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

Pneumonia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04673175
• Other study ID #: 19-11021048
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 20, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Weill Medical College of Cornell University
• Contact: Anna Gwak, BA
• Phone: 2127464089
• Email: ang4021[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 30, 2024
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bacteremia
• Hematologic Malignancy
• Hematologic Neoplasms
• Neoplasms
• Pneumonia
• Pseudomonas Aeruginosa
• Pseudomonas Infections

Intervention

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).

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global response at end of therapy	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."	Day 60
Secondary	Survival at 30 days	Survival will be assessed by chart review or phone visit, as appropriate.	Day 30
Secondary	Survival at 60 days	Survival will be assessed by chart review or phone visit, as appropriate.	Day 60
Secondary	Time in days to resolution of bacteremia	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.	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
Secondary	Time in days of hospital stays	This will be obtained from Hospitalization Status Assessment.	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
Secondary	Time in days of ICU stays	This will be obtained from Hospitalization Status Assessment.	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
Secondary	Time in days to emergence of resistant isolates	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.	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
Secondary	Time in days to appropriate therapy	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.	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
Secondary	Change of microbiological eradication	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.	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
Secondary	Incidence of abnormal and physical examinations findings - general appearance	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - neurological	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - heart/cardiovascular	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - lungs	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - abdomen	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - endocrine	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - extremities	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - lymphatic	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Incidence of abnormal and physical examinations findings - skin	A physical examination assessing and documenting changes from the previous examination, including any new abnormalities, will be conducted.	3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4)
Secondary	Time in days until stabilization or resolution of pneumonic infiltrates	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.	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
Secondary	Time in days to initial antimicrobial therapy	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.	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
Secondary	Change in days until emergence of other bacteria	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.	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
Secondary	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