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

Bloodstream Infection Clinical Trial

— SHORTEN2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05210439
• Other study ID #: SHORTEN II
• Secondary ID: 2021-003847-10
• Status: Recruiting
• Phase: Phase 4
• Start date: April 28, 2022
• Est. completion date: September 2025

Study information

• Verified date: June 2024
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: Clara M Rosso Fernández, MD-PhD
• Phone: +34955013414
• Email: claram.rosso.sspa[@]juntadeandalucia.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 306
• Est. completion date: September 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bacteremia
• Bloodstream Infection
• Pseudomonas Infections
• Sepsis

Intervention

Drug:
• Short-treatment of any active antibiotic regimen
7 days of any active antibiotic treatment for BSI-PA
• Long-treatment of any active antibiotic regimen
14 days of any active antibiotic treatment for BSI-PA

Locations

Country	Name	City	State
Spain	Hospital Universitario de A Coruña	A Coruña
Spain	Hospital General Universitario Dr. Balmis	Alicante
Spain	Complejo Hospitalario Torrecárdenas	Almería
Spain	Hospital Universitario de Cruces	Barakaldo	Bizkaia
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital Universitario Puerta del Mar	Cadiz
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario de Donostia	Donostia	Gipuzkoa
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario Juan Ramón Jiménez	Huelva
Spain	Complejo Hospitalario Ciudad de Jaén	Jaén
Spain	Hospital Universitario de Jerez de la Frontera	Jerez De La Frontera	Cádiz
Spain	Hospital Universitario de Bellvitge	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital San Pedro	Logroño	La Rioja
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Regional de Málaga	Málaga
Spain	Hospital Costa del Sol	Marbella	Málaga
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Puerto Real	Puerto Real	Cádiz
Spain	Hospital Universitario Parc Taulí	Sabadell	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Complexo Hospitalario Universitario de Vigo	Vigo	Pontevedra
Spain	Hospital Universitario Lozano Blesa	Zaragoza

Sponsors (3)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	CIBER (Infectious diseases), Spanish Clinical Research Network - SCReN

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Non-inferiority secondary endpoint; Treatment failure	Defined as mortality from any cause or proven/probable recurrence	Day +30 from trial treatment interruption
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.