TY - JOUR
T1 - Partial oral antibiotic treatment for bacterial brain abscess
T2 - an open-label randomized non-inferiority trial (ORAL)
AU - Bodilsen, Jacob
AU - Brouwer, Matthijs C.
AU - van de Beek, Diederik
AU - Tattevin, Pierre
AU - Tong, Steven
AU - Naucler, Pontus
AU - Nielsen, Henrik
N1 - Funding Information: The study has been funded by the Novo Nordisk Foundation (Grant 0057510). The funder will play no part in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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
AB - 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
KW - Antibiotics
KW - Brain abscess
KW - Cerebral abscess
KW - Intravenous
KW - Non-inferiority
KW - Oral
KW - Randomized controlled trial
KW - Treatment
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85119058170&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34772441
U2 - https://doi.org/10.1186/s13063-021-05783-8
DO - https://doi.org/10.1186/s13063-021-05783-8
M3 - Article
C2 - 34772441
SN - 1745-6215
VL - 22
JO - Trials
JF - Trials
IS - 1
M1 - 796
ER -