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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Critical Care
• Intervention / Treatment: Other: Antibiotic de-escalation; Other: Standard treatment

Detailed Description

An interim analysis planned after inclusion of 233 patients.

* Subgroup analyses will be performed on patient subsets:

• Patients with allogeneic hematopoietic stem cell transplant,
• 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.

• Study Type: Interventional
• Enrollment (Actual): 398
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13273
    • Institut Paoli Calmettes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antibiotic de-escalation; According to the results of the antibiogram of the suspected causative bacteria, the ''pivotal'' antibiotic (antipseudomonal betalactam) used for empirical treatment is switched to an antibiotic with a spectrum as narrow as possible according to the targeted pathogens,; Stop the companion antibiotic (aminoglycoside, fluoroquinolone, macrolide) between day 2 and day 3 of antibiotic treatment as much as possible,; Stop the empirical antibiotic directed against methicillin-resistant staphylococcus aureus (MRSA) or an enterococcus in the absence of these bacteria in the culture.	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.
Active Comparator: Standard treatment without de-escalation; The companion antibiotic is stopped between day 3 and day 5 of antibiotic treatment as much as possible and according to the local prescription,; Empirical antibiotics directed against MRSA or enterococcus were used according to local prescription and/or international guidelines,; The pivotal antibiotic of the empirical treatment is continued for the entire duration of the treatment, independently of microbiological results. For prolonged treatment, the physician has the choice of de-escalating after 8-15 days of treatment.	Other: Standard treatment; Antibiotic treatment will be delivered according to current practice, in agreement with the national and international recommendation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital mortality	death from any cause during hospital stay	From day of inclusion until day of ICU discharge, up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
ICU length of stay		From day of inclusion until ICU discharge (until day 90)
Hospital length of stay		From day of inclusion until ICU discharge (until day 90)
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)
Respiratory dysfunction-free days at day 28	days without respiratory dysfunction (respiratory SOFA score<3)	from inclusion to day 28
Renal dysfunction-free days at day 28	days without renal dysfunction (renal SOFA score<3)	from inclusion to day 28
Neurologic dysfunction-free days at day 28	days without neurologic dysfunction (neurologic SOFA score<3)	from inclusion to day 28
Cardiac dysfunction-free days at day 28	days without cardiac dysfunction (cardiac SOFA score<3)	from inclusion to day 28
Hepatic dysfunction-free days at day 28	days without hepatic dysfunction (hepatic SOFA score<3)	From inclusion to day 28
Hematologic dysfunction-free days at day 28	days without hematologic dysfunction (hematologic SOFA score<3)	From inclusion to day 28
Ventilator-free days at day 28	days without invasive mechanical ventilation	From inclusion to day 28
Vasopressors-free days at day 28	days without vasopressors treatment	From inclusion to day 28
Dialysis-free days at day 28	days without dialysis treatment	From inclusion to day 28
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
Number of antibiotics de-escalated	Number of antibiotics de-escalated in each arm	From inclusion to ICU discharge until day 90
Number of antiviral de-escalated	Number of antiviral de-escalated in each arm	From inclusion to ICU discharge until day 90
Antibiotic-free days at day 28	days without antibiotic treatment	From inclusion to day 28
Antibiotic-free days during ICU stay	days without antibiotic treatment	From admission to ICU to ICU discharge until day 90
Antibiotic-free days during hospital stay	Days without antibiotic treatment	From admission to ICU to hospital discharge until day 90
Antibiotic-free days at day 90	Days without antibiotic treatment	From admission to ICU to day 90
Antifungal-free days at day 28	Days without antifungal treatment	From admission to ICU to day 28
Antiviral-free days at day 28	Days without antiviral treatment	From admission to ICU to day 28
Antifungal-free days during ICU stay	Days without antifungal treatment	From admission to ICU to ICU discharge until day 90
Antiviral-free days during ICU stay	Days without antiviral treatment	From admission to ICU to ICU discharge until day 90
Antiviral-free days during hospital stay	Days without antiviral treatment	From admission to ICU to hospital discharge until day 90
Antifungal-free days during hospital stay	Days without antifungal treatment	From admission to ICU to hospital discharge until day 90
Antifungal-free days at day 90	Days without antifungal treatment	From admission to ICU to day 90
Antiviral-free days at day 90	Days without antiviral treatment	From admission to ICU to day 90
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
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
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
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
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
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
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
Cost of antibiotic treatment		From inclusion to ICU discharge until day 90
Patients presenting with bacterial pneumoniae,		From inclusion to ICU discharge until day 90
Patients presenting with Intra-abdominal infection.		From inclusion to ICU discharge until day 90
Patients presenting with bacteraemia		From inclusion to ICU discharge until day 90
Number of patients in the de-escalation group without de-escalation		From inclusion to ICU discharge until day 90
Rate of new infectious episode requiring a new antibiotic treatment		From inclusion to ICU discharge until day 90
Rate of patients requiring an escalation after de-escalation		From inclusion to ICU discharge until day 90
Rate of recovery from infection		From inclusion to ICU discharge until day 90
Number of antifungal de-escalated	Number of antifungal de-escalated in each arm	From inclusion to ICU discharge until day 90

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes
• Investigators: Principal Investigator: MOKART Djamel, MD, Institut Paoli-Calmettes

Publications and helpful links

Helpful Links

• Institut Paoli-Calmettes

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Actual): July 26, 2024
• Study Completion (Actual): July 26, 2024

Study Registration Dates

• First Submitted: August 12, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: septic shock; critical care; cancer; sepsis; de-escalation; antimicrobial treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Neoplasms; Sepsis; Shock, Septic; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: DéPOH-IPC 2015-022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No