Oral versus intravenous antibiotic treatment for bone and joint infections (OVIVA): study protocol for a randomised controlled trial

Abstract

BackgroundBone and joint infection in adults arises most commonly as a complication of joint replacement surgery, fracture fixation and diabetic foot infection. The associated morbidity can be devastating to patients and costs the National Health Service an estimated £20,000 to £40,000 per patient.Current standard of care in most UK centres includes a prolonged course (4–6 weeks) of intravenous antibiotics supported, if available, by an outpatient parenteral antibiotic therapy service. Intravenous therapy carries with it substantial risks and inconvenience to patients, and the antibiotic-related costs are approximately ten times that of oral therapy. Despite this, there is no evidence to suggest that oral therapy results in inferior outcomes.We hypothesise that, by selecting oral agents with high bioavailability, good tissue penetration and activity against the known or likely pathogens, key outcomes in patients managed primarily with oral therapy are non-inferior to those in patients treated by intravenous therapy.MethodsThe OVIVA trial is a parallel group, randomised (1:1), un-blinded, non-inferiority trial conducted in thirty hospitals across the UK. Eligible participants are adults (>18 years) with a clinical syndrome consistent with a bone, joint or metalware-associated infection who have received ≤7 days of intravenous antibiotic therapy from the date of definitive surgery (or the start of planned curative therapy in patients treated without surgical intervention). Participants are randomised to receive either oral or intravenous antibiotics, selected by a specialist infection physician, for the first 6 weeks of therapy. The primary outcome measure is definite treatment failure within one year of randomisation, as assessed by a blinded endpoint committee, according to pre-defined microbiological, histological and clinical criteria. Enrolling 1,050 subjects will provide 90 % power to demonstrate non-inferiority, defined as less than 7.5 % absolute increase in treatment failure rate in patients randomised to oral therapy as compared to intravenous therapy (one-sided alpha of 0.05).DiscussionIf our results demonstrate non-inferiority of orally administered antibiotic therapy, this trial is likely to facilitate a dramatically improved patient experience and alleviate a substantial financial burden on healthcare services.Trial registrationISRCTN91566927 - 14/02/2013Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1098-y) contains supplementary material, which is available to authorized users.

Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections

“…Bone and joint infections, particularly when the implant is not removed, require at least 6 to 12 weeks of antibiotic treatment according to the majority of current guidelines. A recent unblinded and randomized trial (OVIVA) confirmed that oral antibiotic treatment is as effective as intravenous administration in bone, joint, or metalware-associated infections (17). The better results with oral antibiotics have been demonstrated with levofloxacin plus rifampin; however, other oral alternatives combined with rifampin have been associated with lower remission rates (8,11), in part due to a worse safety profile but also to a reduction in the serum concentration of companion drugs like clindamycin, co-trimoxazole, linezolid, or fusidic acid (18)(19)(20)(21), in contrast to what has been shown with fluoroquinolones (10).…”

Diagnosis and Management of Diabetic Foot Infections

“…Secondary outcomes included possible and probable treatment failure, serious adverse events, IV catheter complications, Clostridium difficile infections, early termination of randomized therapy, and resource utilization. The full methodological details are available in the published protocol (60).…”

Diabetic foot infection: Antibiotic therapy and good practice recommendations

“…Studies are underway to assess whether the strategy of using oral therapy (usually utilising oral bio‐available agents with appropriate spectrum of activity and good bone penetration) is non‐inferior to traditional IV therapy in bone and joint infection (including diabetes‐associated osteomyelitis) . A published Cochrane review of a small number of appropriate studies has suggested equipoise, except in patients with septicaemia.…”