Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL)

Jacob Bodilsen, Matthijs C Brouwer, Diederik van de Beek, Pierre Tattevin, Steven Tong, Pontus Naucler, Henrik Nielsen, Jacob Bodilsen, Matthijs C Brouwer, Diederik van de Beek, Pierre Tattevin, Steven Tong, Pontus Naucler, Henrik Nielsen

Abstract

Background: The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective.

Methods: This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6-8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients.

Discussion: The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits.

Trial registration: ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019.

Keywords: Antibiotics; Brain abscess; Cerebral abscess; Intravenous; Non-inferiority; Oral; Randomized controlled trial; Treatment.

Conflict of interest statement

All authors declare no conflicts of interests for the ORAL study.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
General overview of the trial
Fig. 2
Fig. 2
Organisation of the ORAL trial
Fig. 3
Fig. 3
Flowchart of patient screening and inclusion
Fig. 4
Fig. 4
Patient timeline

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