PARIS — Two landmark clinical trials reported recently at the Union meeting showed that an oral antibiotic taken once daily for six months substantially reduced the risk of developing drug-resistant tuberculosis (TB). The antibiotic levofloxacin safely reduced the risk of multidrug-resistant (MDR) TB in children by 56 percent, researchers from the Desmond Tutu TB Centre at Stellenbosch University recently reported.
A second study, the VQUIN Trial, was conducted primarily among adults and adolescents and found that levofloxacin reduced the risk of MDR-TB in adults and adolescents by 45 percent. Together, the two studies demonstrated that levofloxacin can stop the risk of MDR-TB among family and other household members, curtailing the global impact of this lethal pathogen.
Evidence to date has been limited about MDR-TB preventive treatment since no randomized controlled trials have ever been conducted. TB-CHAMP took place in South Africa, in six research sites in five provinces serving communities with high burdens of TB and MDR-TB, focusing mainly on children below five years of age.
“There have been many advancements in the science around preventing drug-susceptible TB, but very little rigorous data on preventing drug-resistant TB,” said Professor Anneke Hesseling, MBChB, MSc, PhD, director of the Desmond Tutu TB Centre and the overall principal investigator of the TB-CHAMP trial, at Stellenbosch University. “We have now found a way to safely protect children when an adult in the household has MDR-TB. The importance of safeguarding our children from drug-resistant disease cannot be underestimated. The benefit to children, their families, and communities may be substantial.”
The TB-CHAMP and VQUIN trials
In the TB-CHAMP trial, 453 children who had been exposed to an adult with MDR-TB in their household were given levofloxacin—only five developed MDR-TB. There were very few side events from the medicine: Specifically joint pain and tendonitis, traditionally a concern, were very uncommon in children receiving levofloxacin.
In the VQUIN trial, 2,041 adults and children living with a person with MDR-TB in the household were given six months of levofloxacin and followed up for 30 months. The study took place in 10 provinces across Vietnam. It found that there were 45 percent fewer cases of TB in the group given levofloxacin compared to the placebo group. A lower number of cases of TB occurred in the placebo group than expected. Overall, levofloxacin was found to be safe and well-tolerated in adults and children.
TB remains one of the top causes of death in children globally and is one of the top killers of children younger than five years. An estimated 30,000 children below 15 years of age develop MDR-TB disease each year, which is complex to treat with current medications that have many side effects. The cost of treatment is a burden to families and health services alike.
Fewer than 20 percent of children with MDR-TB are currently diagnosed and treated globally. This makes them one of the most neglected populations affected by TB globally. Many of these children were in close contact with an infectious MDR-TB patient and identifying these children, screening them for TB, and offering preventive treatment will be critical to find more cases and also to prevent MDR-TB in children.
Bayesian analysis of trial data
In December 2023, an advisory committee of the World Health Organization will consider new guidelines for MDR-TB preventive treatment. The data from the TB-CHAMP and the VQUIN trials is being shared to inform how these deliberations produce new recommendations for children and adolescents. The TB-CHAMP and VQUIN trials also completed work on other important considerations such as acceptability of the drug regimen, feasibility, health economics, pharmacokinetics, and antimicrobial resistance.
The teams from the TB-CHAMP and VQUIN trials collaborated before the trials were unblinded, and combined their data on efficacy and safety in traditional and novel Bayesian approaches. Jointly, they showed that across both trials, levofloxacin reduced the risk of developing TB by 60 percent. Novel Bayesian analysis showed similar results for each trial, individually.
‘This novel Bayesian analysis, combining data from trials in two trial populations using novel methodology developed at Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL), may pave the way for combining future pediatric and adult trial data, ensuring that children are not left behind. By carefully planning this work, in advance, we have been able to present these important findings alongside the main results of the two trials, with greater potential impact on global guidelines and policy,” said Trinh Duong, TB-CHAMP trial statistician and lead for the combined analyses from MRC Clinical Trials Unit at UCL.
- This press release was originally published on the Desmond Tutu TB Centre, Stellenbosch University website