Efficacy and Safety of 7 Versus 14 Days of Antibiotic Treatment for Pseudomonas Aeruginosa Bacteraemia (SHORTEN2)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Bloodstream Infection
• Intervention / Treatment: Drug: Short-treatment of any active antibiotic regimen; Drug: Long-treatment of any active antibiotic regimen

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.

• Study Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Hospital Universitario de A Coruña
  • Alicante, Spain, 03010
    • Hospital General Universitario Dr. Balmis
  • Almería, Spain, 04009
    • Complejo Hospitalario Torrecárdenas
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos
  • Cadiz, Spain, 11009
    • Hospital Universitario Puerta del Mar
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Granada, Spain, 18016
    • Hospital Universitario Clínico San Cecilio
  • Huelva, Spain, 21005
    • Hospital Universitario Juan Ramon Jimenez
  • Jaén, Spain, 23007
    • Complejo Hospitalario Ciudad de Jaén
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Hospital Universitario Regional de Malaga
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Valencia, Spain, 46026
    • Hospital Universitario la Fe
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Valladolid, Spain, 47003
    • Hospital Clinico Universitario de Valladolid
  • Zaragoza, Spain, 50009
    • Hospital Universitario Lozano Blesa
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 07120
      • Hospital Universitario Son Espases
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Universitario Parc Taulí
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital Universitario de Cruces
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital Universitario de Jerez de la Frontera
    • Puerto Real, Cádiz, Spain, 11510
      • Hospital Universitario de Puerto Real
  • Gipuzkoa
    • Donostia / San Sebastian, Gipuzkoa, Spain, 20014
      • Hospital Universitario DE Donostia
  • La Rioja
    • Logroño, La Rioja, Spain, 26006
      • Hospital San Pedro
  • Málaga
    • Marbella, Málaga, Spain, 29603
      • Hospital Costa del Sol
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36213
      • Complexo Hospitalario Universitario de Vigo
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short-treatment of any active antibiotic regimen; 7 days of any active antibiotic treatment from the date of the last positive blood culture	Drug: Short-treatment of any active antibiotic regimen; 7 days of any active antibiotic treatment for BSI-PA; Other Names: Any active antibiotic with treatment with proven in vitro activity from a pre-stablished list of antibiotics included
Active Comparator: Long-treatment of any active antibiotic regimen; 14 days of any active antibiotic treatment from the date of the last positive blood culture	Drug: Long-treatment of any active antibiotic regimen; 14 days of any active antibiotic treatment for BSI-PA; Other Names: Any active antibiotic with treatment with proven in vitro activity a pre-stablished list of antibiotics included

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability of achieving better DOOR/RADAR score for patients in the experimental group than in the control group	Probability of any given patient in the experimental arm to achieve better results than a patient in the control group assessed through their score in the DOOR/RADAR ( Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk) analysis. This analysis categorizes patients in two steps: A first ordinal clinical outcome ranking (DOOR), defined by the following mutually excluding categories:Healing without incidences.Healing with a proven or probable recurrence.Healing with a serious adverse event.No clinical cure.Death.; A second classification in which patients from the same clinical outcome category are ranked according to the number of days of antibiotic treatment (RADAR). Patients with a lower DOOR/RADAR score will be those with best outcomes in terms of clinical effectiveness as well as reduced exposure to antibiotic treatment.	30 days after treatment withdrawal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority secondary endpoint; Treatment failure	Defined as mortality from any cause or proven/probable recurrence	Day +30 from trial treatment interruption
Recurrence of infection	Proven, probable or possible recurrence rate	Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
Describe the superinfections	Superinfection rate	Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
Safety of antibiotic treatment	Gathering any related adverse event from the informed consent form signature up to 90 days	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.
Efficiency of the short-treatment arm	Number of days of treatment and days of hospital stay avoided at the end of the follow-up period	Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
Confirmation of origin of recurrences	Checking if the recurrences are due to the same strain, comparing the P. aeruginosa strains by genetic sequencing	Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
Comparison of ecological impact of short and long treatment regimens	Diversity of the gut microbiota analysis	Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.
Mortality from any cause	Number of patients who died from any cause from the date of inclusion to the final follow-up period	Day +30 from trial treatment interruption and day +90 from the date of extraction of the first positive blood culture.

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborators: Spanish Clinical Research Network - SCReN; CIBER (Infectious diseases)
• Investigators: Principal Investigator: José Miguel Cisneros Herreros, MD-PhD, Hospitales Universitarios Virgen del Rocío

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Bacteremia; Pseudomonas aeruginosa; Bloodstream infection; DOOR / RADAR Analysis; Antimicrobial stewardship
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Pathological Conditions, Signs and Symptoms; Bacteremia; Sepsis; Pseudomonas Infections; Anti-Infective Agents; Antitubercular Agents; Therapeutics
• Other Study ID Numbers: SHORTEN II; 2021-003847-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Final database containing only anonymous data from participant subjects will be shared with direct investigators in a timeframe of 6 months after the complete depuration
• IPD Sharing Time Frame: 6 months
• IPD Sharing Access Criteria: Direct collaborators within the study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No