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

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Other)

Overall Status

Recruiting

CT.gov ID

NCT05210439

Collaborator

Spanish Clinical Research Network - SCReN (Other), CIBER (Infectious diseases) (Other)

306

Enrollment

Locations

Arms

40.1

Anticipated Duration (Months)

10.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Bloodstream Infection	Drug: Short-treatment of any active antibiotic regimen Drug: Long-treatment of any active antibiotic regimen	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

306 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel Assignment Randomized 1:1 to experimental group (short-treatment arm):control group (long-treatment arm)Parallel Assignment Randomized 1:1 to experimental group (short-treatment arm):control group (long-treatment arm)

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 28, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Probability of achieving better DOOR/RADAR score for patients in the experimental group than in the control group [30 days after treatment withdrawal]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain	33011
2	Hospital Universitario de Bellvitge	L'Hospitalet De Llobregat	Barcelona	Spain	08907
3	Hospital Universitario Parc Taulí	Sabadell	Barcelona	Spain	08208
4	Hospital Universitario de Cruces	Barakaldo	Bizkaia	Spain	48903
5	Hospital Universitario de Jerez de la Frontera	Jerez De La Frontera	Cádiz	Spain	11407
6	Hospital Universitario de Puerto Real	Puerto Real	Cádiz	Spain	11510
7	Hospital Universitario de Donostia	Donostia	Gipuzkoa	Spain	20014
8	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares	Spain	07120
9	Hospital San Pedro	Logroño	La Rioja	Spain	26006
10	Hospital Costa del Sol	Marbella	Málaga	Spain	29603
11	Complexo Hospitalario Universitario de Vigo	Vigo	Pontevedra	Spain	36213
12	Hospital Universitario de A Coruña	A Coruña		Spain	15006
13	Complejo Hospitalario Torrecárdenas	Almería		Spain	04009
14	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
15	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
16	Hospital Universitario Virgen de las Nieves	Granada		Spain	18014
17	Hospital Universitario Clínico San Cecilio	Granada		Spain	18016
18	Hospital Universitario Juan Ramón Jiménez	Huelva		Spain	21005
19	Complejo Hospitalario Ciudad de Jaén	Jaén		Spain	23007
20	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
21	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
22	Hospital Universitario La Paz	Madrid		Spain	28046
23	Hospital Universitario Regional de Málaga	Málaga		Spain	29010
24	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29010
25	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
26	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
27	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
28	Hospital Universitario Virgen de Valme	Sevilla		Spain	41014
29	Hospital Universitario La Fe	Valencia		Spain	46026
30	Hospital Universitario Lozano Blesa	Zaragoza		Spain	50009