Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05285657 |
| Other study ID # |
TMA2019CDF 2697 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 28, 2022 |
| Est. completion date |
November 30, 2023 |
Study information
| Verified date |
March 2022 |
| 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
In Sub-Saharan Africa (SSA), fever remains a major public health problem in children. The
introduction of malaria rapid diagnostic tests (RDTs) in routine healthcare has greatly
improved the management of malaria. However, despite the good attitude of healthcare workers
to adhere to malaria RDT test results, persisting hrp2antigen and low sensitivity of pLDH RDT
negatively affect antimalarials and antibiotics prescriptions practices. This is one of the
main causes of antimicrobial resistance (AMR) and inappropriate management of febrile
diseases. To improve the diagnosis of febrile diseases and subsequent prescription of
antimicrobials, it is hypothesized that the implementation of an algorithm including a
two-step malaria RDT PfHRP2/pLDH supported by point-of-care tests (POCTs) for C-reactive
protein, oximetry, and bacterial infection such as Group A Streptococcus, and
Salmonella/Shigella, will significantly improve the management of febrile diseases and
thereby tackling AMR.
To assess the value of the proposed algorithm, an open-label randomized controlled trial with
three arms, enrolling febrile children under 5 years is proposed.
- In the control arm, febrile children will benefit from a complete clinical examination.
Treatment will be done according to the national guideline.
- In RDTs decisional algorithm (RDT-DA) arm (intervention), the complete clinical
examination will be supported by two-step malaria RDT and bacterial infections RDTs.
Prescription will be left to the discretion of the healthcare workers.
- In e-algorithm arm (intervention), the complete clinical examination and the outcomes of
RDTs (malaria and bacterial infections) will be digitalized. Diagnostic and prescription
will be done by the algorithm.
A final follow-up visit (day7) will be scheduled for all participants. Patients will be asked
to return to the health facilities in case of no improvement.
Primary study outcomes will be the proportion of curative case and antimicrobial(s)
prescribed in each arm. Secondary outcomes include: (i) adherence of healthcare workers to
the algorithm; (ii) adherence of parents/guardian to treatment; (iii) accuracy of the
algorithm for the diagnostic of malaria.
This project will serve as a path of policy change in the management of febrile diseases and
AMR. By relying on existing RDTs available, the implementation of this algorithm will tackle
AMR and provide better care. If successful, the project will equip the lead applicant to
establish himself as an independent researcher with ability to further build his own research
team. The project will also offer training opportunities to young scientists, and further
strengthen already existing capacities of the home institute.
Description:
Background In Sub-Saharan Africa (SSA), febrile illnesses remains a major public health
problem in children. The introduction of malaria rapid diagnostic tests (RDTs) in routine
healthcare has greatly improved the management of malaria. However, despite the good attitude
of healthcare workers to adhere to malaria RDT test results, persisting hrp2 antigen and low
sensitivity of pLDH RDT negatively affect antimalarials and antibiotics prescriptions
practices. These limitations of the RDTs lead to poor management of febrile diseases and
antimicrobial resistance (AMR). To improve the diagnosis of these febrile diseases and
subsequent prescription of antimicrobials, it is hypothesized that the implementation of an
algorithm including a two-step malaria RDT PfHRP2/pLDH supported by point-of-care tests
(POCTs) for C-reactive protein, white blood cells (WBC) count, urine dipstick, oximetry, and
bacterial infection such as Group A Streptococcus, and Salmonella/Shigella, will
significantly improve the management of febrile diseases and thereby tackling AMR.
Methodology To assess the value of the proposed algorithm, an open-label randomized
controlled trial with three arms, enrolling febrile children from 2 to 59 months is proposed.
- In the control arm, febrile children will be managed according to the IMCI (integrative
management of childhood illnesses) and the guideline of diagnostic and treatment (GDT),
which are part of the routine system existing in Burkina Faso. Treatment will be done
according to the national guideline.
- In RDTs decisional algorithm (RDT-DA) arm (intervention), the clinical examination based
on IMIC will be supported by two-step malaria RDT and bacterial infections RDTs.
Prescription will be left to the discretion of the healthcare workers.
- In e-algorithm arm (intervention), artificial intelligence integrating multiple layers
of clinical information such as clinical examination, signs/symptoms and medical
history, and laboratory information such as outcomes of biomarkers (CRP and WBC) and
pathogen specific POCT (malaria and bacterial infections) and oximetry will be
developed. The e-algorithm will serve to guide the diagnostic and management of febrile
infections in children from 2 to 59 months.
In the 3 arms, the supports of data collection will be digitalized. A final follow-up visit
(day7) will be scheduled for all participants. Patients will be asked to come back to the
health facilities before scheduled visit if the symptoms persist or health condition
worsening.
Study Duration This is estimated to be 36 months from the start of the study. The first 12
months will be reserved for the development of the algorithm (artificial intelligence) of
e-Algorithm arm and the study CRFs for RDT-DA and control arms.
Study sites The study site will be the Health District of Nanoro, specifically the health
facilities of Siglé and Pella in Burkina Faso.
General objective To evaluate the value of the diagnostic performance of the proposed
algorithm combining two-step malaria RDT detecting PfHRP2/pLDH and POCT for the diagnostic of
malaria and bacterial infections respectively, in the management of febrile illnesses in
children from 2 to 59 months in a process of Universal Health Coverage (UHC).
Specific objectives Primary objective
1. To assess the impact of the proposed strategies on the acute fever management practice
at primary health facilities;
2. To assess the impact of the proposed strategies on the antimalarial and antibiotic
prescription practices at primary health facilities;
3. To assess in randomized superiority diagnostic trial the curative rate whether the RDTs
decisional algorithm (RDT-DA), e-Algorithm or routine system and to determine which one
allow to access to quality health cares at primary health facilities.
Secondary objectives
1. To assess the accuracy of the algorithm based on (i) two-step malaria RDT detecting
PfHRP2/pLDH for the diagnosis of malaria infection compared to microscopy and polymerase
chain reaction (PCR); (ii) and POCT for the diagnostic of bacterial infections compared
to bacterial cultures.
2. To assess the adherence of health care workers and parents/guardian to the algorithm
proposed;
3. To assess the adherence of the health care workers and parents/guardian to the
prescription in RDT-DA, e-Algorithm and control arms;
4. To assess the safety of the algorithm in the management of febrile cases in children
presenting in outpatient clinic.
Study Population Study participants (children from 2 to 59 months of age) will be identified
during their visit to the study health facilities for simple febrile illnesses. Children from
2 to 59 months years of age (with parents/guardians able to give a consent) attending the
health facilities where the study will be carried out and who fulfil the inclusion criteria
will be asked to participate in the study and to give written informed consent.
Study outcomes Primary study outcomes will be the proportion of recovered case and
antimicrobial(s) prescribed in each arm. Secondary outcomes include: (i) adherence of
healthcare workers to the algorithm; (ii) adherence of parents/guardian to treatment; (iii)
accuracy of the algorithm for the diagnosis of malaria and others POCT to guide bacterial
infections (biomarkers and pathogen-specific POCT).
Sample size Sample size is calculated based on data collected in the consultation book of the
health facilities of Sigle and Pella. From these data collected in 2018 (January to
December), the proportion of febrile children under 5 years presenting at the health
facilities with febrile illnesses and who were prescribed antibiotic was 62,63%. The
implementation of the algorithm is expected to reduce this proportion to at least 20%. In
this study the sample size is computed to a Bonferroni correction of alpha is performed for
multiple comparisons, therefore, an alpha level of 0.017 is chosen. Type II error was
controlled at 20% i.e. (β=0.20 or 80% power). Based on these parameters, a sample size of 356
is required per arm. Hence, an overall sample size for the study is estimated at 1068
(3×356). Further assuming that 10% of the individuals will be lost to follow-up, an adjusted
sample size of 392 children per arm is required. The final estimated sample size for this
study is thus 1176 children.
Statistical analysis An analyses plan of the data will be developed and validated by the
participants of the first workshop of the project, prior the recruitment of the first study
participant. This analyse plan could be revised according to events and in case of amendment
of the protocol. The statistical analysis will be done with an appropriate data analysis
software (STATA 14.1. and R).
