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

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)..

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:13
Enthalten in:	Infectious diseases and therapy - 13(2023), 1 vom: 16. Dez., Seite 237-250

Sprache:	Englisch

Beteiligte Personen:

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

Links:	Volltext [kostenfrei]

Themen:	Antimicrobial resistance Antimicrobial therapy Enterobacterales Gram-negative bacilli

Anmerkungen:	© The Author(s) 2023

doi:	10.1007/s40121-023-00897-9

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	SPR054592801