Clinical trial NCT01375257: Partial Oral Treatment of Endocarditis
Official title: Partial Oral Treatment of Endocarditis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Endocarditis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2011-06-17
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background Current management of infective endocarditis include admission and treatment with parenteral antibiotics for 4 weeks - 6 weeks. Resource demands and psychological issues of present management strategy make it highly relevant to seek for alternative more lenient alternatives. Experiences with oral treatment are only sporadically described, but observational data suggest that oral treatment could be a feasible option. The investigators have in 2010 treated 12 endocarditis patients with partial oral antibiotics with a 100% success rate.

Study design The POET study is a Danish multicenter, prospective, randomized, open label study. The primary aim is to show non-inferiority of partial oral treatment with antibiotics of endocarditis compared to full parenteral treatment. Stable patients (n=400) with streptococci, staphylococci or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, patients will be randomized to oral therapy or parenteral therapy. Special recommendations for oral treatment have been developed based on expected minimal inhibitory concentrations and pharmacokinetic calculations. Patients will be followed for 6 months after completion of antibiotic therapy. The primary endpoint is a composition of all cause mortality, unplanned cardiac surgery, embolic events and relapse of positive blood cultures with the primary pathogen.


Eligibility criteria: Inclusion Criteria:

* Left-sided endocarditis based on the Duke criteria
* Infected with one of the following microorganisms:

  * Streptococci
  * Enterococcus faecalis
  * Staphylococcus aureus
  * Coagulase-negative staphylococci.
* ≥ 18 years
* At least 10 days of appropriate parenteral antibiotic treatment overall, and at least 1 week of appropriate parenteral treatment after valve surgery
* Afebrile (T \< 38.0) \> 2 days
* Decreasing infection parameters (CRP dropped to less than 25% of peak value or \< 20 mg/l, and white blood cell count \< 15 x 109/l) during antibiotic treatment
* No sign of abscess formation by echocardiography
* Transthoracic and transoesophageal echocardiography performed within 48 hours prior to randomization

Exclusion Criteria:

* Body mass index \> 40
* Concomitant infection requiring intravenous antibiotic therapy
* Inability to give informed consent to participation
* Suspicion of reduced absorption of oral treatment due to abdominal disorder
* Reduced compliance

Primary outcomes:
measure: The primary endpoint is a composite endpoint including all cause mortality, unplanned cardiac surgery, embolic events and relapse of positive blood cultures with the primary pathogen
timeFrame: Approximately 7 months. From randomisation until 6 months after end of study medication
Secondary outcomes:
measure: Quality of life
timeFrame: Approximately 7 months. From randomisation until 6 months after end of study medication
measure: Cost of treatment
timeFrame: Approximately 7 months. From randomisation until 6 months after end of study medication
measure: Duration of antibiotic therapy
timeFrame: Approximately 7 months. From randomisation until 6 months after end of study medication
measure: Complications related to intravenous catheter
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Sygehus
city: Aarhus
country: Denmark
facility: Skejby Sygehus
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: Gentofte Hospital
city: Copenhagen
country: Denmark
facility: Herlev Hoslpital
city: Hillerød
country: Denmark
facility: Hillerød Hospital
city: Odense
country: Denmark
facility: Odense Sygehus
city: Roskilde
country: Denmark
facility: Roskilde Sygehus
Study officials:
References:
citation: Bundgaard JS, Iversen K, Pries-Heje M, Ihlemann N, Gill SU, Madsen T, Elming H, Povlsen JA, Bruun NE, Hofsten DE, Fuursted K, Christensen JJ, Schultz M, Rosenvinge F, Helweg-Larsen J, Kober L, Torp-Pedersen C, Fosbol EL, Tonder N, Moser C, Bundgaard H, Mogensen UM. Self-assessed health status and associated mortality in endocarditis: secondary findings from the POET trial. Qual Life Res. 2022 Sep;31(9):2655-2662. doi: 10.1007/s11136-022-03126-x. Epub 2022 Mar 29.
citation: Iversen K, Ihlemann N, Gill SU, Madsen T, Elming H, Jensen KT, Bruun NE, Hofsten DE, Fursted K, Christensen JJ, Schultz M, Klein CF, Fosboll EL, Rosenvinge F, Schonheyder HC, Kober L, Torp-Pedersen C, Helweg-Larsen J, Tonder N, Moser C, Bundgaard H. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan 31;380(5):415-424. doi: 10.1056/NEJMoa1808312. Epub 2018 Aug 28.
citation: Iversen K, Host N, Bruun NE, Elming H, Pump B, Christensen JJ, Gill S, Rosenvinge F, Wiggers H, Fuursted K, Holst-Hansen C, Korup E, Schonheyder HC, Hassager C, Hofsten D, Larsen JH, Moser C, Ihlemann N, Bundgaard H. Partial oral treatment of endocarditis. Am Heart J. 2013 Feb;165(2):116-22. doi: 10.1016/j.ahj.2012.11.006. Epub 2013 Jan 3.