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Completed

NCT Number: NCT03683329

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

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.

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Key information

Conditions

Critical Care Cancer Infections Inflammation Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Shock Shock, Septic Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Institut Paoli Calmettes

Marseille, 13273, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Age ≥ 18 years,
  • 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
  • Patient treated with an empirical antibiotic treatment,
  • Patient with at least one microbiological sample collected at least within the first 48 hours following the diagnosis of sepsis in ICU
  • Patient with an identified infectious site according to the definitions,
  • Patient with an identified bacteria microorganism after microbiological examination,
  • Patient affiliated to the national French statutory healthcare insurance system or beneficiary of this regimen.

Exclusion criteria

  • Patient colonized with a multi-drug resistant organisms preventing de-escalation antibiotic,
  • Pregnant or breast-feeding woman,
  • No affiliation to the national French statutory healthcare insurance system,
  • Patients deprived of liberty or placed under the authority of a tutor,
  • Inappropriate probabilistic antibiotic treatment,
  • Expected mortality within 48 hours,
  • Patient admitted to the ICU for end-of-life care (do-not-resuscitate patients) . Do-not-intubate (DNI) patients can be included.

Treatment and study plan

Antibiotic de-escalation

Other

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

Other

Antibiotic treatment will be delivered according to current practice, in agreement with the national and international recommendation.

Primary outcomes

  1. Hospital mortality

    Time frame: From day of inclusion until day of ICU discharge, up to 3 months

    death from any cause during hospital stay

Secondary outcomes

  1. Death

    Time frame: From day of inclusion until ICU discharge, day 28 and day 90

    death from any cause into the ICU, day 28 and day 90

  2. ICU length of stay

    Time frame: From day of inclusion until ICU discharge (until day 90)

  3. Hospital length of stay

    Time frame: From day of inclusion until ICU discharge (until day 90)

  4. Severe organ dysfunctions

    Time frame: From day of inclusion until ICU discharge (until day 90)

    A Sepsis-related Organ Failure Assessment (SOFA) score>2 for each organ (respiratory, hematologic, cardiac, neurologic, hepatic, renal)

  5. Respiratory dysfunction-free days at day 28

    Time frame: from inclusion to day 28

    days without respiratory dysfunction (respiratory SOFA score<3)

  6. Renal dysfunction-free days at day 28

    Time frame: from inclusion to day 28

    days without renal dysfunction (renal SOFA score<3)

  7. Neurologic dysfunction-free days at day 28

    Time frame: from inclusion to day 28

    days without neurologic dysfunction (neurologic SOFA score<3)

  8. Cardiac dysfunction-free days at day 28

    Time frame: from inclusion to day 28

    days without cardiac dysfunction (cardiac SOFA score<3)

  9. Hepatic dysfunction-free days at day 28

    Time frame: From inclusion to day 28

    days without hepatic dysfunction (hepatic SOFA score<3)

  10. Hematologic dysfunction-free days at day 28

    Time frame: From inclusion to day 28

    days without hematologic dysfunction (hematologic SOFA score<3)

  11. Ventilator-free days at day 28

    Time frame: From inclusion to day 28

    days without invasive mechanical ventilation

  12. Vasopressors-free days at day 28

    Time frame: From inclusion to day 28

    days without vasopressors treatment

  13. Dialysis-free days at day 28

    Time frame: From inclusion to day 28

    days without dialysis treatment

  14. Duration of antibiotic treatment during ICU stay

    Time frame: From day of admission to ICU until day 90

    Duration between the first antibiotic initiation and the last antibiotic stop

  15. Number of antibiotics de-escalated

    Time frame: From inclusion to ICU discharge until day 90

    Number of antibiotics de-escalated in each arm

  16. Number of antifungal de-escalated

    Time frame: From inclusion to ICU discharge until day 90

    Number of antifungal de-escalated in each arm

  17. Number of antiviral de-escalated

    Time frame: From inclusion to ICU discharge until day 90

    Number of antiviral de-escalated in each arm

  18. Antibiotic-free days at day 28

    Time frame: From inclusion to day 28

    days without antibiotic treatment

  19. Antibiotic-free days during ICU stay

    Time frame: From admission to ICU to ICU discharge until day 90

    days without antibiotic treatment

  20. Antibiotic-free days during hospital stay

    Time frame: From admission to ICU to hospital discharge until day 90

    Days without antibiotic treatment

  21. Antibiotic-free days at day 90

    Time frame: From admission to ICU to day 90

    Days without antibiotic treatment

  22. Antifungal-free days at day 28

    Time frame: From admission to ICU to day 28

    Days without antifungal treatment

  23. Antiviral-free days at day 28

    Time frame: From admission to ICU to day 28

    Days without antiviral treatment

  24. Antifungal-free days during ICU stay

    Time frame: From admission to ICU to ICU discharge until day 90

    Days without antifungal treatment

  25. Antiviral-free days during ICU stay

    Time frame: From admission to ICU to ICU discharge until day 90

    Days without antiviral treatment

  26. Antiviral-free days during hospital stay

    Time frame: From admission to ICU to hospital discharge until day 90

    Days without antiviral treatment

  27. Antifungal-free days during hospital stay

    Time frame: From admission to ICU to hospital discharge until day 90

    Days without antifungal treatment

  28. Antifungal-free days at day 90

    Time frame: From admission to ICU to day 90

    Days without antifungal treatment

  29. Antiviral-free days at day 90

    Time frame: From admission to ICU to day 90

    Days without antiviral treatment

  30. Number of days of exposure to each antibiotic per 1000 inpatient days

    Time frame: From admission to ICU to ICU discharge until day 90

    For the entire cohort:(number of antibiotic days / number of ICU days)*1000

  31. Number of days of exposure to each antifungal per 1000 inpatient days

    Time frame: From admission to ICU to ICU discharge until day 90

    For the entire cohort:(number of antifungal days / number of ICU days)*1000

  32. Number of days of exposure to each antiviral per 1000 inpatient days

    Time frame: From admission to ICU to ICU discharge until day 90

    For the entire cohort:(number of antiviral days / number of ICU days)*1000

  33. Adverse events

    Time frame: From inclusion to ICU discharge until day 90

    Adverse events assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0

  34. Compliance to de-escalation strategy

    Time frame: From inclusion to ICU discharge until day 90

    number of patients de-escalated/number of patients included in the experimental arm

  35. Compliance to the continuation strategy

    Time frame: From inclusion to ICU discharge until day 90

    number of patients not de-escalated/number of patients included in the continuation group

  36. Percentage of emerging multidrug-resistant bacteria

    Time frame: From inclusion until day 28

    Percentage of emerging multidrug-resistant bacteria isolated from specimen taken for routine microbiological assessments

  37. Cost of antibiotic treatment

    Time frame: From inclusion to ICU discharge until day 90

  38. Patients presenting with bacterial pneumoniae,

    Time frame: From inclusion to ICU discharge until day 90

  39. Patients presenting with Intra-abdominal infection.

    Time frame: From inclusion to ICU discharge until day 90

  40. Patients presenting with bacteraemia

    Time frame: From inclusion to ICU discharge until day 90

  41. Number of patients in the de-escalation group without de-escalation

    Time frame: From inclusion to ICU discharge until day 90

  42. Rate of new infectious episode requiring a new antibiotic treatment

    Time frame: From inclusion to ICU discharge until day 90

  43. Rate of patients requiring an escalation after de-escalation

    Time frame: From inclusion to ICU discharge until day 90

  44. Rate of recovery from infection

    Time frame: From inclusion to ICU discharge until day 90

Sponsors and collaborators

Lead sponsor

Institut Paoli-Calmettes

Other

Registry information

Acronym: DéPOH

Important dates

Study start
2018
Primary completion
2024
Study completion
2024
First posted
Sep 25, 2018
Registry last updated
Feb 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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