Antibiotic De-escalation in Onco-hematology Patients for Sepsis or Septic Shock

Cancer Clinical Trial

— DéPOH  

Official title:

Antibiotic De-escalation in Onco-hematology Patients for Sepsis or Septic Shock

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03683329
• Other study ID #: DéPOH-IPC 2015-022
• Status: Recruiting
• Phase: Phase 3
• Start date: November 26, 2018
• Est. completion date: April 2023

Study information

• Verified date: May 2021
• Source: Institut Paoli-Calmettes
• Contact: GENRE Dominique, MD
• Phone: + 33 4 91 22 37 78
• Email: drci.up[@]ipc.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

De-escalation aims at reducing the use of broad-spectrum antibiotics and therefore the emergence of multidrug-resistant (MDR) pathogens. Observational studies suggested that this strategy seems to be safe. However, there is no adequate, direct evidence showing de-escalation of antimicrobial agents to be effective and safe for onco-hematology patients with sepsis or septic shock. Thus, randomized clinical trials are needed for testing the safety and efficiency of de-escalation of antimicrobial therapy. The investigator's hypothesis is that de-escalation of empirical antimicrobial therapy in onco-hematology patients with sepsis or septic shock is noninferior to the continuation of empirical antimicrobial therapy. The first aim of the study is to demonstrate that de-escalation is noninferior to the continuation of broad-spectrum antibiotics in terms of hospital mortality. The secondary aims are to compare the two strategies in terms of mortality, duration of antimicrobial therapy, durations of mechanical ventilation, vasopressor use, numbers of superinfections, organ failure. Antimicrobial de-escalation (ADE) of antimicrobial therapy is a strategy proposed to allow for the rational use of broad-spectrum antimicrobial therapy as the empiric treatment for infections and minimize the overall exposure to these broad-spectrum agents. The need for prompt, effective antimicrobial therapy for patients with known or suspected infections is widely accepted. This principle leads to the use of very broad-spectrum antimicrobial therapy to increase the odds that all suspected potential pathogens are adequately treated. However, the potential drawback is selection of multidrug-resistant (MDR) organisms. ADE is widely recommended in the management of antimicrobial therapy in intensive care unit (ICU) patients. The Surviving Sepsis Campaign guidelines describe and recommend the process for selecting antimicrobial therapy as commencement of antimicrobials within the first hour, antimicrobial therapy broad enough to cover all likely pathogens, and daily reassessment for potential ADE. To date, no randomized study assessing this strategy is available for this specific population of cancer critically ill patients. In a recent systematic review based on 13 observational studies and one randomized controlled trial, the authors conclude that the equipoise remains and a large randomized trial is required to assess the effect of the antibiotics de-escalation strategy on the bacterial ecosystem, on MDR carriage, and on patient outcomes.

Description:

An interim analysis planned after inclusion of 233 patients. * Subgroup analyses will be performed on patient subsets: - Patients with allogeneic HCST, - Neutropenic patients (Neutrophils < 0.5 Giga/L), - Hematological disease, - Oncological disease, - Polymicrobial sepsis, - Multi-drug resistant organisms, - Patients presenting with bacterial pneumoniae, - Patients presenting with Intra-abdominal infection, - Patients presenting with bacteraemia, - Patients presenting with gram negative bacteria infection, - Patients presenting with gram positive cocci infection, - Patients presenting with septic shock, - Patients presenting with sepsis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 466
• Est. completion date: April 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent from the patient or proxy (if present) before inclusion or once possible when patient has been included in a context of emergency

2. Age = 18 years,

3. Onco-hematology patient admitted to intensive care for sepsis or septic shock

according to the following criteria:

• Sepsis:
• A suspected infection
• And an acute increase of = 2 SOFA points (a proxy for organ dysfunction)
• Septic shock:
• sepsis
• and vasopressor therapy needed to elevate MAP =65 mm Hg and lactate >2 mmol/L despite adequate fluid resuscitation

4. Patient treated with an empirical antibiotic treatment,

5. Patient with at least one microbiological sample collected at least within the first 48 hours following the diagnosis of sepsis in ICU

6. Patient with an identified infectious site according to the definitions,

7. Patient with an identified bacteria microorganism after microbiological examination,

8. Patient affiliated to the national French statutory healthcare insurance system or beneficiary of this regimen.

Exclusion Criteria:

1. Patient colonized with a multi-drug resistant organisms preventing de-escalation antibiotic,

2. Pregnant or breast-feeding woman,

3. No affiliation to the national French statutory healthcare insurance system,

4. Patients deprived of liberty or placed under the authority of a tutor,

5. Inappropriate probabilistic antibiotic treatment,

6. Expected mortality within 48 hours,

7. Patient admitted to the ICU for end-of-life care (do-not-resuscitate patients) . Do-not-intubate (DNI) patients can be included.

Related Conditions & MeSH terms

• Cancer
• Critical Care
• Sepsis
• Shock, Septic

Intervention

Other:
• Antibiotic de-escalation
All the therapeutic protocols made the object of a consensus between the different partners of the study. Antibiotic treatment will be delivered according to current practice, in agreement with the national and international recommendation.
• Standard treatment
Antibiotic treatment will be delivered according to current practice, in agreement with the national and international recommendation.

Locations

Country	Name	City	State
France	GENRE	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Institut Paoli-Calmettes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hospital mortality	death from any cause during hospital stay	From day of inclusion until day of ICU discharge, up to 3 months
Secondary	Death	death from any cause into the ICU, day 28 and day 90	From day of inclusion until ICU discharge, day 28 and day 90
Secondary	ICU length of stay		From day of inclusion until ICU discharge (until day 90)
Secondary	Hospital length of stay		From day of inclusion until ICU discharge (until day 90)
Secondary	Severe organ dysfunctions	A Sepsis-related Organ Failure Assessment (SOFA) score>2 for each organ (respiratory, hematologic, cardiac, neurologic, hepatic, renal)	From day of inclusion until ICU discharge (until day 90)
Secondary	Respiratory dysfunction-free days at day 28	days without respiratory dysfunction (respiratory SOFA score<3)	from inclusion to day 28
Secondary	Renal dysfunction-free days at day 28	days without renal dysfunction (renal SOFA score<3)	from inclusion to day 28
Secondary	Neurologic dysfunction-free days at day 28	days without neurologic dysfunction (neurologic SOFA score<3)	from inclusion to day 28
Secondary	Cardiac dysfunction-free days at day 28	days without cardiac dysfunction (cardiac SOFA score<3)	from inclusion to day 28
Secondary	Hepatic dysfunction-free days at day 28	days without hepatic dysfunction (hepatic SOFA score<3)	From inclusion to day 28
Secondary	Hematologic dysfunction-free days at day 28	days without hematologic dysfunction (hematologic SOFA score<3)	From inclusion to day 28
Secondary	Ventilator-free days at day 28	days without invasive mechanical ventilation	From inclusion to day 28
Secondary	Vasopressors-free days at day 28	days without vasopressors treatment	From inclusion to day 28
Secondary	Dialysis-free days at day 28	days without dialysis treatment	From inclusion to day 28
Secondary	Duration of antibiotic treatment during ICU stay	Duration between the first antibiotic initiation and the last antibiotic stop	From day of admission to ICU until day 90
Secondary	Number of antibiotics de-escalated	Number of antibiotics de-escalated in each arm	From inclusion to ICU discharge until day 90
Secondary	Number of anfungal de-escalated	Number of anfungal de-escalated in each arm	From inclusion to ICU discharge until day 90
Secondary	Number of antiviral de-escalated	Number of antiviral de-escalated in each arm	From inclusion to ICU discharge until day 90
Secondary	Antibiotic-free days at day 28	days without antibiotic treatment	From inclusion to day 28
Secondary	Antibiotic-free days during ICU stay	days without antibiotic treatment	From admission to ICU to ICU discharge until day 90
Secondary	Antibiotic-free days during hospital stay	Days without antibiotic treatment	From admission to ICU to hospital discharge until day 90
Secondary	Antibiotic-free days at day 90	Days without antibiotic treatment	From admission to ICU to day 90
Secondary	Antifungal-free days at day 28	Days without antifungal treatment	From admission to ICU to day 28
Secondary	Antiviral-free days at day 28	Days without antiviral treatment	From admission to ICU to day 28
Secondary	Antifungal-free days during ICU stay	Days without antifungal treatment	From admission to ICU to ICU discharge until day 90
Secondary	Antiviral-free days during ICU stay	Days without antiviral treatment	From admission to ICU to ICU discharge until day 90
Secondary	Antiviral-free days during hospital stay	Days without antiviral treatment	From admission to ICU to hospital discharge until day 90
Secondary	Antifungal-free days during hospital stay	Days without antifungal treatment	From admission to ICU to hospital discharge until day 90
Secondary	Antifungal-free days at day 90	Days without antifungal treatment	From admission to ICU to day 90
Secondary	Antiviral-free days at day 90	Days without antiviral treatment	From admission to ICU to day 90
Secondary	Number of days of exposure to each antibiotic per 1000 inpatient days	For the entire cohort:(number of antibiotic days / number of ICU days)*1000	From admission to ICU to ICU discharge until day 90
Secondary	Number of days of exposure to each antifungal per 1000 inpatient days	For the entire cohort:(number of antifungal days / number of ICU days)*1000	From admission to ICU to ICU discharge until day 90
Secondary	Number of days of exposure to each antiviral per 1000 inpatient days	For the entire cohort:(number of antiviral days / number of ICU days)*1000	From admission to ICU to ICU discharge until day 90
Secondary	Adverse events	Adverse events assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0	From inclusion to ICU discharge until day 90
Secondary	Compliance to de-escalation strategy	number of patients de-escalated/number of patients included in the experimental arm	From inclusion to ICU discharge until day 90
Secondary	Compliance to the continuation strategy	number of patients not de-escalated/number of patients included in the continuation group	From inclusion to ICU discharge until day 90
Secondary	Percentage of emerging multidrug-resistant bacteria	Percentage of emerging multidrug-resistant bacteria isolated from specimen taken for routine microbiological assessments	From inclusion until day 28
Secondary	Cost of antibiotic treatment		From inclusion to ICU discharge until day 90
Secondary	Patients presenting with bacterial pneumoniae,		From inclusion to ICU discharge until day 90
Secondary	Patients presenting with Intra-abdominal infection.		From inclusion to ICU discharge until day 90
Secondary	Patients presenting with bacteraemia		From inclusion to ICU discharge until day 90
Secondary	Number of patients in the de-escalation group without de-escalation		From inclusion to ICU discharge until day 90
Secondary	Rate of new infectious episode requiring a new antibiotic treatment		From inclusion to ICU discharge until day 90
Secondary	Rate of patients requiring an escalation after de-escalation		From inclusion to ICU discharge until day 90
Secondary	Rate of recovery from infection		From inclusion to ICU discharge until day 90

External Links

•   Institut Paoli-Calmettes