Partial Oral Antibiotic Treatment for Bacterial Brain Abscess

NCT04140903 | Recruiting Phase 4 DMC

• 1 other identifier: 1
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 4

Brief Summary

The investigators aim to determine if oral antibiotics are clinically acceptable as treatment of brain abscess. Following 2 weeks of standard intravenous antibiotic therapy, half of patients will continue with this treatment for another 4 weeks or longer while the other half will be assigned to oral antibiotics for the remaining duration of treatment.

Conditions

Brain Abscess; Cerebral Abscess

Keywords

Oral antibiotics

Outcome Measures

Primary Outcomes (1)

• Treatment failure

  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 Outcomes (19)

• Treatment failure

  At last day of antibiotic treatment for brain abscess, and 3- and 12-months after randomisation

• Unfavourable outcome

  At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation

• All-cause mortality

  At last day of antibiotic treatment for brain abscess, and 3-, 6-, and 12-months after randomisation

• Unplanned neurosurgery

  At 6 months since randomisation

• IVROBA

  At 6 months since randomisation

Study Arms (2)

Oral antibiotics

EXPERIMENTAL

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

Drug: Early transition to oral antibiotics

Standard treatment

ACTIVE COMPARATOR

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

Drug: Standard treatment of intravenous antibiotics

Interventions

Early transition to oral antibiotics DRUG

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

Oral antibiotics

Standard treatment of intravenous antibiotics DRUG

Patients will continue standard intravenous antibiotic therapy for brain abscess (e.g. 3rd generation cephalosporin + metronidazole) according to international guidelines and pathogen susceptibility patterns.

Standard treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Henrik Nielsen: lead

Study Sites (4)

Aalborg University Hospital

Aalborg, Denmark

RECRUITING

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Odense University Hospital

Odense, Denmark

RECRUITING

Related Publications (1)

• Bodilsen J, Brouwer MC, van de Beek D, Tattevin P, Tong S, Naucler P, Nielsen H. Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL). Trials. 2021 Nov 12;22(1):796. doi: 10.1186/s13063-021-05783-8.

  PMID: 34772441 DERIVED

MeSH Terms

Conditions

Brain Abscess

Condition Hierarchy (Ancestors)

Central Nervous System Infections; Infections; Abscess; Suppuration; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Jacob Bodilsen, MD

  Aalborg University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob Bodilsen, MD

CONTACT

+45 97663920; jacob.bodilsen@rn.dk

Henrik Nielsen, Professor

CONTACT

+45 97663920; henrik.nielsen@rn.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: An independent blinded endpoint committee will assess the primary outcome.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Investigator-initiated, international, multi-centre, randomised, parallel groups, non-inferiority trial

Study Record Dates

• First Submitted: July 4, 2019
• First Posted: October 28, 2019
• Study Start: November 6, 2020
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months until 3 years after publication
• Access Criteria: Qualified researchers who provide a methodologically sound proposal for a post-hoc study assessed by the members of the steering committee may gain access to data after proper governmental approvals have been obtained.

Locations

DK (4)