Critical Illness, Neoplasm, Sepsis, Septic Shock
Conditions
Keywords
Procalcitonin, Sepsis, Septic shock, Cancer, Critical illness
Brief summary
Studies have demonstrated that the use of a procalcitonin (PCT)-guided algorithm in combination with clinical judgment was associated with reduced antibiotic use without impacting mortality or treatment failure. Though several studies have evaluated the use of PCT in critically ill patients, there are limited studies that evaluated PCT in patients with cancer and many of the currently available studies have excluded immune-compromised patients. This is a randomized controlled trial that aims to evaluate the impact of a procalcitonin-guided algorithm on antibiotic utilization in critically ill cancer patients with sepsis. In addition, the study aims to evaluate the predictive value of PCT for predicting mortality and positive cultures.
Detailed description
Procalcitonin (PCT) has been widely studied to guide antibiotic use in critically ill septic patients. Using an algorithm for antibiotic de-escalation guided by PCT levels in septic patients with respiratory tract infections was associated with lower antibiotics exposure without increasing mortality or treatment failure. Furthermore, the current Surviving Sepsis Guidelines suggest that PCT levels may help clinicians in their decision of empiric antibiotics discontinuation especially in patients with suspected sepsis and low PCT values with no other evidence of infection (low level of evidence, GRADE 2C). Reducing the use of antibiotics is a global health care priority. Using a PCT-guided algorithm in combination with clinical judgment was associated with reduced antibiotic use without increasing morbidity or mortality. Though PCT has been widely studied as a diagnostic, prognostic, and theragnostic inflammatory marker in patients with sepsis, there are limited studies that evaluated PCT in patients with cancer and many of the currently available studies have excluded immune-compromised patients. Furthermore, studies have reported elevated inflammatory markers, including PCT, in patients with cancer as a result of the malignancy itself or treatment complications. This may suggest that PCT alone may possibly be less useful for differentiating infectious from non-infectious sources of fever in cancer patients. However, serial PCT levels may be more useful in cancer patients, compared to a single level. Sepsis is common in cancer patients; however, there are limited studies evaluating the clinical impact of obtaining PCT levels in this patient population. Therefore, this study will evaluate the impact of obtaining serial PCT levels on the number of antibiotic days in cancer patients with sepsis. In addition, the study aims to evaluate the predictive value of PCT for predicting mortality and positive cultures. Study Objectives The main objective of this study is to evaluate the impact of a PCT-guided algorithm on the duration of antimicrobial therapy in critically ill cancer patients with sepsis. The main research question being asked is whether providing the clinical team with daily PCT levels, along with a PCT-based algorithm to guide antimicrobial management, would have an impact on the duration of antibiotic therapy. In addition, the study intends to assess the role of PCT in predicting mortality and positive cultures in the cancer septic patient population.
Interventions
DIAGNOSTIC_TESTProcalcitonin Levels
Procalcitonin (PCT) will be measured within 48 hours of admission to the ICU or 48 hours of onset of sepsis (if developed during the ICU stay). In addition, the patients will have daily blood samples taken up to 5 days or until ICU transfer, whichever occurs first. A PCT-guided algorithm will be available to guide the management of patients in the PCT group.
OTHERControl
Procalcitonin (PCT) will be measured within 48 hours of admission to the ICU or 48 hours of onset of sepsis (if developed during the ICU stay). In addition, the patients will have daily blood samples taken up to 5 days or until ICU transfer, whichever occurs first.The results of the PCT levels obtained will be blinded and all clinical team members will not be able to access the results.
Sponsors
King Hussein Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Intervention model description
Randomized controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Expected to remain in the ICU for at least 48 hours * Patient meets the SEPSIS-3 criteria for sepsis defined as having a SOFA score change of 2 or more and suspected infection. * Patient on antibiotics for suspected infection
Exclusion criteria
* Patient code is DNR * Patient receiving antibiotics for surgical prophylaxis * Consent cannot be obtained * Patients who are expected to require antibiotics for more than 14 days * Patients who have PCT levels ordered as part of their routine clinical care * Patients who are followed by the Infectious Disease team. * Patient with life expectancy \<24 hours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to antibiotic cessation | 28 days | Time to antibiotic cessation at 28 days, hospital discharge, or death, whichever comes first after randomization |
| Number of antibiotic-free days | 28 days | Number of antibiotic-free days at day 28 after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibiotic utilization | 28 days | The antibiotic utilization will be evaluated by determining the antibiotic daily defined doses (DDD), as set by the World Health Organization, for each patient over the study period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Compliance with the PCT algorithm | 5 days | The clinical decision of the medical team will be compared with the management suggested by the algorithm. |
| Antibiotic de-escalation | 28 days | Determined if de-escalation of antimicrobial therapy is performed during the ICU stay. De-escalation will be defined as reducing both the spectrum of antimicrobial therapy and its potential to promote resistance by driving selective pressure on microbiota. Reducing the number of antibiotics will also be considered as de-escalation. |
| Predictive value of PCT for positive cultures | 28 days | Determined by constructing a receiver operating characteristic (ROC) curve and the area under the ROC curve, as well as the sensitivity, specificity, and cut-off points with the highest predictability. |
| Predictive value of PCT for both mortality | 28 days | Determined by constructing a receiver operating characteristic (ROC) curve and the area under the ROC curve, as well as the sensitivity, specificity, and cut-off points with the highest predictability. |
| Recurrence of infection | 28 days | Defined as a new infection that develops within 48 hours after stopping or de-escalating antibiotics. |
Countries
Jordan
Outcome results
None listed