Results from multi-country trials presented at The Union World Conference on Lung Health offer new insights into the safety, tolerability, and adherence of WHO-recommended treatment regimens for multidrug-resistant tuberculosis (MDR-TB) in children and adults.
The studies underscore both progress and challenges in managing MDR-TB, particularly in vulnerable populations such as children.
Key Findings from TBCHAMP Trial
The TBCHAMP trial, a Phase 3 double-blind, multi-site randomized study conducted in South Africa by University College London (UCL) and Stellenbosch University, evaluated Levofloxacin as a preventative treatment for MDR-TB in children and adolescents aged 0–17.
Among 818 children who received adherence support, only 7% demonstrated poor adherence, while 17% of the total cohort discontinued treatment prematurely, with reasons split between clinical (70 cases) and non-clinical (85 cases) factors.
“Adherence to Levofloxacin was generally good, but challenges remain,” researchers noted, emphasizing the need for strategies such as caregiver counseling to enhance adherence and prevent treatment interruptions.
When combined with data from the VQUIN trial, an independent Phase 3 study primarily enrolling adults in Vietnam, researchers found no significant safety concerns for Levofloxacin as a preventative treatment. However, low-grade adverse events affected tolerability and were a key reason for discontinuation, particularly among adult participants.
CATALYST Trial Raises Concerns Over Combination Regimens
Stellenbosch University researchers also presented results from the CATALYST trial, a multi-country study investigating child-friendly formulations of Clofazimine (CFZ) and Moxifloxacin (MFX), including combination regimens with Bedaquiline (BDQ). These drugs are key components of WHO-recommended regimens for rifampicin-resistant TB (RR-TB).
The study revealed that children taking the MFX, CFZ, and BDQ combination showed higher mean QTcF—a measure of the heart’s electrical activity during its resting phase—on electrocardiograms (ECG). These findings led to increased clinical visits and drug substitutions.
Researchers concluded that the MFX, CFZ, and BDQ combination should be avoided when alternatives are available, and that close ECG monitoring is critical for patients on this regimen.
Expert Perspectives and Implications for Global Health
Dr. Cassandra Kelly-Cirino, Executive Director of The International Union Against Tuberculosis and Lung Disease (The Union), highlighted the significance of these findings.
“Multidrug resistance in TB represents a severe threat, both to those living with the disease and to global health. Treatment regimens that prioritize safety and adherence are essential in combating this threat,” said Dr. Kelly-Cirino. “The new research presented at The Union Conference this week marks crucial progress, particularly in regimens designed for children.”
These findings reinforce the importance of optimizing MDR-TB treatment regimens to balance efficacy, safety, and adherence. As MDR-TB remains a pressing global health challenge, studies like TBCHAMP, VQUIN, and CATALYST contribute valuable data to guide clinical practice and policy decisions.
Further research and innovations in treatment delivery are needed to address the complexities of MDR-TB, especially for the most vulnerable populations.