Accelerated Treatment of Endocarditis (POETII)

Existing guidelines recommend a duration of antibiotic treatment of endocarditis of 4-6 weeks one or more types of intravenously administered antibiotics. The long hospitalization increases several risks for the patient, including mental strain and increased loss of function. Furthermore, it poses a significant financial burden on the health systems. Current guidelines fail to use available clinical and paraclinical, data collected from patients (echo, temperature, CRP, leukocytes, procalcitonin etc.) to determine duration of treatment. A strategy including these data in treatment algorithms ensures an individualized treatment, targeting the individual patient's course and response to treatment. Thus, the purpose of this open-label, prospective, non-inferiority, RCT study is to investigate the safety and effectiveness of shortening treatment of endocarditis based on the individual patient's initial treatment response, sampling 475 patients, approx. 125 patients with each type of bacteria (Streptococci; Enterococcus faecalis; Staphylococcus aureus). Interim analysis will be conducted when 150 patients have been included, to assess the frequency of the event rate and inclusion rate in order to adjust the intended size of the study population.

Due to an administrative error, this study has been registered twice on clinicaltrials.gov under identifiers NCT05144399 (original) and NCT03851575 (duplicate). As per July 2026, both records have been updated to unanimously reflect study status and final protocol. Historical versions of the clinicaltrials.gov registration and updates are available under the respective registration ID's (2018-2020 updates under clinicaltrials.gov registration with ID NCT05144399, 2021-2026 updates clinicaltrials.gov registration with ID NCT03851575)

Study Overview

• Status: Active, not recruiting
• Conditions: Infectious Endocarditis
• Intervention / Treatment: Other: Usual guideline therapy; Other: Accelerated treatment of endocarditis

• Study Type: Interventional
• Enrollment (Actual): 508
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Skejby Sygehus
  • Copenhagen, Denmark
    • Bispebjerg hospital
  • Copenhagen, Denmark
    • Herlev Hoslpital
  • Gødstrup, Denmark
    • Gødstrup Regional Hospital
  • Hillerød, Denmark
    • Hillerød Hospital
  • Hvidovre, Denmark
    • Hvidovre Hospital
  • Odense, Denmark, 5000
    • Odense Sygehus
  • Roskilde, Denmark
    • Roskilde Sygehus, Zealand University hospital
  • Vejle, Denmark
    • Vejle Hospital
  • Viborg, Denmark
    • Viborg Hospital
  • Denmark
    • Copenhagen, Denmark, Denmark, 2100
      • Rigshospitalet
• Sweden
  • Lund, Sweden
    • Skane University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients hospitalized and diagnosed with bacterial, left-sided endocarditis as determined by the department clinician responsible based on the revised Duke criteria.
2. The patient may be included <14 days after beginning of relevant antibiotic treatment.
3. Left-sided endocarditis with one of the following microorganisms: Streptococci; Enterococcus faecalis; Staphylococcus aureus.
4. Patients ≥ 18 years.

Exclusion Criteria:

1. Known / suspected immunocompetence (HIV, chemotherapy, prednisolone treatment (> 20 mg / day)).
2. Incapability to give informed consent for participation.
3. Relapse Endocarditis (Endocarditis with the same bacteria within six months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm; Usual guideline therapy	Other: Usual guideline therapy; E. faecalis uncomplicated: 6 weeks. E. faecalis complicated: 6 weeks. S. aureus uncomplicated: 4 weeks. S. aureus complicated: 6 weeks. Streptococci spp. NVE: 4 weeks. Streptococci spp. PVE or abscess: 6 weeks. Subsequent to cardiac surgery with a negative valve culture (organism NOT grown in laboratory from valve): Minimum 2 weeks after surgery regardless of previous antibiotic treatment received. Subsequent to cardiac surgery with a positive valve culture (organism grown in laboratory from valve): treatment will continue with the start date of antibiotics changed to the date of surgery. Complicated IE defined as patients with abscess, embolic event, surgically treated IE, and/or PVE. NVE: native valve endocarditis, PVE: prosthetic valve endocarditis.
Experimental: Accelerated arm; Accelerated treatment of endocarditis	Other: Accelerated treatment of endocarditis; E. faecalis uncomplicated: 4 weeks. E. faecalis complicated: 4 weeks. S. aureus uncomplicated: 2 weeks. S. aureus complicated: 4 weeks. Streptococci spp. NVE: 2 weeks. Streptococci spp. PVE or abscess: 3 weeks. Subsequent to cardiac surgery with a negative valve culture (organism NOT grown in laboratory from valve): Minimum 1 week after surgery regardless of previous antibiotic treatment received. Subsequent to cardiac surgery with a positive valve culture (organism grown in laboratory from valve): treatment will continue with the start date of antibiotics changed to the date of surgery. Complicated IE defined as patients with abscess, embolic event, surgically treated IE, and/or PVE. NVE: native valve endocarditis, PVE: prosthetic valve endocarditis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint: Difference in number of days alive without antibiotic treatment for endocarditits and/or bacteremia between the two study groups	The primary efficacy endpoint is the difference in number of days alive without antibiotic treatment for endocarditits and/or bacteremia between the two study groups, assessed from and until 6 months after randomization.	6 months after randomization
Combined safety endpoint of: All cause mortality, embolic episodes, not planned Heart surgery	The primary endpoint is a combined endpoint consisting of the following events occurring within six months after the earliest time of potential treatment discontinuation: Death; Embolisms; Heart surgery not planned at the time of randomization.	6 monts after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of antibiotic treatment	Duration of antibiotic treatment	6 months after randomization
Frequency of catheter complication	Frequency of catheter complication	6 months after randomization
Expenses	Expenses associated with hospitalization and treatment of the disease. I.E., expenses to admission, examinations and medicine	6 monts after randomization
Duration of hospitalization	Duration of hospitalization	6 monts after randomization
Death	Number of patients that die	6 monts after randomization
Embolisms	Number of patients that have an embolism	6 monts after randomization
Bacteraemia with the same microorganism,	Number of patients that have Bacteraemia with the same microorganism	6 monts after randomization
Surgery not planned at randomization	Number of patients that have Surgery not planned at randomization	6 monts after randomization
Quality of life assesment	Quality of life assessed by completing short version 36 (SF 36) version 2	6 monts after randomization and after

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term outcomes	1) Combined safety endpoint consisting of death, embolism or unplanned heart valve surgery, 2) days alive without antibiotic treatment for endocarditis and/or bacteremia, 3) re-bacteremia with primary pathogen	10 years from randomization

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Odense University Hospital; Zealand University Hospital; Aarhus University Hospital; Brigham and Women's Hospital; Hvidovre University Hospital; Bispebjerg Hospital; Herlev Hospital; Vejle Hospital; Gødstrup Hospital; Lund University Hospital; Nordsjaellands Hospital; Viborg Regional Hospital
• Investigators: Study Chair: Henning Bundgaard, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): April 28, 2026
• Study Completion (Estimated): April 28, 2036

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Cardiovascular Infections; Endocarditis, Bacterial; Endocarditis; Endocarditis, Subacute Bacterial
• Other Study ID Numbers: H-18028566; ID NCT05144399 (Other Identifier: clinicaltrials.gov (duplicate registration))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No