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Effectiveness and cardiovascular safety of delamanid-containing regimens in adults with multidrug-resistant or extensively drug-resistant tuberculosis: A nationwide cohort study from Belarus, 2016-18
- Source :
- Monaldi Archives for Chest Disease, Vol 91, Iss 1 (2021)
- Publication Year :
- 2020
-
Abstract
- To address the sub-optimal treatment outcomes among patients with multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the National TB Programme in Belarus started using new drugs such as bedaquiline and delamanid in 2015-16. In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. This was a nationwide cohort study involving analysis of routinely collected programme data from the national and six regional TB hospitals. Cardiovascular adverse events (AEs) were classified as serious or not, based on international guidelines. We conducted Cox proportional hazards regression and calculated adjusted hazards ratio(aHR) and 95% confidence intervals(CI) to evaluate factors associated with AEs and unsuccessful treatment outcomes (death, failure and lost-to-follow-up). Of 125 patients enrolled (35, 28% females; mean age 43 years), 85(68%) had XDR-TB. All the patients received delamanid and 20 patients received both delamanid and bedaquiline. Cardiovascular AEs (177 episodes in total), were observed in the majority (73%) of patients but were mild and managed easily. The most common cardiovascular AEs were QTcF prolongation (64/177, 36%) and other electrocardiography (ECG) abnormalities (40/177, 23%). There were two instances of serious AEs leading to death, both of which were not related to delamanid. In multivariable analysis, male sex (aHR 0.72; 95% CI 0.51-0.99), and baseline ECG abnormalities (aHR 1.68; 95% CI 1.19-2.36) were associated with cardiovascular AEs. Median time to culture conversion was 1.1 months (interquartile range: 1.0-2.1). Culture conversion was observed in 115 (92%) patients at six months of treatment and 110 (88%) completed the treatment successfully. Loss to follow-up, failure and death were observed in 6%, 4% and 2% patients respectively. Among those assessed at 12 months post-treatment (n=33), recurrence was seen in one patient. The only factor associated with unsuccessful treatment outcomes in multivariable analysis was baseline Hepatitis C co-infection (aHR 3.61; 95% CI 1.09-11.95). In conclusion, treatment using delamanid-containing regimens was effective and had a favourable safety profile. We hope our findings inform the development of national clinical guidelines and scale-up of new drugs in other countries.
- Subjects :
- Pulmonary and Respiratory Medicine
Adult
Male
fluoroquinolone resistance
medicine.medical_specialty
new anti-tuberculosis drugs
Tuberculosis
Republic of Belarus
Extensively Drug-Resistant Tuberculosis
Antitubercular Agents
lcsh:Medicine
Cohort Studies
Interquartile range
Internal medicine
Culture conversion
Medicine
Humans
adverse drug safety monitoring
Oxazoles
business.industry
lcsh:R
Hazard ratio
Extensively drug-resistant tuberculosis
rifampicin resistance
Hepatitis C
medicine.disease
second-line injectable drug resistance
Treatment Outcome
Nitroimidazoles
Female
Delamanid
Cardiology and Cardiovascular Medicine
business
medicine.drug
Cohort study
Subjects
Details
- ISSN :
- 11220643
- Volume :
- 91
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace
- Accession number :
- edsair.doi.dedup.....b577712fd1e9c304984102c7b8d51d73