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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Bloodstream Infection

Intervention / Treatment
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* Drug: Short-treatment of any active antibiotic regimen
* Drug: Long-treatment of any active antibiotic regimen


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment Randomized 1:1 to experimental group (short-treatment arm):control group (long-treatment arm)
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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. | 
| Mortality from any cause | Number of patients who dead from any cause from the date of inclusion to final follo-up period | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacteremia, Pseudomonas aeruginosa, Bloodstream infection, DOOR / RADAR Analysis, Antimicrobial stewardship