Clinical trial NCT05210439: Efficacy and Safety of 7 Versus 14 Days of Antibiotic Treatment for Pseudomonas Aeruginosa Bacteraemia
Official title: Efficacy and Safety of 7 Versus 14 Days of Antibiotic Treatment for Pseudomonas Aeruginosa Bacteremia: a Multicenter, Randomized Clinical Trial (SHORTEN-2) With a DOOR / RADAR Analysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Bloodstream Infection
Keywords: Bacteremia
Pseudomonas aeruginosa
Bloodstream infection
DOOR / RADAR Analysis
Antimicrobial stewardship
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Spanish Clinical Research Network - SCReN
name: CIBER (Infectious diseases)
First posted: 2022-01-27
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment Randomized 1:1 to experimental group (short-treatment arm):control group (long-treatment arm)
Primary purpose: TREATMENT

Brief summary: Phase IV, open-labeled, randomized and multicenter clinical trial to demonstrate the superiority of antibiotics with authorized indication for 7 days versus 14 days in the treatment of bloodstream infections produced by P. aeruginosa (BSI-PA).

Detailed description: The project is designed to determine the optimal duration of antibiotic treatment for Pseudomonas aeruginosa bacteremia, by comparing an adequate antibiotic treatment regimen of 7 days (experimental arm) with another of 14 days (control arm). The evaluation of infection recurrences, mortality, number of free days of antibiotic treatment, adverse events and superinfections are included as secondary objectives.

Active antibiotic treatment will be considered any treatment with proven in vitro activity against the strain responsible for the patient's bacteremia, regardless of the administered dose.

Clinical rules are included in order to stop antibiotic treatment or continuation and re-evaluation in each arm of treatment.

This is a pragmatic study as the number or visits performed for the study are similar to the normal clinical follow-up for this patients. Final contact and final visit for the study will be performed at 90 days after the first positive blood culture.

Eligibility criteria: Main inclusion criteria:

* Adult patients with diagnosis of BSI-PA who have received 6 days (+/- 1) of active antibiotic treatment from the date of extraction of the first positive blood culture and until the moment of randomization.
* Informed consent signed.

Main exclusion criteria:

* Bacteremia source not adequately controlled at least 72h before randomization.
* Bacteremia secondary to an infection that necessarily requires prolonged antibiotic treatment more than 7 days
* Coexistence of a different infection at the time of diagnosis of bacteremia that also requires antibiotic treatment.
* Bacteremic pneumonia in severely immunosuppressed patients
* Bacteremia of any origin in patients with severe neutropenia (\<500 cells / mm3) at the time of randomization.

Primary outcomes:
measure: Probability of achieving better DOOR/RADAR score for patients in the experimental group than in the control group
timeFrame: 30 days after treatment withdrawal
Secondary outcomes:
measure: Non-inferiority secondary endpoint; Treatment failure
timeFrame: Day +30 from trial treatment interruption
measure: Recurrence of infection
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
measure: Mortality from any cause
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
measure: Describe the superinfections
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
measure: Safety of antibiotic treatment
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture and weighted by 1,000 days of follow-up.
measure: Efficiency of the short-treatment arm
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
measure: Confirmation of origin of recurrences
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
measure: Comparison of ecological impact of short and long treatment regimens
timeFrame: Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Sabadell
country: Spain
facility: Hospital Universitario Parc Taulí
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Bizkaia
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
state: Cádiz
city: Puerto Real
country: Spain
facility: Hospital Universitario de Puerto Real
state: Cádiz
city: Donostia
country: Spain
facility: Hospital Universitario de Donostia
state: Gipuzkoa
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Logroño
country: Spain
facility: Hospital San Pedro
state: La Rioja
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Vigo
country: Spain
facility: Complexo Hospitalario Universitario de Vigo
state: Pontevedra
city: A Coruña
country: Spain
facility: Hospital Universitario de A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Almería
country: Spain
facility: Complejo Hospitalario Torrecárdenas
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramón Jiménez
city: Jaén
country: Spain
facility: Complejo Hospitalario Ciudad de Jaén
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Zaragoza
country: Spain
facility: Hospital Universitario Lozano Blesa
Study officials:
affiliation: Hospitales Universitarios Virgen del Rocío
name: José Miguel Cisneros Herreros, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Molina J, Rosso-Fernandez CM, Montero-Mateos E, Pano-Pardo JR, Solla M, Guisado-Gil AB, Alvarez-Marin R, Pachon-Ibanez ME, Gimeno A, Martin-Gutierrez G, Lepe JA, Cisneros JM; SHORTEN-2 trial team. Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial). PLoS One. 2022 Dec 22;17(12):e0277333. doi: 10.1371/journal.pone.0277333. eCollection 2022.