- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04140903
Partial Oral Antibiotic Treatment for Bacterial Brain Abscess (ORAL)
Partial Oral Antibiotic Treatment for Bacterial Brain Abscess: An Open-label Randomised Non-inferiority Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Treatment of brain abscess remains a considerable challenge due to the precarious location of the infection and the impenetrability of the blood-brain-barrier for most drugs. Thus, cure usually requires a combination of neurosurgical evacuation of abscess material and 6-8 weeks of high-dose intravenous (IV) antibiotic therapy to ensure eradication of bacteria within the abscess cavity. Disadvantages include risks of nosocomial infections and line-associated complications (e.g. bleeding, venous thrombosis, or need for replacement due to malfunction) in addition to the considerable costs of such long-term admission. However, improved insights into the pharmacokinetic properties and favourable bioavailability of some oral antibiotics may allow such treatment at an early stage. To date, there are no randomised controlled trials to guide treatment of bacterial brain abscess.
The investigators wish to determine whether a treatment strategy of transition to oral antibiotics after two weeks of treatment is non-inferior to continued IV antibiotics in clinically stable brain abscess patients assessed by the proportion with a favourable outcome at six months since randomisation.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Jacob Bodilsen, MD
- Phone Number: +45 97663920
- Email: jacob.bodilsen@rn.dk
Study Contact Backup
- Name: Henrik Nielsen, Professor
- Phone Number: +45 97663920
- Email: henrik.nielsen@rn.dk
Study Locations
-
-
-
Aalborg, Denmark
- Recruiting
- Aalborg University Hospital
-
Contact:
- Jacob Bodilsen, MD PhD
-
Aarhus, Denmark
- Recruiting
- Aarhus University Hospital
-
Contact:
- Merete Storgaard, MD
-
Copenhagen, Denmark
- Recruiting
- Rigshospitalet
-
Contact:
- Lars H Omland, MD
-
Odense, Denmark
- Recruiting
- Odense University Hospital
-
Contact:
- Lykke Larsen, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- A clinical presentation (e.g. headache, neurological deficit or fever) and cranial imaging (CT or MRI) consistent with brain abscess AND
- The physician responsible for the patient decides to treat the patient for bacterial brain abscess AND
- Ability to take and absorb oral medications (including by nasogastric tube) AND
- To have received relevant antibiotic therapy for bacterial brain abscess for 14 consecutive days before randomisation AND
- Expected to be treated with antibiotic therapy for at least another 14 days after time of randomisation AND
- No progression in symptom intensity or occurrence of new-onset neurological symptoms (excluding seizures) within five days before time of randomisation.
Exclusion Criteria (patients fulfilling either criteria):
- Expected substantially reduced compliance with treatment (e.g. IV drug abuse)
- Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women <50 years of age)
- Concomitant (empirical) brain abscess treatment for tuberculosis, nocardiosis, Pseudomonas spp., fungi, toxoplasmosis or other CNS parasites
- Device related brain abscesses (e.g. deep brain stimulators, ventriculo-peritoneal shunts)
- Severe immuno-compromise defined as ongoing need for biological- or chemotherapy, prednisolone >20 mg/day for 14 days or longer, uncontrolled HIV/AIDS, haematological malignancies, and organ transplant recipients
- Concomitant or unrelated infections necessitating IV antibiotics beyond seven days of duration after time of randomisation
- Previous enrolment into this trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Oral antibiotics
Patients will be randomised to oral antibiotics after two weeks of appropriate antibiotic therapy for bacterial brain abscess since definitive aspiration/excision of brain abscess or, in case of no planned diagnostic neurosurgical procedure, since initiation of guideline recommended antibiotics for bacterial brain abscess
|
Patients will be treated with an oral antibiotic regimen (e.g.
amoxicillin + metronidazole) based upon pharmacokinetic and pharmacodynamic properties of the drugs, pathogen susceptibility, and any existing drug allergies or interactions
|
Active Comparator: Standard treatment
Patients will be randomised to continuation of standard intravenous antibiotics after two weeks of appropriate antibiotic therapy for bacterial brain abscess since definitive aspiration/excision of brain abscess or, in case of no planned diagnostic neurosurgical procedure, since initiation of guideline recommended antibiotics for bacterial brain abscess
|
Patients will continue standard intravenous antibiotic therapy for brain abscess (e.g.
3rd generation cephalosporin + metronidazole) according to international guidelines and pathogen susceptibility patterns.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment failure
Time Frame: Six months after randomisation
|
A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence
|
Six months after randomisation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment failure
Time Frame: At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation
|
A composite of number of participants with all-cause mortality, risk of intraventricular rupture of brain abscess (IVROBA), unplanned neurosurgery, relapse, or recurrence
|
At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation
|
Unfavourable outcome
Time Frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
|
Number of participants with Extended Glasgow Outcome Scale score <7, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)
|
At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
|
All-cause mortality
Time Frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
|
Number of participants with fatal outcome, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)
|
At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
|
Unplanned neurosurgery
Time Frame: At 6 months since randomisation
|
Number of participants with unplanned (re-)aspiration or excision, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)
|
At 6 months since randomisation
|
IVROBA
Time Frame: At 6 months since randomisation
|
Number of participants with intraventricular rupture of brain abscess, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)
|
At 6 months since randomisation
|
Relapse
Time Frame: At 6 months since randomisation
|
Number of participants with increase in brain abscess volume by 20% since randomisation, clinical deterioration attributable to brain abscess or lack of cure of at least 4 weeks or longer of assigned study treatment, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)
|
At 6 months since randomisation
|
Recurrence
Time Frame: At 6 months since randomisation
|
New brain abscess formation after end of treatment, overall and stratified by study centre, oral cavity bacteria (yes/no) and largest brain abscess diameter (+/- 3 cm)
|
At 6 months since randomisation
|
Unfavourable outcome - sliding dichotomy
Time Frame: At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
|
Sliding dichotomy of extended Glasgow Outcome Scale scores according to Charlson comorbidity index score (range: 0=no comorbidity and more likely to have a favourable outcome to 40=high degree of comorbidity with a poor prognosis of a favourable outcome) at time of randomisation (0 vs. 1-2 vs. >2).
|
At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation
|
Central line associated complications
Time Frame: 6 months since randomisation
|
Number of participants with bleeding, infection, venous thrombosis or need for replacement of central line due to mechanical malfunction
|
6 months since randomisation
|
Clostridial diarrhea
Time Frame: From randomisation up until last day antibiotic treatment for brain abscess
|
Number of participants who develop Clostridioides difficile associated gastro-enteritis during antibiotic treatment for brain abscess
|
From randomisation up until last day antibiotic treatment for brain abscess
|
Duration of admission
Time Frame: From randomisation until hospital discharge to home or rehabilitation unit or death, whichever comes first, assessed up to 6 months
|
Days spent as admitted patient in hospital up to 6 months since randomisation (does not include outpatient hospital care)
|
From randomisation until hospital discharge to home or rehabilitation unit or death, whichever comes first, assessed up to 6 months
|
Duration of treatment
Time Frame: From randomisation until last day of antibiotic treatment for brain abscess up to 6 months since randomisation
|
Number of days treated with antibiotics for brain abscess up to 6 months since randomisation
|
From randomisation until last day of antibiotic treatment for brain abscess up to 6 months since randomisation
|
Adherence to treatment
Time Frame: From randomisation until last day of antibiotic treatment for brain abscess, assessed up to 6 months since randomisation
|
Adherence to allocated treatment.
For oral treatment this will be measured using Morisky 8-item Medication Adherence scale scores (range 0=high adherence to 8=low adherence) up to 6 months since randomisation
|
From randomisation until last day of antibiotic treatment for brain abscess, assessed up to 6 months since randomisation
|
Oedema on cranial imaging
Time Frame: 3 months since randomisation
|
Number of participants with residual perilesional oedema on cranial imaging up to 3 months since randomisation
|
3 months since randomisation
|
SAE
Time Frame: From randomisation until last day of antibiotic treatment for brain abscess
|
Number of participants with severe adverse events
|
From randomisation until last day of antibiotic treatment for brain abscess
|
SF36
Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
Short Form 36 is a 36 item survey of patient-reported health-related quality of life (range 0=maximum disability to 100=no disability)
|
At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
EQ-5D-5L
Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
EuroqQol - 5 dimensions - 5 level scores are derived from a standardized instrument for measuring generic health status including mobility, self-care, usual acitivities, pain/discomfort, and anxiety/depression (range 5=good health status to 25=poor health status)
|
At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
EQ-VAS
Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
EuroqQol Visual Analogue Scale (range 0=poor health status to 100=excellent health status)
|
At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
Cognitive impairment
Time Frame: At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
Montreal Cognitive Assessment (MoCA) scores (range 0=poor cognitive performance to 30=normal cognitive performance)
|
At time of randomisation, last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months since randomisation
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jacob Bodilsen, MD, Aalborg University Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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