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NCT Number: NCT04140903

Partial Oral Antibiotic Treatment for Bacterial Brain Abscess

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Aalborg University Hospital, Aalborg, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

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.

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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).

  9. 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

  10. 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

  11. 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)

  12. 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

  13. 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

  14. 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

  15. SAE

    Time frame: From randomisation until last day of antibiotic treatment for brain abscess

    Number of participants with severe adverse events

  16. 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)

  17. 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)

  18. 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)

  19. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Henrik Nielsen, Professor

CONTACT

[email protected]

+45 97663920

Jacob Bodilsen, MD

CONTACT

[email protected]

+45 97663920

Sponsors and collaborators

Lead sponsor

Henrik Nielsen

Other

Registry information

Official study title

Partial Oral Antibiotic Treatment for Bacterial Brain Abscess: an Open-label Randomised Non-inferiority Trial

Acronym: ORAL

Important dates

Study start
2020
Primary completion
2028
Study completion
2028
First posted
Oct 28, 2019
Registry last updated
Jan 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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