{"id":35916,"date":"2019-03-28T09:37:24","date_gmt":"2019-03-28T09:37:24","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=35916"},"modified":"2019-03-29T13:37:41","modified_gmt":"2019-03-29T13:37:41","slug":"bedaquiline-and-delamanid-safe-when-given-together-to-treat-drug-resistant-tb","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/35916","title":{"rendered":"Bedaquiline and delamanid safe when given together to treat drug resistant TB"},"content":{"rendered":"

\"\"Polly Clayden, HIV i-Base<\/strong><\/p>\n

QT interval prolongation effects of bedaquiline (BDQ) and delamanid (DLM) given together were no more than additive in a study looking at cardiac safety of the combined use of these drugs in people with multidrug resistant (MDR)-TB.<\/strong><\/p>\n

Data from the ACTG A5343 (DELIBERATE) trial were presented at CROI 2019.<\/p>\n

BDQ and DLM are the first drugs from two new classes approved for TB in over 40 years. Both are recommended by WHO for treatment of MDR-TB by WHO.<\/p>\n

Both drugs\u2019 metabolites prolong \u2028the QT interval. Peak QT effects are at 16\u201318 weeks for BDQ and 8 weeks for DLM. The cardiac safety of these drugs given together as part of a regimen to treat MDR-TB has not been previously studied.<\/p>\n

DELIBERATE was a phase 2, randomised, open-label, three arm pharmacokinetic and safety trial. Adults with MDR-TB, receiving multidrug background treatment (MBT), were randomised 1:1:1 to receive BDQ, DLM or both (BDQ + DLM) for 24 weeks.<\/p>\n

The primary objective was to compare mean change from baseline in QTcF (in ms; averaged over weeks 8\u201324) when BDQ and DLM are given together to the mean change when each drug is given alone.<\/p>\n

People with QTcF >450 ms or CD4 count <100 cells\/mm3<\/sup> were excluded. Clofazamine was not permitted and moxifloxacin was switched to levofloxacin. HIV positive participants received dolutegravir-based ART.<\/p>\n

Three electrocardiograms (ECG) were performed at baseline, every two weeks for 24 weeks, then week 28.<\/p>\n

A core laboratory blinded to treatment arm calculated QTcF. The study defined grade 3 QTcF prolongation as >500ms or >480 ms with increase from baseline >60 ms. Grade 4 was life-threatening dysrhythmia.<\/p>\n

Sites were in South Africa and Peru. Gary Maartens\u00a0from the University of Cape Town presented these findings on behalf of the DELIBERATE investigators.<\/p>\n

Eighty-four participants were enrolled. Most (75%) were men, median age was 35 years and 37% were HIV positive.<\/p>\n

Mean baseline QTcF and standard deviations in the BDQ, DLM and BDQ + DLM arms were respectively: 398 (24), 404 (19) and 391 (14).<\/p>\n

Of 74 participants with QTc data, mean change in QTcF from baseline in the respective arms was: 11.9 (95% CI 7.4 to 16.5), 8.6 (95% CI 4.0 to 13.2) and 20.7 (95% CI 16.1 to 25.4).<\/p>\n

There were no Grade 3 or 4 QT interval prolongation events.<\/p>\n

The investigators concluded that the combined effect on the QTcF interval of co-administration of BDQ and DLM is clinically modest and no more than additive.<\/p>\n

comment<\/h3>\n

The investigators also noted the caveat that this was a carefully-screened population not receiving other DR-TB drugs that have significant QT prolongation effects (clofazimine and moxifloxacin).<\/strong><\/p>\n

Reference<\/p>\n

Dooley KE et al. QT effects of bedaquiline, delamanid or both in MDR-TB patients: The Deliberate trial.\u2028CROI 2019. Seattle. 4\u20137 March 2019. Oral abstract 84LB.
\nhttp:\/\/www.croiconference.org\/sessions\/qt-effects-bedaquiline-delamanid-or-both-mdr-tb-patients-deliberate-trial<\/a> (abstract)
\nhttp:\/\/www.croiwebcasts.org\/console\/player\/41181<\/a> (webcast)<\/p>\n\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base QT interval prolongation effects of bedaquiline (BDQ) and delamanid (DLM) given together were no more than additive in a study looking at cardiac safety of the combined use of these drugs in people with multidrug resistant …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,37],"tags":[264],"class_list":["post-35916","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-tb-coinfection","tag-croi-2019"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35916","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=35916"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35916\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=35916"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=35916"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=35916"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}