Randomized, non-inferiority trial comparing a nitric oxide releasing solution with a macrolide antibiotic for control of bovine respiratory disease in beef feedlot calves at high-risk of developing respiratory tract disease

•A nitric oxide releasing solution (NORS) has been developed for control of bovine respiratory disease (BRD).•Nasal administration of NORS was compared to parenteral injection of tilmicosin for BRD control in high-risk feedlot cattle.•36% and 19% of cattle were diagnosed with BRD during the 40 d following administration of NORS and tilmicosin, respectively.•An inferiority of NORS compared to tilmicosin was concluded.•NORS efficacy should be improved before it can be recommended to prevent BRD in high-risk cattle.

Nitric oxide, a molecule produced in most mammalian cells, has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as non-inferior to a parenteral injection of a macrolide antibiotic, tilmicosin, for control of bovine respiratory disease (BRD) in cattle at low-to-moderate risk of developing BRD. The objective of this study was to evaluate whether NORS was non-inferior to tilmicosin for control of BRD in cattle at high-risk of developing BRD (the target population for many BRD control programs). High-risk Angus-cross heifers (n = 840) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for BRD control. Non-inferiority was assessed by calculating the difference in prevalence of heifers diagnosed with BRD during the first 40 d after arrival between NORS and tilmicosin treatment groups. The non-inferiority margin (δ) was set at 8.5%. Thirty-six and 19% of heifers were diagnosed with BRD in the NORS and tilmicosin groups, respectively. Because the lower bound of the 2-sided 95% confidence interval (CI) of the difference in BRD prevalence between the 2 treatment groups (17%; 95% CI = 11-23%) was higher than δ, an inferiority of NORS was concluded. Although on-arrival nasal administration of NORS can be viewed as a more rational control strategy than parental injection of antibiotics, further research is needed to improve NORS efficacy before it can be recommended to prevent BRD in high-risk cattle.