Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06323668 |
| Other study ID # |
H-23067693 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2024 |
| Est. completion date |
January 31, 2038 |
Study information
| Verified date |
March 2024 |
| Source |
Rigshospitalet, Denmark |
| Contact |
Emil L Fosbøl, MD, PhD |
| Phone |
+4535456340 |
| Email |
emil.fosboel[@]regionh.dk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The CIEDOUT study is an open label randomized trial in patients with possible cardiac
implantable electronic device (CIED) infection.
The hypothesis is that CIED removal + guideline antibiotic therapy is better than 6-weeks
antibiotic therapy alone in preventing death or relapse of bacteremia in patients with
bacteremia and possible CIED infection (not definite CIED infection).
The objective of this study is to test whether CIED removal + guideline antibiotic therapy is
superior to 6-weeks antibiotic therapy alone in prevention of the composite endpoint of death
or relapse bacteremia after 6 months of follow-up in patients with CIED and systemic
infection but without definite CIED infection.
Description:
Complete removal of cardiac implantable electronic devices (CIEDs) is recommended for all
patients with confirmed CIED infection under initial empirical antibiotic therapy by
guidelines. However, the current 2023 European Society of Cardiology (ESC) guidelines on
treatment of possible CIED infection are mostly based on expert opinions and/or observational
studies. No previous randomized clinical trial has been conducted, why the CIEDOUT study is
the first randomized clinical trial with high evidence investigating treatment of possible
CIED infections. The CIEDOUT study will affect future clinical guidelines and optimize
treatment and prognosis for future patients with possible CIED infection.
The hypothesis is that CIED removal + guideline antibiotic therapy is superior to 6-weeks
antibiotic therapy alone in preventing death or relapse of bacteremia in patients with
bacteremia and possible CIED infection (not definite CIED infection). The investigators want
to test whether CIED removal + guideline antibiotic therapy is superior to 6-weeks antibiotic
therapy in prevention of the composite endpoint of death or relapse bacteremia after 6 months
of follow-up in patients with CIED and systemic infection but without definite CIED
infection.
The study is a randomized open label trial. Patients will be allocated by 1:1 randomization
to CIED extraction + guideline antibiotic therapy or 6-weeks antibiotic therapy alone. The
primary outcome is a composite endpoint of death or relapse bacteremia (same microorganism)
within 6 months after randomization. The secondary outcomes are days alive and
out-of-hospital to 6 months, death, readmission for any cause, device extraction, relapse of
bacteremia (the same microorganism), relapse of bacteremia (all species), and definite CIED
infection.
All patients suspected of CIED infection or patients with bacteremia + CIED will be screened
for inclusion in the CIEDOUT study according to the ESC modified diagnosis criteria. To
enable timely identification of possible candidates, a surveillance system will be set up
combining data from The Danish Pacemaker and implantable cardioverter-defibrillator (ICD)
registry and then real-time bacteremia surveillance data through The Danish nationwide
clinical Microbiology Database (MiBa). Hence, whenever a relevant bacteremia is identified,
the CIED registry will then by queried for whether that patient also has CIED. Randomization
allocation ratio is 1:1 through a computerized application via RedCap. Patients will be
entered into the "intention to treat" analysis.
The patients will be randomized to CIED removal and/or medical therapy (at least 10 days iv
antibiotic therapy and then per oral treatment to 6 weeks total by POET criteria). The CIED
removal will be done as soon as possible within 7 days. The study-outcomes will be assessed
at three routine clinical check-ups as part of the standard treatment at 1 week, 4 weeks, and
3 months after randomization. Within 6 months after randomization, patients will be followed
for outcomes through medical charts and the national health registries. After that, the
patients will be assessed for outcomes on an annual basis by medical chart review and the
Danish nationwide registries.
The total trial duration is expected to be 14 years. Inclusion period for the main paper is
expected to be 4 years and then follow-up for 3 months for the last included patients.
Hereafter, patients will be followed for outcomes annually through medical charts and the
national health registries up to 10 years after the last included patient until 2038.
Based on prior studies and especially preliminary data, it is estimated that approximately
29% of patients will experience a primary event by 6 months in the medical treatment group
and 12% in the extraction group. In order to have 80% power to detect difference in total
primary endpoints between the treatment groups, at least 174 patients will be needed (87 in
each study arm) over a median follow-up of 3 years to be able to reject the null hypothesis
with a power of 80% and a risk of type I error of 5. Assuming a steady rate of patients with
the inclusion criteria, there will be approximately 100 incident cases available for the
CIEDOUT study annually in Eastern Denmark based on preliminary data. If 60% of these consent
to the study, 60 incident patients per year will be included. By 3 years, 180 incident
patients will then be included.
