Abstract
<title>Abstract</title> <p> Background Although adjunctive immunomodulation has shown promise in canine leishmaniosis (CanL), evidence remains limited. We evaluated Omnifect® Proimmune (OP), a nutraceutical containing lyophilized inactive lipopolysaccharide from <italic>Ochrobactrum intermedium</italic> and antioxidants, as an adjunct to standard therapy (ST) in dogs with clinical CanL caused by <italic>Leishmania infantum</italic> . Methods In this prospective, 12-month, non-randomised, masked, placebo-controlled, parallel-group clinical study, 56 client-owned dogs with clinical CanL received conventional antileishmanial treatment plus either OP or placebo. Analyses followed an intention-to-treat approach. Longitudinal outcomes were assessed using mixed-effects models adjusted for grouped baseline LeishVet stage. Survival was evaluated using Kaplan–Meier and Cox proportional hazards models. Results Of the 56 dogs, 27 received OP + ST and 29 placebo + ST. Thirty-five completed scheduled follow-up, 16 died and five were withdrawn or did not complete the protocol. Clinical signs improved in both groups, but OP did not demonstrate overall superiority in LeishVet stage, serology, TaqMan qPCR, UPC or individual ELISA cytokine trajectories. Serum creatinine was lower in the OP group at day 180 [0.86 (0.76–1.00) vs 1.02 (0.84–1.40) mg/dl; nominal p = 0.031], but no corresponding between-group difference in UPC was detected. The pooled-serum membrane-array analysis showed its largest descriptive between-group difference in the growth/angiogenesis axis but, owing to pooling, lacked biological replication and did not permit individual-level inference (qFDR approximately 0.07). Treatment group was not independently associated with survival (placebo vs OP: hazard ratio [HR] 1.42, 95% confidence interval [CI] 0.49–4.11; p = 0.518), whereas higher baseline creatinine (HR 2.43, 95% CI 1.47–4.00; p < 0.001) was associated with a higher hazard of death/euthanasia and higher baseline albumin (HR 0.31, 95% CI 0.13–0.75; p = 0.009) with a lower hazard. Conclusions Adjunctive OP did not demonstrate overall superiority over placebo when added to ST for clinical CanL, and no safety concern attributable to OP was identified. The isolated between-group difference in serum creatinine at day 180 and the descriptive growth/angiogenesis pattern warrant further investigation but do not establish renal or immunological efficacy. </p>