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

Sponsor

Weill Medical College of Cornell University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04673175

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arm

22.4

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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

Actual Study Start Date :

Jul 20, 2022

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

Global response at end of therapy [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

Survival at 30 days [Day 30]
Survival will be assessed by chart review or phone visit, as appropriate.
Survival at 60 days [Day 60]
Survival will be assessed by chart review or phone visit, as appropriate.
Time in days to resolution of bacteremia [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.
Time in days of hospital stays [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.
Time in days of ICU stays [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.
Time in days to emergence of resistant isolates [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.
Time in days to appropriate therapy [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.
Change of microbiological eradication [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.
Incidence of abnormal and physical examinations findings - general appearance [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.
Incidence of abnormal and physical examinations findings - neurological [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.
Incidence of abnormal and physical examinations findings - heart/cardiovascular [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.
Incidence of abnormal and physical examinations findings - lungs [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.
Incidence of abnormal and physical examinations findings - abdomen [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.
Incidence of abnormal and physical examinations findings - endocrine [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.
Incidence of abnormal and physical examinations findings - extremities [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.
Incidence of abnormal and physical examinations findings - lymphatic [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.
Incidence of abnormal and physical examinations findings - skin [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.
Time in days until stabilization or resolution of pneumonic infiltrates [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.
Time in days to initial antimicrobial therapy [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.
Change in days until emergence of other bacteria [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.
Number of days on ventilator, as measured by assessment of clinical status [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]