The OVIVA trial: Oral versus intravenous antibiotics for bone and joint infection [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. This randomized, controlled trial found that oral antibiotics were noninferior to intravenous antibiotics for treatment failure at 1 year when started within 6 weeks of complex orthopedic infections.

2. There was no significant difference in the rate of major adverse events between the two groups.

Original Date of Publication: February 1991

Study Rundown: The Oral Versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial was a multicenter, randomized controlled trial assessing noninferiority for risk of treatment failure at 1 year for oral versus intravenous antibiotics. Overall, oral antibiotics were shown to be noninferior to intravenous antibiotics when initiated within 6 weeks of surgery (risk difference = -1.4). Likewise, there were no significant differences in the percentage of participants with at least one serious adverse event (p = 0.58). Notably, median hospital stay was significantly longer in the intravenous (14 days) versus oral (11 days) groups (p < 0.001). Based on these results, the authors support the use of oral antibiotics in the early treatment of complex orthopedic infections, however they acknowledge this may not be appropriate for all patient groups. Some strengths of this trial were its diverse patient population, with good generalizability, and high trial retention. Limitations, however, included its open-label nature. The trial did not actually assess or compare specific antibiotic agents versus others, relying on local expertise to decide. Finally, given that the trial’s selection criteria were so inclusive and heterogenous, this makes drawing more nuanced conclusions about its population difficult.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: The OVIVA trial was conducted at 26 sites in the United Kingdom, including a per-protocol analysis of 909 participants with complex bone or joint infections. The majority (60.6%) were treated with surgical intervention, and antibiotic treatment was initiated within 6 weeks of presentation in all cases. The difference in the risk of treatment failure between oral and intravenous antibiotics at 1 year was -1.4 percentage points, meeting the prespecified noninferiority criteria. The number of participants experiencing at least one serious adverse event did not differ between groups, and adverse events were most commonly related to operative site or antibiotic-related. Episodes of C. difficile diarrhea also did not significantly differ between groups. Median hospital stay was significantly longer for the intravenous group (14 days) versus the oral group (11 days) (p < 0.001). Patient-reported outcome measures did not significantly differ.

Li H-K, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. New England Journal of Medicine. 2019 Jan 31;380(5):425–36.

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