This study has been transitioned to CTIS with ID 2023-505483-11-00 check the CTIS register for the current data. To investigate if early transition to oral treatment after two weeks or longer of IV antibiotic therapy is non-inferior to standard six…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Central nervous system infections and inflammations
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Treatment failure at 6 months after randomisation, consisting of:
1. All-cause mortality
2. Intraventricular rupture of brain abscess
3. Unplanned re-aspiration or excision of brain abscess
4. Relapse or recurrence
Secondary outcome
1. Extended Glasgow Outcome Scale scores and all-cause mortality at end of
treatment as well as 3-, 6-, 12-months since randomisation
2. Completion of assigned treatment (oral vs. IV)
3. Line associated complications (infection, thrombosis, bleeding or need for
replacement)
4. Durations of admission and antibiotic treatment
5. Serious adverse events
6. Quality of life scores and cognitive evaluations.
Background summary
A brain abscess is a serious infection with a considerable impact on patients*
lives. Treatment remains a challenge due to the precarious location of the
infection and the impenetrability of the blood-brain-barrier for most drugs.
Thus, a favourable outcome usually requires a combination of neurosurgical
evacuation of the abscess and prolonged high-dose antibiotic therapy to ensure
eradication of bacteria within the abscess cavity. However, there are no
randomised controlled trials on antibiotic treatment of brain abscess to
support the standard regimen of 6-8 weeks intravenous treatment.
Reports of treatment failure, relapse and recurrence are very rare with current
treatment recommendations. However, the long duration of IV treatment is often
strenuous for patients to endure with associated discomfort of long-term
admission, risks of hospital-acquired infections, and line complications
(infection, bleeding, venous thrombosis, and need for line replacement due to
malfunction). In addition, costs associated with such prolonged admissions are
significant.
A shortened IV treatment for bacterial brain abscess has been reported to be
successful in retrospective observational studies. However, properly controlled
trials are needed to examine this treatment strategy in bacterial brain abscess
patients.
Study objective
This study has been transitioned to CTIS with ID 2023-505483-11-00 check the CTIS register for the current data.
To investigate if early transition to oral treatment after two weeks or longer
of IV antibiotic therapy is non-inferior to standard six weeks or longer of IV
antibiotic treatment for bacterial brain abscess.
Study design
This is an investigator initiated, open-label, interventional (1:1 allocation),
international, multicentre, parallel group, randomised, controlled,
non-inferiority trial comparing two treatment strategies.
Intervention
One group will continue with intraveneus treatment, the other group will switch
to oral antibiotics.
Study burden and risks
Participation in the study does include a few extra outpatient visits that may
not be part of routine treatment. Patients assigned to early switch to oral
therapy may have a theoretical increased risk of treatment failure, which could
lead to complications and prolonged duration of treatment.The oral antibiotics
used in this study are all approved and well-known for treatment of numerous
infectious diseases in every day clinical care. There are no increased risks
for patients randomised to standard treatment.
Patients randomised to oral therapy may be candidates for early discharge and
thereby spend considerably less time at hospital. As such, risks associated
with long-term hospital admission (hospital-acquired infections, loss of daily
life functions) and extended IV treatment (bleeding, infection, venous
thrombosis, need for catheter replacement, development of bacterial resistance
in the hospital environment) are decreased. For patients assigned to standard
treatment there will be no changes to usual care.
Fredrik Bajers Vej 7K
Aalborg 9220
DK
Fredrik Bajers Vej 7K
Aalborg 9220
DK
Listed location countries
Age
Inclusion criteria
Adults >=18 years of age with bacterial brain abscess defined as:
1. A clinical presentation (e.g. headache, neurological deficit or fever) and
cranial imaging (CT or MRI) consistent with brain abscess according to the
hospital radiologist AND
2. The physician responsible for the patient decides to treat the patient for
bacterial brain abscess
Further requirements for inclusion are:
3. Ability to absorb oral medications (including by nasogastric tube)
4. To have received guideline recommended empiric or targeted (according to in
vitro susceptibility) IV antibiotic therapy for bacterial brain abscess for 14
consecutive days or longer before randomisation and no additional aspiration or
excision of brain abscess planned
5. Expected to be treated with antibiotic therapy for at least another 14 days
after time of randomisation
6. No progression in neurological deficits or occurrence of new-onset
neurological symptoms (excluding seizures) within five days before time of
randomisation
Exclusion criteria
1. Hypersensitivity to an antibiotic intended for use in the patient and no
alternative drugs available.
2. Expected substantially reduced compliance with treatment
3. Pregnancy/ lactating women.
4. Concomitant treatment for proven or suspected CNS infection caused by
mycobacteria, Nocardia spp., Pseudomonas spp., fungi, toxoplasmosis or other
CNS parasites
5. Device related brain abscesses (e.g. deep brain stimulators,
ventriculo-peritoneal shunts)
6. Severe immuno-compromise defined as ongoing need for biological- or
chemotherapy, prednisolone >20 mg/day for >=14 days, uncontrolled HIV/AIDS (see
Glossary), haematological malignancies (see Glossary), and organ transplant
recipients
7. Concomitant or unrelated infections necessitating IV antibiotics beyond
seven days of duration after time of randomisation
8. Brain abscesses caused by Staphylococcus Aureus
9. Previous enrolment into this trial
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-505483-11-00 |
| ClinicalTrials.gov | NCT04140903 |
| CCMO | NL76390.018.22 |