Accelerated Treatment of Endocarditis

NCT03851575 | Active Not Recruiting DMC

• 2 other identifiers: H-18028566ID NCT05144399
• Study Type: interventional
• Target: 508
• Locations: 3 countries
• Sites: 13

Brief Summary

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)

Conditions

Infectious Endocarditis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (9)

• Expenses

  6 monts after randomization

• Duration of antibiotic treatment

  6 months after randomization

• Duration of hospitalization

  6 monts after randomization

• Frequency of catheter complication

  6 months after randomization

• Surgery not planned at randomization

  6 monts after randomization

Other Outcomes (1)

• Long-term outcomes

  10 years from randomization

Study Arms (2)

Control arm

ACTIVE COMPARATOR

Usual guideline therapy

Other: Usual guideline therapy

Accelerated arm

EXPERIMENTAL

Accelerated treatment of endocarditis

Other: Accelerated treatment of endocarditis

Interventions

Accelerated treatment of endocarditis OTHER

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.

Accelerated arm

Usual guideline therapy OTHER

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.

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Herlev Hospital: collaborator
• Nordsjaellands Hospital: collaborator
• Zealand University Hospital: collaborator
• Odense University Hospital: collaborator
• Aarhus University Hospital: collaborator
• Lund University Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Hvidovre University Hospital: collaborator
• Vejle Hospital: collaborator
• Viborg Regional Hospital: collaborator
• Gødstrup Hospital: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (13)

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Rigshospitalet

Copenhagen, Denmark, 2100, Denmark

Location

Skejby Sygehus

Aarhus, 8200, Denmark

Location

Bispebjerg Hospital

Copenhagen, Denmark

Location

Herlev Hoslpital

Copenhagen, Denmark

Location

Gødstrup Regional Hospital

Gødstrup, Denmark

Location

Hillerød Hospital

Hillerød, Denmark

Location

Hvidovre Hospital

Hvidovre, Denmark

Location

Odense Sygehus

Odense, 5000, Denmark

Location

Roskilde Sygehus, Zealand University hospital

Roskilde, Denmark

Location

Vejle Hospital

Vejle, Denmark

Location

Viborg Hospital

Viborg, Denmark

Location

Skåne University Hospital

Lund, Sweden

Location

MeSH Terms

Conditions

Endocarditis, Subacute Bacterial

Condition Hierarchy (Ancestors)

Endocarditis, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Cardiovascular Infections; Cardiovascular Diseases; Endocarditis; Heart Diseases

Study Officials

• Henning Bundgaard, MD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: February 22, 2019
• Study Start: January 17, 2019
• Primary Completion: April 28, 2026
• Study Completion (Estimated): April 28, 2036
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (11); SE (1); US (1)