverage and
living across HDSS area
Subgroup analysis Three subgroups will be defined: (i) SMC + Vitamin A alone (ii) SMC+
Vitamin A+ Zinc and (iii) SMC+ Vitamin A +Plumpy'Doz
Proposed sample size The overall sample size for the study was estimated at 882 (3×294) to
detect a 10% difference in risk of malaria occurrence between SMC alone group and any of SMC+
supplement group. Further assuming that 20% of the individuals will be lost to follow-up, an
adjusted sample size of 353 children per arm was required. The final estimated sample size
for this study is thus 1,059 children.
Trial design This is post-marketing phase. All the products that will be used in this study
are recommended by WHO and are already used as part of routine management of acute
malnutrition in Burkina Faso. Eligible children will be assigned to one of the three study
arms: (i) SMC + Vitamin A alone (ii) SMC+ Vitamin A + Zinc and (iii) SMC+ Vitamin A +
Plumpy'Doz. Administration of Amodiaquine-Sulfadoxine Pyrimethamine (AQ-SP) will not be
performed by the study team but by the NMCP.
Randomisation method A computer-based randomization system will be used to assign the
included children. The allocation will be performed at a central level (pharmacie of the
CRUN) by the pharmacist phone call (pharmacist-field workers) following the inclusion number.
Protection against sources of bias This will be an open label study. No blinding is planned.
However, to avoid contamination, only one child per household will be included.
Study duration Enrolment of participants will be implemented in parallel with SMC
implementation by the National Malaria Control Program (NMCP). The randomized children will
be followed-up actively for 6 Months and passively for six months to fully cover the high and
low transmission periods.
Product(s) to be tested All the products that will be used in this study are recommended by
WHO and are already used as part of routine management of acute malnutrition in Burkina Faso.
The study products include Vitamin A-Zinc and Plumpy'Doz. Administration of
Amodiaquine-Sulfadoxine Pyrimethamine (AQSP) will not be performed by the study team. SMC is
implemented by the NMCP and all children 6-59 months are expected to be covered. Vitamin A
supplemention will be performed by the Direction of Nutrition as a nationalwide campaign for
the prevention of malnutrition in children under five years of age.
Product supply The product will be supplied to the household fortnightly. The stock will be
ordered from accredited manufacturer according to the nutrition program of Burkina Faso.
Trial site selection The study will take place in Nanoro,Burkina Faso.
Recruitment and retention Prior to SMC first Round, children under five years living across
HDSS area will be identified from the dataset of the last update round. Potential study
participants will be randomly drawn from this list of children. Home visit will be performed
to confirm the presence of the child, notify and inform parents of eligible participants
about study and where possible obtain informed consent. Absent children or children whose
parents are not willing to participate, will not be considered and will be replaced by other
eligible children from the list. Children will be included after confirmation of the
administration of the first dose of SMC Round 1 and after written consent is provided by the
parents or guardians. Included children will be randomly allocated to one of the three study
arms: (i) SMC + Vitamin A alone (ii) SMC+ Vitamin A+ Zinc and (iii) SMC+ Vitamin A +
Plumpy'Doz. In case of many eligible children within a household, only one child will be
included in order to avoid contamination between test and control groups. The randomized
children will be followed-up actively for six Months and passively for six the next six
months.
Trial subject safety All the products that will be used in this study are recommended by WHO
and are already used as part of routine management of acute malnutrition in Burkina Faso.
Health service research issues, health economics and/or quality of life measures The project
will promote economic development and welfare in Burkina Faso: the outcomes of this project
will contribute indirectly to the economic development by reducing the burden of malaria and
malnutrition, which constitute significant threats to economic development in the country.
Patient and/or community involvement The project will involve key stakeholders (Household and
families of children, community health workers, health professionals, policy makers and
representative of local community) at all levels of the health system in Burkina Faso through
regular meetings.
Trial Steering Committee Prior to the study start, a trial steering committee will be set.
This committee will comprise five independent members: a pediatrician, a nutritionist, a
member of the Nanoro health district executive team, representatives of the national malaria
and nutrition programs. The committee will monitor the progress of the trial through regular
teleconferences and physical meetings (twice during the course of the intervention), advice
on the scientific credibility and on specific issues that may arise during the course of the
study. All decisions taken by this committee will be made by majority vote and will be
documented.
Data Safety Management Board (DSMB) There will be no DSMB. Regular feedback on the
effectiveness and safety of the combined intervention will be made available to local and
national drug regulatory authorities within the Nanoro site and at the country level. When
children under SMC coverage are missed, local health authorities will be informed
immediately.
Trial Monitoring IRSS will contract an independent monitor and ensure that the study is
adequately monitored. The monitor will verify the best conduct of the study through phone
calls with the principal investigator and other study staff. Two monitoring visits are
planned: an initiation visit before the enrolment of the first participant and a close-out
visit after the last patient has completed the follow-up.
Ethical and regulatory approval The study protocol will have the approval of the Ethics
Committees for Health Research in Burkina Faso prior to the start of the study.
