Evaluation of a new and simple diagnostic test for malaria
| ISRCTN | ISRCTN13334317 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13334317 |
| Secondary identifying numbers | PACTR202202766889963 |
- Submission date
- 19/01/2022
- Registration date
- 22/02/2022
- Last edited
- 17/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Malaria is the most important parasitic disease worldwide. The disease is caused by the malaria parasite which dwells in the blood of infected patients. It is important to find out if a case is infected as immediate treatment with the right drugs is important to circumvent death or severe disease. Current tests (diagnostic tests, like microscopy or rapid diagnostic tests) to detect the malaria parasite in blood have limitations. They may not be sensitive enough (do not detect the parasite; they are “false negative”) or remain positive after successful treatment (“false positive”). A molecular diagnostic test based on the detection of parasite genetic material (DNA) might be much better, but their use in resource-limited countries (like many countries in Africa), because they require sophisticated equipment and a constant supply of electricity.
Our project has developed a simple molecular diagnostic test that circumvents difficult DNA extractions (it is directly on blood), requires simple equipment (mini PCR machine), runs on solar power, and has a simple dipstick readout system. In the current project, we want to explore how well these new tests can detect malaria parasites in blood compared to currently available systems. The work is done in 5 African countries (Sudan, Ethiopia, Burkina Faso, Kenya, and Namibia) that all face problems with malaria diagnosis.
Who can participate?
Persons living in the catchment areas of the health centres of the participating study institutes with the suspicion of malaria (male/female, all ages) can participate in the study.
What does the study involve?
Persons who participate in the study are suspected of having malaria and attend a health facility. In addition to blood samples that will be taken from them in the context of routine diagnosis, we will take an additional small blood sample for experimental testing. Furthermore, we will take some additional clinical and demographic data. The outcome of experimental testing will not be used for the clinical management of study cases. The patients will be treated and managed according to the national health guidelines for malaria.
What are the possible benefits and risks of participating?
Cases will not have to pay the service fee for their clinic visit during this study. This study will help us to learn how the new diagnostic test will work best in patients. This may help to provide (potential) malaria patients with a better diagnosis in the future.
The risks to the safety of participants in the study is negligible as we will not provide any experimental drug. In addition, our new test will not influence the care the doctor will provide to cases and treatment will be based on the results of the health facility’s usual tests. The only risk we see could be that related to the blood collection. Indeed, the risks of drawing blood from a finger prick include temporary discomfort from the needle stick, bruising, skin infection, and fainting. However, the amount of blood collected is too small to affect participants’’, and any discomfort will rapidly go away.
Where is the study run from?
Academic Medical Center (Netherlands)
When is the study starting and how long is it expected to run for?
March 2019 to November 2024
Who is funding the study?
European and Developing Countries Clinical Trials Partnership
Who is the main contact?
Dr Henk Schallig, h.d.schallig@amsterdamumc.nl
Contact information
Principal Investigator
Amsterdam University Medical Centers
Academic Medical Center at the University of Amsterdam
Department of Medical Microbiology and Infection Prevention
Laboratory for Experimental Parasitology
Amsterdam
1105AZ
Netherlands
 ORCID ID |
0000-0002-7096-6279 |
|---|---|
| Phone | +31 646285524 |
| h.d.schallig@amsterdamumc.nl |
Study information
| Study design | Phase 3 diagnostic trial |
|---|---|
| Primary study design | Observational |
| Secondary study design | Phase 3 diagnostic trial |
| Study setting(s) | Other |
| Study type | Diagnostic |
| Participant information sheet | See additional files |
| Scientific title | Phase 3 evaluation of an innovative simple molecular test for the diagnosis of malaria in different endemic and health settings in sub-Saharan Africa |
| Study acronym | DIAGMAL |
| Study objectives | The diagnostic performance of the mini-dbPCR-NALFIA test for malaria (investigational product) has a better diagnostic performance than current diagnsotic practises in place in the particpating study sites |
| Ethics approval(s) | 1. Approved 07/04/2021, Ethics committee of the University of Gezira, Faculty of Medicine (P.O. Box 20 Wad Medani, Sudan; +249912320250; saeedosman82@yahoo.com), ref: n/a 2. Approved 10/03/2021, National ethical committee for research (03 BP7009 Ouagadougou, Burkina Faso; +226 25 33 35 94; kouetafla@yahoo.com), ref: 2021-03-057 3. Approved 01/04/2021, Institutional ethical committee in health sciences (Comité d'Ethique Institutionnel pour la Recherche en Science de la Santé, Centre National de la Recherche Scientifique et Technologique, Direction Régionale Ouest, 01 BP 545 Bobo-Dioualsso 01, Burkina Faso; +226 20981880; rouama_noelw@yahoo.fr), ref: N/Réf. A02-2021/CEIRES 4. Approved 30/06/2021, Department research ethics review committee (DRERC) of the department of microbiology, Immunology and Parasitology (DMIP) (Addis Ababa University, Addis Ababa, Ethiopia; no telephone number provided; abelishasweet@yahoo.com), ref: DRDRC/04/2021 5. Approved 25/11/2021, Ministry of Education (National Ethics Review Committee; Ministry of Education, Addis Ababa, Ethiopia; no telephone number provided; daniel.tadesse@ethernet.edu.et ), ref: 7/1-61/m259/35 6. Approved 07/09/2021, Institutional Review Board of the Addis Ababa University, College of Health Science (Addis Ababa, Ethiopia; no telephone number provided; adamuaddissie@gmail.com), ref: 07/2021 7. Approved 01/07/2021, Amref Ethics and Scientific Review Committee (P.O. Box 30125, 00100 Nairobi, Kenya; +254.20.6994000; esrc.kenya@amref.org), ref: AMREF – ESRC P991/2021 8. Approved 12/04/2021, Ministry of Health and Social Services (Harvey Street Private Bag, 13198 Windhoek, Namibia; +264.61.203.2507; Shipanga@mhss.gov.na), ref: 17/3/3/DRM |
| Health condition(s) or problem(s) studied | Malaria (uncomplicated Plasmodium falciparum malaria) |
| Intervention | Comparison of different diagnostic tests for malaria. Diagnostic performance will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and the results will be reported according to STARD principles. This phase 3 evaluation will be a prospective multi-centre diagnostic study on populations living in different malaria endemic settings and for which the disease status of each individual is not previously known. Study participants (all ages) will be identified during their visits at the study health facilities. Subjects (or parent or legal guardian in case of minors) suspected of having malaria will be asked to participate in the diagnostic study. Next to a blood sample collected for routine diagnosis in place for malaria, from each eligible case a blood sample (finger prick) will be collected in an sample (EDTA) tube for analysis with the test under investigation. An additional sample will be collected on filter paper for further comparison and quality control with PCR in reference laboratory. Some basic clinical and demographic data will be collected too. After sample collection the patients will be further referred to the local clinical practise in place. The result of experimental testing will not be taken into account whilst managing the patient. There will be no active follow-up of cases. The total duration of participation is estimated to be between 10 and 60 minutes. |
| Intervention type | Device |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Not applicable |
| Primary outcome measure | Diagnostic accuracy measured as sensitivity, specificity, negative and positive predictive value of index test (dbPCR-NALFIA) compared to reference (standard) tests at point of diagnostic testing (enrolment of study case) |
| Secondary outcome measures | 1. To determine the direct and indirect costs and benefits of allocating limited resources to implement the mini-dbPCR-NALFIA test for malaria compared to current diagnostic strategies in place. Descriptive outcome measured as availability of a report at the end of the trial 2. To determine potential barriers to successfully implement the new diagnostic platform within local, socio-economic and cultural contexts under routine conditions. Descriptive outcome measured as availability of a report at the end of the trial 3. To build a draft product dossier for CE marking and pre-qualification and to identify potential producers that can bring the platform to the market (exploitation objective). Effectiveness of dossier drafting is measured by the availability of a draft product dossier at the end of the trial 4. To strengthen the capacity of all five African partners in the field of diagnostic clinical trials, including Good Clinical and Laboratory Practices (GC/LP) training of research and auxiliary staff and prospective MSc/ PhD students, and to improve the research infrastructure at the trial sites. Effectiveness of capacity building is measured as number of staff trained at the end of the trial. 5. To disseminate the outcomes of the project to stakeholders, including scientific peers, diagnostic entities, policy makers and the lay public. Effectiveness of dissemination is measured as number of publications in peer reviewed journals at the end of the trial |
| Overall study start date | 19/03/2019 |
| Completion date | 30/11/2024 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | All |
| Sex | Both |
| Target number of participants | -Sudan (10% incidence): 876 study cases; -Ethiopia (10% incidence): 876 study cases; -Burkina Faso (20% incidence): 438 study cases; - Kenya (25% incidence): 351 study cases; - Namibia: prevalence is <1.5% in the near elimination study region. Therefore, we will perform a cross sectional study targeting 2,000 people in the study areas as was also done in a previous study |
| Total final enrolment | 4541 |
| Key inclusion criteria | In Sudan, Ethiopia, Burkina Faso and Kenya, the study will include patients who fulfil the following inclusion criteria: 1. Potential participant (patients with clinical suspicion of malaria) of all ages presenting at the health facility; 2. Coming from the health centre catchment area; 3. Informed consent from patient or of parents/guardians (in case of minors). In Namibia, the study will include persons who fulfil the following criteria: 1. Be a resident of one of the selected households or have slept the night before in this household. 2. Informed consent from potential participants (individually). |
| Key exclusion criteria | Not meeting the above inclusion criteria, depending on study site. |
| Date of first enrolment | 01/12/2021 |
| Date of final enrolment | 31/05/2024 |
Locations
Countries of recruitment
- Burkina Faso
- Ethiopia
- Kenya
- Namibia
- Sudan
Study participating centres
Nanoro
BP 218 Ouaga CMS 11
Burkina Faso
Wad Medani
01
Sudan
Nairobi
01
Kenya
Addis Ababa
01
Ethiopia
Windhoek
01
Namibia
Sponsor information
Hospital/treatment centre
Meibergdreef 9
Amsterdam
1105AZ
Netherlands
| Phone | +31.20.5665454 |
|---|---|
| p.f.mens@amsterdamumc.nl | |
| Website | https://www.amc.nl |
"ROR" |
https://ror.org/03t4gr691 |
Funders
Funder type
Government
Private sector organisation / International organizations
- Alternative name(s)
- Le partenariat Europe-Pays en développement pour les essais cliniques, A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, European and Developing Countries Clinical Trials, EDCTP
- Location
- Netherlands
Results and Publications
| Intention to publish date | 01/11/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Results will be published in a peer reviewed journal (preferably Open Access) after completion of the trial and data analysis |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 01/09/2022 | 02/09/2022 | Yes | No |
Editorial Notes
17/10/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/10/2023 to 31/05/2024.
2. The overall end date was changed from 31/12/2023 to 30/11/2024.
3. The intention to publish date was changed from 01/03/2024 to 01/11/2025.
4. The plain English summary was updated to reflect these changes.
23/05/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/05/2023 to 31/10/2023.
2. The overall end date was changed from 31/10/2023 to 31/12/2023.
3. The plain English summary was updated to reflect these changes.
4. The total final enrolment was added
13/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 15/12/2022 to 31/05/2023.
2. The overall trial end date was changed from 31/12/2022 to 31/10/2023.
3. The intention to publish date was changed from 01/12/2023 to 01/03/2024.
02/09/2022: Publication reference added.
26/01/2022: Trial's existence confirmed by Amref.
