A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol

Beatriz Arns, Jaqueline Driemeyer C. Horvath, Gabriela Soares Rech, Guilhermo Prates Sesin, Crepin Aziz Jose Oluwafoumi Agani, Bruna Silveira da Rosa, Tiago Marcon dos Santos, Liliane Spencer Bittencourt Brochier, Alexandre Biasi Cavalcanti, Bruno Martins Tomazini, Adriano Jose Pereira, Viviane Cordeiro Veiga, Giovana Marssola Nascimento, Andre C. Kalil, Alexandre P. Zavascki

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Shorter courses of antimicrobials have been shown to be non-inferior to longer, “traditional” duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. Methods: This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. Planned Outcomes: The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. Conclusion: The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. Trial Registration: ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).

Original languageEnglish (US)
Pages (from-to)237-250
Number of pages14
JournalInfectious Diseases and Therapy
Volume13
Issue number1
DOIs
StatePublished - Jan 2024

Keywords

  • Acinetobacter baumannii
  • Antimicrobial resistance
  • Antimicrobial therapy
  • Enterobacterales
  • Gram-negative bacilli
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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