Accelerated treatment of endocarditis – The POET II trial: Rationale and Design of a Randomized Controlled Trial

Abstract Background The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to six weeks for patients with left sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE and complications to long hospital stays challenge the rationale for fixed treatment durations in all patient. Objective To conduct a non-inferiority RCT (acronym POET II), investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE. Methods The POET II trial is a multicentre, multinational, open-label, non-inferiority RCT. Patients with definite left-sided IE due to Streptococcus spp., Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transoesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, while standard length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization. Conclusions The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp., Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations and clinical practice may be altered.