Partial Oral Treatment of Endocarditis (POET)

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.

Study Overview

• Status: Completed
• Conditions: Endocarditis
• Intervention / Treatment: Drug: Guideline treatment with parenteral antibiotics; Drug: Oral treatment with antibiotics for endocarditis

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Aalborg Sygehus
  • Aarhus, Denmark, 8200
    • Skejby Sygehus
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Copenhagen, Denmark
    • Gentofte Hospital
  • Copenhagen, Denmark
    • Herlev Hoslpital
  • Hillerød, Denmark
    • Hillerød Hospital
  • Odense, Denmark, 5000
    • Odense Sygehus
  • Roskilde, Denmark
    • Roskilde Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Guideline treatment with parenteral antibiotics	Drug: Guideline treatment with parenteral antibiotics
EXPERIMENTAL: Oral treatment with antibiotics; Oral treatment with antibiotics based on resistens pattern	Drug: Oral treatment with antibiotics for endocarditis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Approximately 7 months. From randomisation until 6 months after end of study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	QOL performed during the study and after completion of the study	Approximately 7 months. From randomisation until 6 months after end of study medication
Cost of treatment		Approximately 7 months. From randomisation until 6 months after end of study medication
Duration of antibiotic therapy		Approximately 7 months. From randomisation until 6 months after end of study medication
Complications related to intravenous catheter		6 weeks

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2011
• Primary Completion (ACTUAL): August 30, 2017
• Study Completion (ACTUAL): August 30, 2017

Study Registration Dates

• First Submitted: June 13, 2011
• First Submitted That Met QC Criteria: June 16, 2011
• First Posted (ESTIMATE): June 17, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 12, 2019
• Last Update Submitted That Met QC Criteria: March 9, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Endocarditis; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: Endocarditis-DK