Accelerated Treatment of Endocarditis (POET II)

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).

Study Overview

• Status: Recruiting
• Conditions: Endocarditis
• Intervention / Treatment: Other: Accelerated antibiotic treatment; Other: Standard treatment length

• Study Type: Interventional
• Enrollment (Estimated): 475
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshositalet
    • Contact: Henning Bundgaard; Phone Number: +4535450512; Email: henning.bundgaard@regionh.dk
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev Hospital
    • Contact: kasper iversen; Phone Number: +4538686009; Email: kasper.karmark.iversen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Admitted with left-sided infectious endocarditis (duke criteria)
• < 14 days of relevant antibiotic treatment for endocarditis
• One of the following bacteria: Streptococci, enterococcus faecalis, staphylococcus aureus
• > 18 years old

Exclusion Criteria:

• Known immune incompetency,
• Relapse endocarditis with 6 months,
• Unable to give informed concent

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
Experimental: Accelerated antibiotic treatment; Patients are treated shorter than usual	Other: Accelerated antibiotic treatment; 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.
Other: Standard length of antibiotic treatment; Patients are receiving the standard length of antibiotic treatment	Other: Standard treatment length; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 months after randomization
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expenses associated with admission and treatment	Combined endpoint consisting of expenses due to i admission ii medication iii transportation iv surgery v imaging vi home care	6 months after randomization
Duration of admission	Duration of admission	6 months after randomization
Duration of antibiotic treatment	Duration of antibiotic treatment	6 months after randomization
Frequency of catheter complication	Frequency of catheter complication	6 months after randomization
Unplanned Heart surgery	• Unplanned cardiac valve surgery defined as any cardiac surgery which is not planned at the time of randomization. Data will be extracted from the electronic patient journal.	6 months after randomization
All cause mortality	All cause mortality	6 months after randomization
Embolic events	Embolic events	6 months after randomization
Re-bacteremia with the primary pathogen	• Relapse of bacteremia defined as a positive blood culture with the same microorganism as during the initial IE admission (streptococci spp., S. aureus, or E. faecalis). Data will be extracted from the electronic patient journal.	6 months after randomization

Collaborators and Investigators

• Sponsor: Herlev Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Endocarditis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: H-18028566

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