Clinical trial NCT04673175: Ceftolozane-Tazobactam for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pseudomonas Aeruginosa
Pneumonia
Hematologic Malignancy
Keywords: Pseudomonas Aeruginosa
Pneumonia
Hematologic Malignancy
Ceftolozane-Tazobactam
Zerbaxa
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-12-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* At least 18 years old
* Presence of hematologic malignancy or Hematopoietic Stem Cell Transplantation
* Identification of Pseudomonas aeruginosa by rapid molecular diagnostic assay from a blood culture or from a respiratory sample in the setting of radiologically documented pneumonia and clinical symptoms compatible with pneumonia.

Exclusion Criteria:

* Anaphylactic hypersensitivity or allergic reaction to cephalosporins
* Participants with expected mortality within 48 hours
* Hemodialysis or continuous renal replacement therapy, or creatinine clearance \<15 ml/min
* Prior non-study anti-pseudomonal therapy for \>72 hours
* History of a strain of Pseudomonas aeruginosa with MIC \>4 microgram/ml to ceftolozane/tazobactam
* Polymicrobial aerobic Gram-negative infection as determined by ID research team

Patients who completed this study and subsequently experience a separate, recurrent Pseudomonas aeruginosa infection, may be re-enrolled into this study if all eligibility criteria are met.

Primary outcomes:
measure: Global response at end of therapy
timeFrame: Day 60
Secondary outcomes:
measure: Survival at 30 days
timeFrame: Day 30
measure: Survival at 60 days
timeFrame: Day 60
measure: Time in days to resolution of bacteremia
timeFrame: 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
measure: Time in days of hospital stays
timeFrame: 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
measure: Time in days of ICU stays
timeFrame: 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
measure: Time in days to emergence of resistant isolates
timeFrame: 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
measure: Time in days to appropriate therapy
timeFrame: 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
measure: Change of microbiological eradication
timeFrame: 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
measure: Incidence of abnormal and physical examinations findings - general appearance
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - neurological
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - heart/cardiovascular
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - lungs
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - abdomen
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - endocrine
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - extremities
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - lymphatic
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Incidence of abnormal and physical examinations findings - skin
timeFrame: 3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
measure: Time in days until stabilization or resolution of pneumonic infiltrates
timeFrame: 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
measure: Time in days to initial antimicrobial therapy
timeFrame: 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
measure: Change in days until emergence of other bacteria
timeFrame: 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
measure: Number of days on ventilator, as measured by assessment of clinical status
timeFrame: 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
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Markus Plate, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Satlin MJ, Walsh TJ. Multidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2017 Dec;19(6):10.1111/tid.12762. doi: 10.1111/tid.12762. Epub 2017 Oct 25.
citation: Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073.
citation: Nguyen L, Garcia J, Gruenberg K, MacDougall C. Multidrug-Resistant Pseudomonas Infections: Hard to Treat, But Hope on the Horizon? Curr Infect Dis Rep. 2018 Jun 6;20(8):23. doi: 10.1007/s11908-018-0629-6.
citation: Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy. 2015 Oct;35(10):949-62. doi: 10.1002/phar.1636.
citation: Munita JM, Aitken SL, Miller WR, Perez F, Rosa R, Shimose LA, Lichtenberger PN, Abbo LM, Jain R, Nigo M, Wanger A, Araos R, Tran TT, Adachi J, Rakita R, Shelburne S, Bonomo RA, Arias CA. Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa. Clin Infect Dis. 2017 Jul 1;65(1):158-161. doi: 10.1093/cid/cix014.
citation: Gallagher JC, Satlin MJ, Elabor A, Saraiya N, McCreary EK, Molnar E, El-Beyrouty C, Jones BM, Dixit D, Heil EL, Claeys KC, Hiles J, Vyas NM, Bland CM, Suh J, Biason K, McCoy D, King MA, Richards L, Harrington N, Guo Y, Chaudhry S, Lu X, Yu D. Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: A Multicenter Study. Open Forum Infect Dis. 2018 Oct 31;5(11):ofy280. doi: 10.1093/ofid/ofy280. eCollection 2018 Nov.
citation: Petraitis V, Petraitiene R, Naing E, Aung T, Thi WP, Kavaliauskas P, Win Maung BB, Michel AO, Ricart Arbona RJ, DeRyke AC, Culshaw DL, Nicolau DP, Satlin MJ, Walsh TJ. Ceftolozane-Tazobactam in the Treatment of Experimental Pseudomonas aeruginosa Pneumonia in Persistently Neutropenic Rabbits: Impact on Strains with Genetically Defined Mechanisms of Resistance. Antimicrob Agents Chemother. 2019 Aug 23;63(9):e00344-19. doi: 10.1128/AAC.00344-19. Print 2019 Sep.