TB-CAPT completes enrolment for the XDR-Trial in South Africa
The TB-CAPT consortium has successfully completed enrolment for the XDR trial, undertaken by clinical sites in Green Point (Cape Town) and Gqeberha (formerly Port Elizabeth), South Africa. Initial data analysis began late last year, and the interim results for the feasibility aspects of the study look promising.
In 2020, 9.9 million people fell ill with tuberculosis (TB), with 4.1 million people undiagnosed or not reported. There was also an 18 percent drop in the number of TB cases reported in 2021 compared to the year before, reflecting lower access to TB diagnostics, partly driven by the COVID-19 pandemic and limited resources. Only one-third of the 450,000 people with drug-resistant TB received were diagnosed, and less than 60 percent of those who received treatment were treated successfully. There is an urgent need for improved and more accessible diagnostics for TB and drug-resistant TB, with faster turnaround times and better linkage to care.
The TB-CAPT XDR trial is a laboratory-based feasibility study that aims at evaluating the accuracy of a new diagnostic test for drug-resistant TB (the Xpert MTB/XDR cartridge on GeneXpert) on 753 samples from patients with rifampicin-resistant TB in South Africa. The study is led by Prof Helen Cox and Dr Chad Centner from the University of Cape Town. The laboratories conducting the study at Green Point and in Gqeberha are both part of the National Health Laboratory Service (NHLS). Reaching the enrolment target on time is a big achievement, especially as the teams were forced to navigate challenges such as staff shortage and social distancing regulations due to COVID-19 during the enrolment phase.
Modified laboratory workflow
For the study, the TB-CAPT XDR trial team used residual samples that were leftover from routine testing in the two NHLS laboratories. This recruitment method enabled the team to complete enrolment much faster than if they would have collected new samples directly from patients in TB clinics or hospitals. Even though the team did not work directly with participants, patient privacy was a central component of the enrolment process. The TB-CAPT team is not able to trace any samples back to a patient.
Beyond evaluating the accuracy of the Xpert MTB/XDR cartridge on GeneXpert, the TB-CAPT XDR trial also sought to evaluate the modified laboratory workflow and assess the feasibility of using sample leftovers for further testing for research purposes.
The study procedure was designed to fit into the routine laboratory workflow and minimize interruptions to standard procedures, and while evaluation of the process is still ongoing, the initial perception from the study team is that this has worked well. The TB-CAPT team was also pleased to see that the laboratory staff was highly motivated to test the new procedure and make it successful.
Promising interim results
The TB-CAPT XDR trial team began preliminary data analysis during the enrolment phase in late 2021. They recently submitted an abstract for presentation at the next European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), which will take place in Lisbon, Portugal, in April this year. When the abstract was submitted, the group had enrolled half of the study’s target sample size and interim results showed a very strong trend of promising results in terms of operational feasibility.
One initial concern by the team was that the procedural samples that were saved from routine testing in the laboratories would not be sufficient for the MTB/XDR assay, but preliminary results show that there is sufficient remaining specimen in more than 97 percent of the cases. Another concern was related to whether setting aside samples for a certain period would reduce the detection rate of TB, but the team has found that they still had relatively good MTB detection rates when they tested these samples.
The TB-CAPT XDR trial team has also been able to demonstrate a reduction in turnaround time for TB drug resistance detection results. The MTB-XDR assay performs drug susceptibility testing for three first-line drugs. Normally, the turnaround time for this type of test is days to weeks, sometimes even months. With the new assay, the turnaround time can be reduced to just a few hours.
The diagnostic accuracy analysis will begin when the reference standard testing has been finalized this autumn.
The entire XDR trial team enjoyed the collaborative nature of the study and is excited for the MTB/XDR assay to be implemented, hoping it can be a real game-changer for diagnostics of drug-resistant TB. This study will inform national policy in South Africa and other high burden TB countries on the feasibility of implementing the Xpert MTB/XDR assay within the diagnostic algorithm. Adoption of the assay will lead to faster detection of drug-resistant TB, more rapid initiation of appropriate anti-TB treatment, and better patient outcomes.
The TB-CAPT XDR trial team at the University of Cape Town (from the left to the right): Greshan Kisten, Minkie Gumede, Helen Cox, Tania Dolby, Heibie Fielies, Lynn Atcheler, Widaad Zemanay, Chad Centner, Parveen Brown. 
The TB-CAPT XDR trial team at the University of the Witwatersrand (from the left to the right): Riffat Munir, Lucky Ngwenya, Lesley Scott, Anura David.