OVIVA trial

N Engl J Med. 2019 Jan 31;380(5):425-43

Contributed by Dr Sowmya Sridharan, Dr Abi Manesh

Bone and joint infections typically are treated with a prolonged course (minimum of 6 weeks) of IV therapy followed by long term oral therapy. This is not based on rigorous data, rather from small studies done decades ago. OVIVA is a large RCT that explored whether oral therapy after the first one week will be as efficacious as 6 weeks parenteral therapy. The study was done in 26 sites in UK from 2010 to 2015. The study had a non inferiority margin of 7.5%. The primary outcome was treatment failure at 1 year follow up. The trial was done in a pragmatic fashion where all sorts of bone and joint infections including prosthetic joint infections were included.

Randomizing patients with an expected majority of gram-positive infections, there was no statistical difference in the rate of treatment failure between groups; IV with 14.6% compared to oral with 13.2% (95% CI -5.6 to 2.9). Probably or possible treatment failure was similar between groups along with rates of diarrhea associated with C. Diff and other adverse events. Therapy with IV antibiotics were associated with a longer hospital length of stay (14 days vs. 11 days, P < 0.001) with more early therapy discontinuation (18.9% vs. 12.8%, P = 0.006, NNH 16) and more IV catheter complications (9.4% vs. 1.0%, P < 0.001, NNH 12). The study had a small lost to follow up group (4%).

The result of the study is potentially practice changing. Concerns in this study include a higher rate of failures in both the groups and the authors have not reported on individual oral agents and their success rates. However, for most patients oral therapy could be used up front when agents with good oral bioavailability are available.