Challenges and Implications of the V Quinn TB Prevention Trial
Gregory Fox, PhD outlines the trial's challenges, the impact of combining results with the TB Champ trial, and the role of collaboration in strengthening research outcomes.
The V Quinn trial assessed levofloxacin as a preventive treatment for drug-resistant tuberculosis (MDR-TB) in household contacts of MDR-TB patients in Vietnam. A total of 2041 participants were randomized to receive six months of daily levofloxacin or a placebo, with TB incidence as the primary endpoint.
The study found no statistically significant difference in TB rates: .6% of participants in the levofloxacin group and 1.1% in the placebo group developed TB (incidence rate ratio .55). While adverse events were more common in the levofloxacin group (31.9% vs 13%), there was no significant difference in serious adverse events, and no fluoroquinolone resistance emerged.
In the last part of our conversation with Gregory Fox, PhD, MIPH, FRACP, MBBS, BSc(Med), GAICD, described one of the main challenges of the trial: the unexpectedly low number of TB cases among the study participants. He explained, “The number of people who developed tuberculosis amongst those household contacts was quite small compared to what we had expected based upon previous literature.”
He further noted that a significant proportion of TB cases developed before the trial treatment started. “About two-thirds of people who had tuberculosis developed the TB before they actually began treatment for the trial.” This issue arose due to the long period of exposure for individuals living with MDR-TB patients. The early onset of TB among many participants reduced the opportunity to prevent new cases of the disease during the trial period.
Fox also acknowledged the difficulty of estimating the sample size accurately, which contributed to the study’s challenges. “Because there’s a lot of cases of prevalent tuberculosis, there weren’t so many cases of incident tuberculosis later on. So the main limitation was that we didn’t have as many events in the placebo group as we had expected.” He pointed out that a similar challenge was encountered in the TB Champ study, another study evaluating levofloxacin for TB prevention.
In response to this issue, Fox explained that the team had two options: either extend the trial with a substantially larger sample size, which would delay results, or combine results from both the V Quinn and TB Champ trials to increase statistical power. “We chose to combine results, which solved that problem.”
Another major challenge was the large scope of the study. “In the V Quinn study, there were over 2000 participants who had to be followed up for 30 months,” Fox said, highlighting the complexity of managing such a large trial. “Our team in Vietnam did an exceptional job… and was able to follow up more than 95% of people to the point of an endpoint.” He expressed confidence in the trial’s data accuracy, stating that the follow-up rate helped ensure that the study didn’t underestimate the number of outcomes.
Fox emphasized the importance of interpreting the results from both the V Quinn and TB Champ trials, as well as the combined meta-analysis, in drawing meaningful conclusions. “We can conclude that levofloxacin is effective in preventing tuberculosis amongst these high-risk contacts,” he stated.
He also highlighted the drug’s safety profile, “It is very well tolerated in children and adults.” Although the levofloxacin group experienced a higher rate of low-grade adverse events compared to the placebo group, there was no significant difference in the occurrence of high-grade adverse events (grade 3-4). Fox stressed that levofloxacin could be considered a safe option for this population.
Additionally, the trial did not show any difference in cardiac events between the levofloxacin and placebo groups, supporting the conclusion that cardiac monitoring is not necessary when using this treatment, “For clinicians treating patients with this drug, looking to use symptomatic treatments such as paracetamol and non-steroidal anti-inflammatory drugs might be appropriate if they are experiencing adverse events earlier in the treatment.”
Fox reflected on the success of the partnership between the V Quinn and TB Champ trials. “One of the real successes of our trial is the partnership between the V Quinn trial and the TB Champ trial,” he said, emphasizing the value of cross-country and cross-research group collaboration. “The more that we can be working together across research groups and across countries and settings, the stronger the evidence we’ll be able to generate.”
