Development of a Rapid Diagnostic Test to Identify Crimean-Congo Hemorrhagic Fever - Research and Development Testing (DETECT-R&D)

March 19, 2025 updated by: Liverpool School of Tropical Medicine

Development of a Rapid Diagnostic Test to Identify Crimean-Congo Haemorrhagic Fever At the Point-of-Care - Research and Development Testing

Background Crimean-Congo Haemorrhagic Fever (CCHF) is a rare disease with a death rate between 10% and 50%, rising to 80% during outbreaks. There are no approved drugs or vaccines, and existing treatments only work if given early. Current diagnosis is slow (2-5 days), delaying treatment, increasing risks, and heightening the chance of other people being infected. The WHO has prioritized developing rapid diagnostic tests (RDTs) to address these issues.

In regions like Afghanistan and Pakistan, delayed diagnosis is especially dangerous, particularly for pregnant women who cannot access emergency care until results are available. To tackle this, the Liverpool School of Tropical Medicine (LSTM) and Global Access Diagnostics (GADx) have created an RDT prototype to detect CCHF viral antigens. Initial testing in Türkiye (2024) showed promising accuracy, meeting WHO's basic standards but further testing is needed to confirm its reliability, especially with fresh samples.

Aims This study will evaluate the RDT using 200 fresh blood and serum samples during the 2025 CCHF season in Türkiye (Sivas and Samsun). If the test meets WHO standards, a clinical trial with 492 patients in CCHF-endemic areas of Türkiye will follow in 2026 to support regulatory approval (CE IVDR and UKCA certification).

Methods Researchers will test 200 fresh samples for diagnostic accuracy and evaluate the impact of storage conditions. This study aims to improve the test's accuracy and stability. Success will advance the development of a fast, reliable diagnostic tool for better CCHF detection and patient care in affected regions.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Background Crimean-Congo Haemorrhagic Fever (CCHF) is a life-threatening disease with a fatality rate ranging from 10% to 50%, and up to 80% in outbreaks. Despite its severity, there are no licensed drugs or vaccines available, and treatment options like Ribavirin are only effective if administered early. The current diagnostic method is slow, taking 2-5 days, which delays treatment, worsens patient outcomes, increases the risk of human-to-human transmission, and strains healthcare resources. Rapid diagnostic tests (RDTs) have been identified as a priority by the WHO to address these challenges.

Delays in diagnosis are particularly critical in regions such as Afghanistan and Pakistan, where suspected CCHF cases, especially among pregnant women, struggle to access emergency care until test results are available. The WHO R&D Blueprint has emphasized the urgent need for point-of-care (POC) tests to reduce diagnosis time and improve patient management.

To meet this need, the Liverpool School of Tropical Medicine (LSTM) and Global Access Diagnostics (GADx) have developed an RDT prototype capable of detecting CCHF viral antigens. This prototype has demonstrated promising sensitivity and specificity, exceeding the WHO's target product profile (TPP) minimum requirements of >80% sensitivity and >90% specificity, with optimal performance defined as >90% sensitivity and >95% specificity. Initial tests in Türkiye in August 2024 showed the prototype achieving sensitivity of 81.2% in 38 prospective samples and 86.4% in 117 retrospective inactivated serum samples, with specificity between 95.5% and 98%.

Further testing in December 2024 with 770 frozen stored samples in Iraq and Türkiye yielded slightly lower performance, potentially due to the effects of freezing and thawing on sample integrity. We hypothesize that freezing alters gene expression, protein stability, and aggregation, impacting test accuracy. Therefore, additional testing with fresh, unfrozen samples is needed to confirm the RDT's reliability before progressing to clinical evaluation.

Aims This study aims to evaluate the RDT using 200 fresh samples collected during the 2025 CCHF season in Sivas and Samsun, Türkiye. If performance aligns with WHO TPP standards, a clinical trial involving 492 patients in CCHF-endemic regions of Türkiye is planned for 2026. The trial data will support regulatory submissions for CE IVDR and UKCA certification.

Methods Before launching the clinical trial, the investigators will conduct further diagnostic accuracy testing on 200 fresh samples (whole blood and serum) to ensure compliance with WHO TPP standards. These samples, pseudonymized and not used for patient management, will also undergo stability testing to assess the impact of storage conditions, including refrigeration for 72 hours (at Sivas site only) and freeze-thaw cycles.

By using optimized RDTs and fresh samples, we aim to improve sensitivity and specificity beyond previous results from December 2024. This study is critical for refining the test, ensuring its effectiveness, and providing essential data on device stability. Ultimately, this research will pave the way for a reliable, rapid diagnostic tool that can significantly enhance CCHF detection and patient outcomes in endemic regions.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Turkey
      • Samsun, Turkey, 55200
        • Ondokuz Mayis University (OMU) Faculty of Medicine, Department of Clinical Microbiology and Infectious Diseases, Samsun
        • Contact:
      • Sivas, Turkey, 58000
        • Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Sivas Cumhuriyet University, Sivas
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants suspected of CCHF infection requiring a standard of care test.

Description

Inclusion Criteria:

  1. Willing to give whole blood samples (in a serum tube and EDTA tube) suspected of CCHF from Türkiye, Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Sivas Cumhuriyet University, Sivas or the department of Infectious Diseases or Ondokuz Mayis University (OMU) Faculty of Medicine, Department of Clinical Microbiology and Infectious Diseases, Samsun, that have not been frozen or refrigerated.
  2. Adults aged 18 or over.

Exclusion Criteria:

None

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
All participants
All participants will suspected of CCHF infection who present at two hospital sites in Türkiye.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Accuracy of the RDT
Time Frame: RDT will be performed at the point-of-care and RT-PCR performed 5-7 days after blood draw.
The principal objective of this study is to evaluate the diagnostic accuracy (novel RDT against RT-PCR) of the RDT using well-characterised fresh whole blood and serum samples from 200 CCHF suspected patients at the point of care.
RDT will be performed at the point-of-care and RT-PCR performed 5-7 days after blood draw.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sequencing of positive RT-PCR samples
Time Frame: This will be performed near to the end of the study at LSTM in a batch.
To sequence using MinION (Oxford Nanopore Technologies) for all RT-PCR positive (in at least one of the 3 PCRs selected) below a Ct count of 30. This objective aims to evaluate the sensitivity of the RDT in different CCHF strains.
This will be performed near to the end of the study at LSTM in a batch.
Survival status of participants
Time Frame: From enrolment to outcome of participant (discharge or death) up to 1 month post presentation
To obtain survival data on those infected with CCHF, to evaluate the use of the RDT on severe cases.
From enrolment to outcome of participant (discharge or death) up to 1 month post presentation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liverpool School of Tropical Medicine

Collaborators

Ondokuz Mayıs University
Cumhuriyet University

Investigators

  • Principal Investigator: Ana Cubas Isabel Atienzar, PhD, Liverpool School of Tropical Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2025

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

November 1, 2025

Study Registration Dates

First Submitted

March 12, 2025

First Submitted That Met QC Criteria

March 19, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 19, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LSTM 25-017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This data will be used in conjunction with next years trial for IVDR submission.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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