Clinical Validation of Novel Malaria Diagnostic Tools for POC Point-of-Care Testing

Malaria Clinical Trial

Official title:

Clinical Validation of Novel Malaria Diagnostic Tools for Point-of-Care Testing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06225700
• Other study ID #: MA017
• Status: Completed
• Start date: March 1, 2023
• Est. completion date: August 1, 2023

Study information

• Verified date: March 2023
• Source: Foundation for Innovative New Diagnostics, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to perform a performance evaluation of novel diagnostic tools for detecting malaria in malaria-endemic countries. At the beginning of 2022, FIND launched a call for innovation with the distinct aim to identify malaria innovations that have the potential to address the technical and operational limitations of current malaria RDTs, particularly in view of the emergence of P. falciparum parasites with hrp2/3 deletions, the need for improved tools to identify all Plasmodium species and/or the need for improved surveillance. This study will generate valuable data on the performance of these novel non-HRP2-based tests and inform FIND and developers on technical and operational assay optimization requirements for accelerated access of these tools to market.

Description:

This study aims to support product development efforts towards novel malaria diagnostics not HRP2-based by providing early-stage technology developers with valuable information on performance and basic feasibility data that can help to accelerate development. The WHO now recommends that where pfhrp2/3 gene deletions are reported (within countries or in neighboring countries), representative baseline surveys are to be conducted among suspected cases. If >5% of false negative RDT results are attributed to these deletions, a change in RDT is necessary. Plasmodium lactate dehydrogenase (pLDH), appears as a good alternative to HRP2 as it is an essential protein expressed by all human-infecting Plasmodium species. However, pLDH-based RDTs have 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. Thus, RDTs not based on HRP2 are limited; moreover, WHO prequalified ones that can detect and distinguish between Plasmodium falciparum and Plasmodium vivax are non-existent. The current malaria diagnostic landscape demands more innovation supporting and accelerating the development of new malaria diagnostic tools that that tackle these emerging issues.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 509
• Est. completion date: August 1, 2023
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

• Aged 5 years or older
• Presenting at the study site with symptoms and signs suggestive of malaria
• Freely agreeing to participate by signing an informed consent form (adults aged 18 and older and parent/legal guardian of a child) and providing assent (children aged 13-17)
• Willing to provide venous blood sample and other samples such as foot odour.

Exclusion Criteria:

• Presence of symptoms and signs of severe disease and/or central nervous system infections, as defined by WHO guidelines Participants are excluded from the foot odour collection if the following exclusion

criteria apply:

• Skin lesions on the feet
• Infected skin on the feet
• Infected toenails

Related Conditions & MeSH terms

• Diagnoses Disease
• Malaria
• RDT

Locations

Country	Name	City	State
Rwanda	Stansile	Kigali

Sponsors (2)

Lead Sponsor	Collaborator
Foundation for Innovative New Diagnostics, Switzerland	Australian Government

Country where clinical trial is conducted

Rwanda, 

References & Publications (3)

World Health Organization, 2015. Control and Elimination of Plasmodium Vivax Malaria: A Technical Brief. Geneva: WHO Press.

World Health Organization, 2018. Malaria Rapid Diagnostic Test Performance; Summary results of WHO product testing of malaria RDTs: round 1-8 (2008-2018). Geneva.

World Health Organization. "False-Negative RDT Results and P. Falciparum Histidine-Rich Protein 2/3 Gene Deletions." Global Malaria Programme, July 2019.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Performance of nPOC	Point estimates of clinical performance characteristics (sensitivity, specificity, NPV, PPV, and DOR) with 95% confidence intervals of nPOC using nPCR as reference for detecting malaria in patients with symptoms suggestive of malaria.	3 months
Secondary	Performance of LM	Point estimates of clinical performance characteristics with 95% confidence intervals (sensitivity, specificity, NPV, PPV, and DOR) of light microscopy using nPCR as reference for detecting malaria in patients with symptoms suggestive of malaria	3 months
Secondary	Performance of comparator RDT	Point estimates of clinical performance characteristics with 95% confidence intervals (sensitivity, specificity, NPV, PPV, and DOR) of the comparator tests using nPCR as reference for detecting malaria in patients with symptoms suggestive of malaria	3 months
Secondary	Comparison between nPOC [Truenat® Malaria Pv/Pf; Truenat® Malaria Pv/Pf Hi-Sens; Humasis Hs-Malaria P.f/Pan test, Hemozoin Imager] and LM	Comparison between the clinical performance of nPOC and light microscopy	3 months
Secondary	Comparison between Hemozoin Imager and comparator RDT	Comparison between the clinical performance of between the clinical performance of Hemozoin Imager and comparator rapid diagnostic test [SD Bioline Combo/ First Response].; The percentage difference between the clinical performance characteristics of nPOC and comparator RDT with 95% confidence intervals using Tango's score method.	3 months
Secondary	Comparison of Truenat Pv/Pf and Truenat Pv/Pf High-Sens	Comparison between clinical performance of Truenat® Pv/Pf and Truenat® Pv/Pf Hi-Sens.; The percentage difference between the clinical performance characteristics of Truenat® Pv/Pf and Truenat® Pv/Pf Hi-Sens with 95% confidence intervals using Tango's score method.	3 months
Secondary	Comparison between Truenat Pv/Pf and Truenat Pv/Pf High-Sens and Realstar	Comparison between the clinical performance of Truenat® Pv/Pf and Truenat® Pv/Pf Hi-Sens with that of RealStar® Malaria Screen & Type PCR Kit 1.0.; The percentage difference between the clinical performance characteristics of the Truenat® tests (Truenat® Pv/Pf and Truenat® Pv/Pf Hi-Sens) and RealStar® Malaria Screen & Type PCR Kit 1.0 with 95% confidence intervals using Tango's score method.	3 months
Secondary	Foot odour collection	The number of volatile organic compound (foot odour samples) from Plasmodium positive and negative febrile patients that have been collected.	3 months