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Trial record 32 of 257 for:    Anti-Infective Agents AND Antibiotics, Antitubercular AND broad

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

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ClinicalTrials.gov Identifier: NCT03683329
Recruitment Status : Recruiting
First Posted : September 25, 2018
Last Update Posted : February 5, 2019
Sponsor:
Information provided by (Responsible Party):
Institut Paoli-Calmettes

Brief 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.


Condition or disease Intervention/treatment Phase
Critical Care Cancer Other: Antibiotic de-escalation Other: Standard treatment Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 466 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Antibiotic De-escalation in Onco-hematology Patients for Sepsis or Septic Shock
Actual Study Start Date : November 26, 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  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 Outcome Measures :
  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 anfungal de-escalated [ Time Frame: From inclusion to ICU discharge until day 90 ]
    Number of anfungal 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03683329


Contacts
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Contact: GENRE Dominique, MD + 33 4 91 22 37 78 drci.up@ipc.unicancer.fr
Contact: COURNIER Sandra + 33 4 91 22 37 78 drci.up@ipc.unicancer.fr

Locations
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France
GENRE Recruiting
Marseille, France, 13273
Contact: GENRE Dominique, MD    + 33 4 91 22 37 78    drci.up@ipc.unicancer.fr   
Contact: COURNIER Sandra    + 33 4 91 22 37 78    drci.up@ipc.unicancer.fr   
Principal Investigator: Mokart Djamel, MD, PhD         
Sponsors and Collaborators
Institut Paoli-Calmettes
Investigators
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Principal Investigator: MOKART Djamel, MD Institut Paoli-Calmettes

Additional Information:
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Responsible Party: Institut Paoli-Calmettes
ClinicalTrials.gov Identifier: NCT03683329     History of Changes
Other Study ID Numbers: DéPOH-IPC 2015-022
First Posted: September 25, 2018    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut Paoli-Calmettes:
critical care
cancer
antimicrobial treatment
de-escalation
septic shock
sepsis
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Sepsis
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock