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Ceftolozane-Tazobactam for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation

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ClinicalTrials.gov Identifier: NCT04673175
Recruitment Status : Suspended (Voluntary global product recall of Zerbaxa (ceftolozane and tazobactam) for injection (1.5g).)
First Posted : December 17, 2020
Last Update Posted : January 27, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
This is an open-label study, where participants will be given ceftolozane-tazobactam as the primary treatment for Pseudomonas aeruginosa infections. Open-label means both the investigator and the participant will known what drug will be given. Participants will be followed for approximately 60 days. Ceftolozane-tazobactam is approved by the Food and Drug Administration (FDA) for treatment of serious bacterial infection and the investigator hypothesizes that ceftolozane/tazobactam may be effective as the primary antibiotic treatment for Pseudomonas aeruginosa infections.

Condition or disease Intervention/treatment Phase
Pseudomonas Aeruginosa Pneumonia Hematologic Malignancy Drug: Ceftolozane / Tazobactam Injection Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Ceftolozane-Tazobactam in Conjunction With Rapid Molecular Diagnosis for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Ceftolozane-Tazobactam
Participants receive ceftolozane-tazobactam by injection directly into the vein (intravenously, IV) every 8 hours for 10-14 days.
Drug: Ceftolozane / Tazobactam Injection
Zerbaxa (ceftolozane/tazobactam) for injection is supplied as a white to yellow sterile powder for reconstitution in single-use vials; each vial contains 1 g ceftolozane (equivalent to 1.147 g of ceftolozane sulfate) and 0.5 g tazobactam (equivalent to 0.537 g of tazobactam sodium).




Primary Outcome Measures :
  1. Global response at end of therapy [ Time Frame: Day 60 ]
    The proportion of subjects with a complete or partial Global Response (GR). Complete response is defined as "Survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease and radiological abnormalities, and microbiological evidence of eradication of disease." Partial response is defined as "Survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease and radiological abnormalities, and evidence of clearance of cultures."


Secondary Outcome Measures :
  1. Survival at 30 days [ Time Frame: Day 30 ]
    Survival will be assessed by chart review or phone visit, as appropriate.

  2. Survival at 60 days [ Time Frame: Day 60 ]
    Survival will be assessed by chart review or phone visit, as appropriate.

  3. Time in days to resolution of bacteremia [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 ]
    This will be measured in days from the Subject's initial Pseudomonas aeruginosa blood culture, until the subject has two consecutive negative blood cultures for Pseudomonas aeruginosa , assessed by examining results from daily blood cultures obtained as standard of care.

  4. Time in days of hospital stays [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 ]
    This will be obtained from Hospitalization Status Assessment.

  5. Time in days of ICU stays [ Time Frame: Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 ]
    This will be obtained from Hospitalization Status Assessment.

  6. Time in days to emergence of resistant isolates [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 ]
    This will be measured in days from the most recent microbiological isolate susceptibility testing to ceftolozane/tazobactam showing no resistance, to the first identification of resistance to ceftolozane/tazobactam.

  7. Time in days to appropriate therapy [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 ]
    This will be measured in days from initial treatment for Pseudomonas aeruginosa infection until the Subject begins therapy for this infection that is efficacious, based on microbiologic isolate susceptibility testing and review of Subject's concomitant medications.

  8. Change of microbiological eradication [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 ]
    Microbiological eradication will be defined by resolution of positive blood cultures, by repeat assessment of bronchoalveolar lavage, or in the absence of repeat respiratory tract specimen.

  9. Incidence of abnormal and physical examinations findings - general appearance [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  10. Incidence of abnormal and physical examinations findings - neurological [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  11. Incidence of abnormal and physical examinations findings - heart/cardiovascular [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  12. Incidence of abnormal and physical examinations findings - lungs [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  13. Incidence of abnormal and physical examinations findings - abdomen [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  14. Incidence of abnormal and physical examinations findings - endocrine [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  15. Incidence of abnormal and physical examinations findings - extremities [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  16. Incidence of abnormal and physical examinations findings - lymphatic [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  17. Incidence of abnormal and physical examinations findings - skin [ Time Frame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4) ]
    A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.

  18. Time in days until stabilization or resolution of pneumonic infiltrates [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 ]
    This will be measured in days from Subject's initial presentation of pneumonic infiltrates until Subject's pneumonic infiltrates stabilize or resolve, based on diagnostic imaging obtained as standard of care.

  19. Time in days to initial antimicrobial therapy [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60 ]
    This will be measured in days from initial diagnosis of Pseudomonas aeruginosa infection unit initiation of antimicrobial therapy for this infection, based on review of Subject's concomitant medications.

  20. Change in days until emergence of other bacteria [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 ]
    This will be measured in days from initial diagnosis of Pseudomonas aeruginosa infection until identification of additional bacteria, assessed by examining results from daily blood cultures obtained as standard of care.

  21. Number of days on ventilator, as measured by assessment of clinical status [ Time Frame: Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28 ]


Information from the National Library of Medicine

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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:

  • At least 18 years old
  • Presence of hematologic malignancy or Hematopoietic Stem Cell Transplantation

Exclusion Criteria:

  • Under the age of 18 years old
  • Anaphylactic hypersensitivity or allergic reaction to cephalosporins
  • Participants with expected mortality within 48 hours
  • Hemodialysis or continuous renal replacement therapy

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): NCT04673175


Locations
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United States, New York
Weill Cornell Medicine
New York, New York, United States, 10065
Sponsors and Collaborators
Weill Medical College of Cornell University
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Thomas Walsh, MD Weill Cornell Medicine
Publications:

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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT04673175    
Other Study ID Numbers: 19-11021048
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Weill Medical College of Cornell University:
Pseudomonas Aeruginosa
Pneumonia
Hematologic Malignancy
Ceftolozane-Tazobactam
Zerbaxa
Additional relevant MeSH terms:
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Bacteremia
Pseudomonas Infections
Neoplasms
Hematologic Neoplasms
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Neoplasms by Site
Hematologic Diseases
Bacterial Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Gram-Negative Bacterial Infections
Tazobactam
Ceftolozane
Ceftolozane, tazobactam drug combination
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents