Within the largest trial of its sort, sufferers receiving oral versus intravenous (IV) antibiotics for fracture-related infections (FRIs) had related reoperation and reinfection charges, US researchers reported this week in JAMA Surgical procedure.
However the major and secondary analyses of trial outcomes got here to completely different conclusions concerning noninferiority, leaving some uncertainty in regards to the findings.
The POvIV trial, led by investigators with the Main Extremity Trauma Analysis Consortium, was a potential, multicenter randomized scientific trial carried out at 24 US trauma facilities from March 2013 by means of September 2018. Contributors have been adults who had developed an FRI following fracture restore or arthrodesis with fixation with implants (fusion of two or extra bones utilizing screws or plates).
FRIs are widespread following fracture restore and might lengthen restoration and result in adversarial occasions. Present pointers advocate 6 weeks of IV antibiotics. However there are considerations about elevated prices and dangers related to extended IV remedy, and observational research have indicated oral antibiotics might have related efficacy. The primary purpose of the trial was to see how FRI sufferers handled with oral antibiotics for six weeks fared in contrast with those that obtained IV antibiotics.
The first final result was the variety of studied injury-related surgical interventions inside 1 yr after discharge from the preliminary an infection hospitalization. Oral antibiotics have been thought of noninferior to IV if the imply distinction in surgical interventions was lower than or equal to 0.67. Secondary outcomes included recurrence of deep surgical an infection. Outcomes have been analyzed utilizing a modified intention-to-treat (mITT) method.
Analyses differ on noninferiority
A complete of 233 sufferers (imply age, 46; 77% male) have been randomized, with 115 within the oral group and 118 within the IV group. Sufferers within the oral group had 137 surgical interventions inside 1 yr of discharge, in contrast with 118 within the IV group. The imply variety of surgical interventions inside 1 yr was 1.32 (95% confidence interval [CI]1.00 to 1.66) and 1.09 (95% CI, 0.83 to 1.36) for the oral and IV teams, respectively, with an estimated distinction of 0.23.
The higher certain of the 95% CI of the imply distinction within the unadjusted mITT evaluation was 0.59, which was decrease than the prespecified noninferiority margin of 0.67, indicating noninferiority of oral to IV antibiotics. An adjusted mITT evaluation additionally confirmed noninferiority.
However in a secondary per-protocol (PP) evaluation, the imply variety of surgical interventions inside 1 yr was 1.39 (95% CI, 1.05 to 1.74) for the oral group and 1.03 (95% CI, 0.78 to 1.30) for the IV group. The estimated distinction in means was 0.35, and the higher certain of the 95% 1-sided CI was 0.71, indicating inadequate proof to conclude noninferiority.
The therapy results estimates for the important thing secondary final result of reinfection confirmed the same sample as these for the first final result, with related charges of reinfection in each teams within the unadjusted mITT evaluation and higher variations in charges within the adjusted mITT and PP analyses.
“Regardless of assembly the noninferiority margin based mostly on mITT analyses of the first final result, the secondary PP evaluation advised fewer total examine damage–associated surgical interventions for any IV vs oral antibiotics solely teams,” the examine authors wrote.
The authors say that an vital subsequent step can be to check the outcomes of the POvIV trial to these amongst subgroups of sufferers with FRIs in a earlier trial involving sufferers with bone and joint infections. That trial (the 2019 OVIVA trial) discovered that oral antibiotics have been noninferior to IV when used in the course of the first 6 weeks of therapy, however outcomes from the subgroup evaluation haven’t been reported.
Within the meantime, the authors concluded, “Clinicians and sufferers can use these information to tell shared decision-making concerning antibiotic take care of FRIs.”
