MalariaNCT05085301
RapiGEN BIOCREDIT Malaria Ag RDTs WHO Prequalification Study
An observational study of Malaria and Diagnoses Disease, run by Foundation for Innovative New Diagnostics, Switzerland at 2 sites in 2 countries.
Trial summary
Since their introduction in the late 90's, rapid diagnostic tests (RDTs) have markedly improved our ability to control malaria; yet they have inherent limitations which include low sensitivity in Plasmodium vivax detection and inability to detect hrp2/3 gene deleted Plasmodium falciparum parasites. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Malaria, Diagnoses Disease, RDT
- What is being tested?
- Rapid diagnostic test
- How many people
- 674 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Dec 2021to 30 May 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with symptoms suggestive of malaria seeking clinical care in health facilities. All patients will be assessed for eligibility of enrollment and those who full filled the criteria will be recruited in the study after signing an informed consent.
Who may be able to join
- Aged 5 years old or older
- Presenting at the study site with fever or a history of fever during the preceding 48 hours
- Freely agreeing to participate by providing informed consent (and assent, if applicable)
Who cannot join
- Presence of symptoms and signs of severe illness and/or central nervous system infections as defined by WHO guidelines
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Clinical Performance of RapiGEN BIOCREDIT Malaria Ag RDTs for Detection of Plasmodium Infections in Patients With Symptoms Suggestive of Malaria
Since their introduction in the late 90's, rapid diagnostic tests (RDTs) have markedly improved our ability to control malaria; yet they have inherent limitations which include low sensitivity in Plasmodium vivax detection and inability to detect hrp2/3 gene deleted Plasmodium falciparum parasites. In addition, the spread of P. falciparum parasites lacking hrp2 gene jeopardizes the long-term use of P. falciparum-specific HRP2-based RDTs.
A partnership between RapiGEN, FIND, and the Bill and Melinda Gates Foundation (BMGF) is addressing these limitations by developing five novel malaria RDTs with improved pLDH and HRP2 detection.
Read more
RapiGEN has also developed three novel malaria RDTs - BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf (pLDH) - to address these drawbacks. The BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) is a combo test that detects P. falciparum and P. vivax on a single device. BIOCREDIT Malaria Ag Pf (pLDH/HRP2) targets both PfLDH and HRP2 antigens in P. falciparum; and BIOCREDIT Malaria Ag Pf (pLDH) has improved detection of pLDH in P. falciparum.
In countries with circulation of hrp2/3 deleted P. falciparum malaria parasites or high P. vivax burden, these improved RDTs may be invaluable in malaria elimination.
This study is a prospective and retrospective evaluation of RapiGEN's BIOCREDIT Malaria Ag RDTs in malaria-endemic countries to assess their clinical performance for detection of malaria. The purpose of this study is to provide a high level outline of the study design and conduct to support the collation of a data package for WHO Pre-Qualification proposed study.
Read the detailed description
Malaria continues to create a major health burden in the tropics especially in Africa. Introduction of Artemisinin-based combination therapy (ACT) has dramatically improved the outcomes of morbidity and mortality of malaria cases. Introduction of RDTs as well dramatically influenced cases detection hence treatment. The situation in Sudan is not different from the general picture in all Africa and witness great reduction of deaths from malaria since the introduction of ACT in 2005 (1). The national protocol depends now on Giemsa stained slides microcopy or certified RDTs for diagnosis and ACT as first and second line of treatment (2).
Recommendation by World Health Organization (WHO) on parasitological confirmation of malaria cases by microscopy or rapid diagnostic tests (RDTs) before treatment increased the use and availability of RDTs worldwide (3).
Rapid diagnostic tests, since their introduction in the late 90's, have dramatically improved our ability to control malaria. Most RDTs are based on histidine-rich protein 2 (PfHRP2) or lactate dehydrogenase (pLDH), which are present in Plasmodium falciparum only and all human-infecting Plasmodium species respectively (4). However, the gradual spread of hrp2/hrp3-deleted mutants in several endemic countries in South America, Asia and Africa exerts a substantial potential impact on the utility of HRP2-based RDTs for case management in these settings.
Plasmodium lactate dehydrogenase (pLDH), on the other hand, appears as a good alternative to HRP2 as it is an essential protein expressed by all human-infecting Plasmodium species; however, pLDH-based RDTs were shown to perform poorly at low parasitaemia, which is common among patients infected with P. vivax, P. malariae and P. ovale species as well as in asymptomatic infections. Therefore, it is less preferred in endemic-countries. In these settings, malaria microscopy holds its reign as the standard of reference thanks to its low direct cost and ability to detect, quantify, and differentiate malaria parasites. However, it is also labour-intensive, time-consuming and expertise-demanding.
With the aim of addressing these limitations, RapiGEN has developed novel malaria RDTs, in partnership with FIND and the Bill and Melinda Gates Foundation (BMGF). RapiGEN developed BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf.
These may provide added value compared to currently available malaria RDTs, especially in settings where current tests prove to be insufficient due to hrp2 deletion or high burden of P. vivax malaria.
- Conditions
- Malaria, Diagnoses Disease, RDT
- Being tested
- Rapid diagnostic test
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rapid diagnostic testDiagnostic test
Also called BIOCREDIT
The performance of three index tests and two comparator tests will be compared to reference tests and gold standard microscopy.
What is being measured
The primary outcome is the main question the study is designed to answer.
Point estimates of BIOCREDIT Malaria Ag Pf
Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals for BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf (pLDH) using the reference test (nPCR) as standard of truth for the detection of P. falciparum infections in patients with symptoms suggestive of malaria
Measured: 2 months
Point estimate of BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH)
Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals for BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) using the reference test as standard of truth for the detection of P. falciparum and P.vivax infections in patients with symptoms suggestive of malaria
Measured: 2 months
Secondary outcomes (2)
Point estimates of comparator tests
Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals of comparator tests using the reference test as standard of truth for the detection of P. falciparum and, P.vivax infections in patients with symptoms suggestive of malaria
Measured: 2 months
Frequencies of hrp2/3 gene deletions
Frequencies of P. falciparum infections containing HRP2 and/or HRP3 mutations and the impact of those on HRP2-based RDT diagnostic accuracy
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2021
- Study start1 Dec 2021
- Primary completion30 May 2022
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 674 participants (actual)
Sponsor and investigators
- Lead sponsor
- Foundation for Innovative New Diagnostics, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- University of Khartoum, Eijkman Institute for Molecular Biology
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05085301
- Sponsor's protocol ID
- MA016 RapiGEN
- Status last verified
- Oct 2023
- First submitted
- 7 Oct 2021
- Last updated
- 13 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Performance of RapiGEN BIOCREDIT Malaria Ag RDTs for Detection of Plasmodium Infections in Patients With Symptoms Suggestive of Malaria
- ClinicalTrials.gov ID
- NCT05085301
- Acronym / sponsor ID
- MA016 RapiGEN
- Conditions
- Malaria, Diagnoses Disease, RDT
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 674 participants (actual)
- Lead sponsor
- Foundation for Innovative New Diagnostics, SwitzerlandUniversity, hospital or other
- Collaborators
- University of Khartoum, Eijkman Institute for Molecular Biology
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 30 May 2022 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 20 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Since their introduction in the late 90's, rapid diagnostic tests (RDTs) have markedly improved our ability to control malaria; yet they have inherent limitations which include low sensitivity in Plasmodium vivax detection and inability to detect hrp2/3 gene deleted Plasmodium falciparum parasites. In addition, the spread of P. falciparum parasites lacking hrp2 gene jeopardizes the long-term use of P. falciparum-specific HRP2-based RDTs.
A partnership between RapiGEN, FIND, and the Bill and Melinda Gates Foundation (BMGF) is addressing these limitations by developing five novel malaria RDTs with improved pLDH and HRP2 detection.
RapiGEN has also developed three novel malaria RDTs - BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf (pLDH) - to address these drawbacks. The BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) is a combo test that detects P. falciparum and P. vivax on a single device. BIOCREDIT Malaria Ag Pf (pLDH/HRP2) targets both PfLDH and HRP2 antigens in P. falciparum; and BIOCREDIT Malaria Ag Pf (pLDH) has improved detection of pLDH in P. falciparum.
In countries with circulation of hrp2/3 deleted P. falciparum malaria parasites or high P. vivax burden, these improved RDTs may be invaluable in malaria elimination.
This study is a prospective and retrospective evaluation of RapiGEN's BIOCREDIT Malaria Ag RDTs in malaria-endemic countries to assess their clinical performance for detection of malaria. The purpose of this study is to provide a high level outline of the study design and conduct to support the collation of a data package for WHO Pre-Qualification proposed study.
Detailed description
Malaria continues to create a major health burden in the tropics especially in Africa. Introduction of Artemisinin-based combination therapy (ACT) has dramatically improved the outcomes of morbidity and mortality of malaria cases. Introduction of RDTs as well dramatically influenced cases detection hence treatment. The situation in Sudan is not different from the general picture in all Africa and witness great reduction of deaths from malaria since the introduction of ACT in 2005 (1). The national protocol depends now on Giemsa stained slides microcopy or certified RDTs for diagnosis and ACT as first and second line of treatment (2).
Recommendation by World Health Organization (WHO) on parasitological confirmation of malaria cases by microscopy or rapid diagnostic tests (RDTs) before treatment increased the use and availability of RDTs worldwide (3).
Rapid diagnostic tests, since their introduction in the late 90's, have dramatically improved our ability to control malaria. Most RDTs are based on histidine-rich protein 2 (PfHRP2) or lactate dehydrogenase (pLDH), which are present in Plasmodium falciparum only and all human-infecting Plasmodium species respectively (4). However, the gradual spread of hrp2/hrp3-deleted mutants in several endemic countries in South America, Asia and Africa exerts a substantial potential impact on the utility of HRP2-based RDTs for case management in these settings.
Plasmodium lactate dehydrogenase (pLDH), on the other hand, appears as a good alternative to HRP2 as it is an essential protein expressed by all human-infecting Plasmodium species; however, pLDH-based RDTs were shown to perform poorly at low parasitaemia, which is common among patients infected with P. vivax, P. malariae and P. ovale species as well as in asymptomatic infections. Therefore, it is less preferred in endemic-countries. In these settings, malaria microscopy holds its reign as the standard of reference thanks to its low direct cost and ability to detect, quantify, and differentiate malaria parasites. However, it is also labour-intensive, time-consuming and expertise-demanding.
With the aim of addressing these limitations, RapiGEN has developed novel malaria RDTs, in partnership with FIND and the Bill and Melinda Gates Foundation (BMGF). RapiGEN developed BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf.
These may provide added value compared to currently available malaria RDTs, especially in settings where current tests prove to be insufficient due to hrp2 deletion or high burden of P. vivax malaria.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with symptoms suggestive of malaria seeking clinical care in health facilities. All patients will be assessed for eligibility of enrollment and those who full filled the criteria will be recruited in the study after signing an informed consent.
Key inclusion criteria (3 listed)
- Aged 5 years old or older
- Presenting at the study site with fever or a history of fever during the preceding 48 hours
- Freely agreeing to participate by providing informed consent (and assent, if applicable)
Key exclusion criteria (1 listed)
- Presence of symptoms and signs of severe illness and/or central nervous system infections as defined by WHO guidelines
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rapid diagnostic testAlso: BIOCREDITThe performance of three index tests and two comparator tests will be compared to reference tests and gold standard microscopy. | Diagnostic test | – |
Primary outcome
Point estimates of BIOCREDIT Malaria Ag Pf
Time frame: 2 months
Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals for BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf (pLDH) using the reference test (nPCR) as standard of truth for the detection of P. falciparum infections in patients with symptoms suggestive of malaria
Point estimate of BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH)
Time frame: 2 months
Point estimates of diagnostic accuracy characteristics (sensitivity, specificity, NPV, PPV) with 95% confidence intervals for BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) using the reference test as standard of truth for the detection of P. falciparum and P.vivax infections in patients with symptoms suggestive of malaria
2 secondary outcomes
Point estimates of comparator tests
Time frame: 2 months
Frequencies of hrp2/3 gene deletions
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Malaria
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
Not yet recruitingObservational study
Factors Influencing Adoption of a Novel Malaria Treatment in Côte d'Ivoire, Ghana, and Rwanda
Malaria
RecruitingPhase 1
Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
Malaria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria and Diagnoses Disease, run by Foundation for Innovative New Diagnostics, Switzerland at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Indonesia, Sudan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Point estimates of BIOCREDIT Malaria Ag Pf (time frame: 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2023.