Trial DesignPartial oral treatment of endocarditis
Section snippets
Background
The incidence of infective endocarditis (IE) is increasing.1 Mortality remains high—from 9% to 46%2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18—despite improvements in diagnostic tools and novel antibiotics.
Management of IE includes antibiotic therapy, diagnostic workup for identification, and treatment of a primary infective focus and, in roughly half of the cases, surgery. Treatment strategies and timing of surgery are primarily based on consensus, retrospective studies and
Study objectives
The Partial Oral Treatment of Endocarditis (POET) study is designed primarily to determine the safety and efficacy of partial oral treatment of IE compared with traditional full-length parenteral treatment. Secondary objectives are to investigate the effects of partial oral and outpatient treatment on patient-experienced quality of life and the economic consequences of this strategy.
Methods
The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents.
Timeline
Inclusion was initiated in the first center in July 2011. All centers will have begun inclusion by October 2012. The incidence of IE in Denmark is around 500 per year. The Danish National Board of Health recommends that patients with IE be referred to one of the participating heart centers. However, approximately a third of Danish patients with IE are expected to be treated outside the participating tertiary heart centers due to disability and/or severe comorbidities. Based on this, we estimate
Substudies
A number of substudies have already been planned. The electronic case report form will contain information about included and nonincluded patients and will serve as a national IE database during and after the study period. A detailed description of the pathogens including MIC values will be produced. Furthermore, studies of magnetic resonance imaging of the cerebrum and positron emission tomography–computed tomography (PET-CT) to determine the prevalence and localization of other foci of
Study organization
The study is a researcher-driven clinical trial. Researchers from Rigshospitalet and the Danish Society of Cardiology initiated the study. The protocol was written by the steering committee, with 1 cardiologist from each participating center, 1 representative from the Danish Society of Cardiology, and K. Iversen. An antibiotic group consisting of the involved clinical microbiologists and specialists in infectious diseases has been set up. This group is responsible for the recommendations for
Funding
Only minor expenses in addition to ordinary clinical expenses are expected during treatment. Participating centers will cover their own additional costs related to the study. Funding for study staff has been partly achieved by the Danish Heart Foundation and will continuously be sought from national sources. Any additional costs related to the study will be covered by the participating centers. There will be no additional costs for the patients.
Ethics
The study protocol is approved by the local ethics committees (H-R-2011-40) and the Danish Data Protection Agency (30-0598). All eligible patients will be informed about the study orally and in writing, and patients will be included only after informed consent has been obtained.
Because of very close safety monitoring by experts in the management of IE, the risks to patients included in the oral treatment arm are low. Potential gains for patients include the benefits related to earlier discharge
Status of the study
Five centers have begun inclusion, 46 patients having been included in the study to date (July 20, 2012).
One patient randomized to parenteral treatment has experienced a primary end point (unplanned cardiac surgery). One of the patients has switched from oral to parenteral therapy due to nausea.
The last center will initiate inclusion within the forthcoming 2 months.
Discussion
The POET study investigates a new treatment strategy for IE. If the hypothesis of noninferiority of partial oral treatment is confirmed, this may have a considerable impact on the future management of IE.
The main concern of this trial is the safety of partial oral treatment. However, theoretical and empirical data suggest that oral treatment is a promising strategy, and the study design ensures that treatment failure will be detected early.
Pharmacokinetic data from orally administered
Conclusion
The resource demands, complications of prolonged intravenous therapy, and psychologic effects associated with the present management of IE make it highly relevant to seek alternative and more lenient strategies. The hypothesis that oral treatment is as efficient and safe as parenteral therapy is suggested by a literature review, by pharmacokinetic considerations, and by our local experience.
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RCT reg no. NCT01375257.