Intensive Care Unit (ICU) Admission
Conditions
Keywords
ICU, Antibiotic Assesment, Diagnostic, Intervention, Medical Device, Antimicrobial Stewardship, Antimicrobial Resistance
Brief summary
The goal of this randomized clinical trial is to determine whether a biomarker-signature (BV) supported antibiotic treatment decision matrix can have a beneficial impact on antibiotic use and patient outcomes in an ICU population.
Detailed description
This study will pragmatically combine the evaluation of a diagnostic test with an antibiotic treatment decision matrix, in a manner that mimics real-life but is as close as possible to a "best-case" scenario. Primary objective is to evaluate the combined endpoint of efficacy and safety at 28 days (approximately 4 weeks). This will include: * Efficacy: Assessed by the use of antibiotics. * Safety: Assessed by clinical outcomes. Eligible participants will be randomized 1:1 to either the intervention or control groups. Evaluation of safety and efficacy will be combined to provide a global evaluation of the benefits and risks of the intervention, using the Desirability of Outcome Ranking (DOOR) further combined with Response Adjusted for Duration of Antibiotic Risk (RADAR). The hypothesis is that participants in the intervention group will have lower antibiotic exposure, without increased harm (worse clinical outcomes related to infection or significant adverse events) .
Interventions
DIAGNOSTIC_TESTBiomarker-signature supported antibiotic treatment recommendation
The antibiotic treatment recommendation will be based on a decision matrix that combines the results of the BV-signature (a score ranging from 0 -100) with the clinical assessment of likelihood of bacterial infection.
DIAGNOSTIC_TESTClinical assessment for antibiotic treatment decision
Antibiotic treatment decision will be based on clinical assessment only (BV test result remains masked)
Sponsors
McGill University Health Centre/Research Institute of the McGill University Health Centre
Canadian Institutes of Health Research (CIHR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
All team members and participants remain blinded during the Enrollment and Clinical Assessment Stages. The study team, (PI/CO-Is that are ID physicians, pharmacist, and laboratory technologist performing BV testing), will remain blinded while conducting the clinical assessment and laboratory testing. The results of the MeMed BV diagnostic test will only be disclosed for participants in the experimental group but not for those in the control group. The study and treating team will be informed of the treatment group assignment when the intervention begins, specifically when the clinical assessment is completed.
Intervention model description
Pivotal Study, Observer-Blind, Randomized Control Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to the Intensive Care Unit (ICU) * Started on antibiotics for any suspected or confirmed infection in the preceding 72 hours (about 3 days) * Treating doctor(s) willing to consider BV test result in antibiotic treatment decision making
Exclusion criteria
* Severe immunocompromise/immunosuppression 1. Congenital immunodeficiency 2. HIV with CD4 \< 20 3. Active chemotherapy and profound neutropenia (ANC \< 100) expected to last \> 7 days; 4. solid organ or stem cell transplant within preceding 6 months AND active GVHD 5. Receiving high dose steroids (Pred \> 20mg/day for \> or = 2 weeks) * Advanced metastatic cancer irrespective of treatment * Palliative intent, death imminent and inevitable within 4 weeks * Antibiotic to be discontinued within 24h (ex. Prophylaxis) * Active infection diagnosed and treated with antibiotics within preceding 2 weeks * Previously included during the same hospitalization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Desirability of Outcome Ranking Adjusted for Antibiotic Risk (DOOR-RADAR) | 28 days+/- 2 | The primary outcome is the Desirability of Outcome Ranking (DOOR), which ranks each participant according to overall clinical outcome based on a hierarchical composite that incorporates mortality, infection recurrence, infection relapse and treatment-related adverse events. Participants are assigned to mutually exclusive outcome ranks (1 to 5), with 1 representing the most desirable outcome (alive, none of treatment failure/recurrence or adverse events) and 5 representing the least desirable outcome (death). Within each clinical outcome category, participants will be further ranked according to antibiotic exposure using the Response Adjusted for Duration of Antibiotic Risk (RADAR) approach, such that shorter duration of antibiotic therapy is considered more desirable. The primary analysis will estimate the probability that a randomly selected participant in the intervention group has a more desirable outcome than a participant in the comparator group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of stay in the Intensive Care Unit | 28 +/- 2 days | Duration of stay in the intensive care unit, measured in days from ICU admission to ICU discharge. |
| All cause mortality | 28 +/- 2 days | Death from any cause during the follow-up period. |
| Days of antibiotic therapy (DOT) | 28 +/- 2 days | Total number of days each participant received systemic antibacterial therapy during the study period. |
| Antibiotic-free days | 28 days+/- 2 | Number of days alive and not receiving systemic antibiotic therapy during the follow-up period. |
| Adverse events | 28 +/- 2 days | Number of participants experiencing treatment-related adverse events during the follow-up period, including serious adverse events. |
Countries
Canada
Contacts
CONTACTMakeda Semret, MD
Outcome results
None listed