Bloodstream Infection
Conditions
Keywords
Bacteremia, Pseudomonas aeruginosa, Bloodstream infection, DOOR / RADAR Analysis, Antimicrobial stewardship
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.
Interventions
DRUGShort-treatment of any active antibiotic regimen
7 days of any active antibiotic treatment for BSI-PA
DRUGLong-treatment of any active antibiotic regimen
14 days of any active antibiotic treatment for BSI-PA
Sponsors
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Spanish Clinical Research Network - SCReN
CIBER (Infectious diseases)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment Randomized 1:1 to experimental group (short-treatment arm):control group (long-treatment arm)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: 1. A first ordinal clinical outcome ranking (DOOR), defined by the following mutually excluding categories: 1. Healing without incidences. 2. Healing with a proven or probable recurrence. 3. Healing with a serious adverse event. 4. No clinical cure. 5. Death. 2. 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
| Measure | Time frame | Description |
|---|---|---|
| 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 died from any cause from the date of inclusion to the final follow-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 |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORJosé Miguel Cisneros Herreros, MD-PhD
Hospitales Universitarios Virgen del Rocío
Outcome results
None listed