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An “interview” inspired by publication of a landmark clinical trial.<\/a> All responses written by me — but be assured, they are based on reading the paper, the accompanying editorial<\/a>, the supplemental appendix, hundreds of comments on Twitter (some of them\u00a0from the study investigators)<\/a>, and even a few generous comments from the the senior author in response to email queries.<\/em><\/p>\n Me:<\/strong>\u00a0 Thank you for joining us today, and welcome to the official world of published medical literature. We’ve been waiting quite a while<\/a> with eager anticipation. Can you start out by introducing yourself?<\/p>\n OVIVA:<\/strong>\u00a0 Sure, thanks for having me. My name is OVIVA, which stands for “Oral vs. Intravenous Antibiotics” for bone and joint infections. Clever, eh?<\/p>\n Me:<\/strong> Yes, pretty good — though these makers of this “maple water”<\/a> might object. Tell me a little about yourself.<\/p>\n OVIVA:<\/strong> Well, as you know, it’s a longstanding view that adults with bone and joint infections need prolonged IV therapy for optimal treatment. But this is inconvenient, expensive, and doesn’t make a whole lot of sense since many antibiotics are well-absorbed when taken orally. Plus, the pediatricians have treated osteomyelitis with oral therapy successfully for years. So we set out to challenge this assumption that you need to use IV.<\/p>\n Me:<\/strong>\u00a0 Great idea! Where was it done, and who did it include?<\/p>\n OVIVA:<\/strong> We did it at 26 sites in Great Britain, from\u00a02010 to 2015 — solidly pre-Brexit — and enrolled around 1000 people. Eligible participants had a bone or joint infection, and would normally be treated with at least 6 weeks of intravenous antibiotics. We included people who had surgery (such as removal of an infected joint or hardware, or debridement), and those who didn’t. The treating physicians chose the antibiotics based on cultures and their clinical practice. These are deliberately very broad inclusion criteria — we wanted to make it as representative of the “real world” as possible.<\/p>\n Me:<\/strong>\u00a0 Interesting choice — really drives home the “pragmatic strategy” in clinical trials design. Any notable exclusions?<\/p>\n OVIVA:<\/strong>\u00a0 We excluded people with Staph aureus<\/em> bacteremia or endocarditis, since at that time, oral therapy would not have been standard of care — this was way before POET.<\/a>\u00a0And since we had to consider the possibility that half the participants would get IV therapy, we did not want to include anyone for whom this treatment might not be completed — hence few (if any) participants were enrolled with active injection drug use.\u00a0<\/a>[It’s not clear if anyone who uses injection drugs is in the study.]<\/em><\/p>\n Me:<\/strong>\u00a0 So what did you find?<\/p>\n OVIVA:<\/strong>\u00a0 Here’s the big news:\u00a0 Oral therapy was clearly non-inferior to IV.<\/em> Definitive treatment failure at 1 year occurred in 13% of the oral group and 15% of the IV group. These results held up in several sensitivity analyses, including something we called a “worst case” outcome. In this approach, we take the participants with missing data, and assume all these participants who were randomly assigned to receive oral therapy and no participants who were randomly assigned to receive intravenous therapy had definitive treatment failure. This introduced the worst possible bias against the oral strategy — and it was still non-inferior. Here, take a look at this figure:<\/a><\/p>\n Me:<\/strong>\u00a0 Very reassuring that the point estimates for your baseline analyses all numerically favored oral therapy. And clever job with that “worst case” scenario — good one for the doubters.<\/p>\n OVIVA:<\/strong>\u00a0 Thanks. I should mention that we were worried that the oral group would receive much longer total treatment, but this wasn’t the case — the median duration of therapy was 78 days in the intravenous group and 71 days in the oral group. Plus, even though there was more adjunctive rifampin use in the oral group, outcomes didn’t vary significantly whether this strategy was chosen.<\/p>\n Me:<\/strong>\u00a0 Any other results you’d like to highlight?<\/p>\n OVIVA:<\/strong>\u00a0 Another plus — those getting oral therapy had shorter hospitalizations and fewer complications (in particular, line-related complications). This approach to treatment of osteomyelitis will save plenty of pounds\/euros\/dollars\/etc. So oral therapy can save money, be safer, and be just as effective. Is that what you Yanks would call a home run? Or a touchdown?<\/p>\n Me:<\/strong>\u00a0 Vastly prefer the former, thank you. And no doubt these are great results — congratulations for being such a challenging, important, and rigorously conducted study. Highly likely to change clinical practice!<\/p>\n OVIVA<\/strong> (beaming)<\/em>:\u00a0 Aw shucks — that’s very kind of you.<\/p>\n![\"\"](\"https:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2019\/02\/Screen-Shot-2019-02-02-at-7.32.28-AM.png\")
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