CEFtolozane-Tazobactam for the Empiric Anti-bacterial Treatment of Neutropenic Fever in Hematology Patients

NCT05061654 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: MRC-02-21-015
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with blood cancers and those who received a bone marrow transplant frequently have low circulating white blood cell countS. Fever in patients with low white blood cell count requires early appropriate antibiotic treatment to prevent complications including death. Bacteria have increasingly become more resistant to existing antibiotic options. Ceftolozane-tazobactam is a newer type of antibiotic that has been shown to be safe and effective in infections caused by several types of resistant bacteria that can cause serious infections in individuals with low blood count. This study aims to examine the effectiveness of this antibiotic in these types of patients. Patients with blood cancer and those who have received a bone transplant will be offered the option to join this study if they develop unexplained fever. If informed consent is granted, they will receive ceftolozane-tazobactam on top of the usual care that such patients receive. The patients will then be followed very closely to check their response to the treatment and if they develop any untoward events. The study will include 164 patients over an estimated 2 year period. The study is funded by Merck \& Co, the company that manufactures the study antibiotic. However, Merck \& Co. will not be involved in the actual running of the study, the collection of the study results or their analysis and interpretation. The study protocol has been reviewed and approved by an independent research oversight committee.

Conditions

Neutropenia, Febrile; Hematologic Cancer

Outcome Measures

Primary Outcomes (1)

• Treatment success without modification of anti-bacterial therapy

  Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis).

  72 hours

Secondary Outcomes (3)

• Treatment success without modification of anti-bacterial therapy

  7 days

• Days to defervescence

  30 days

• 30-day survival

  30 days

Other Outcomes (1)

• In-vitro susceptibility to ceftolozane-tazobactam of any Enterobacterales or P. aeruginosa isolated from the study subjects

  30 days

Study Arms (1)

Treatment arm

EXPERIMENTAL

Eligible patients will be started on empiric ceftolozane-tazobactam in addition to standard care.

Drug: Ceftolozane-tazobactam IV

Interventions

Ceftolozane-tazobactam IV DRUG

Empiric Ceftolozane-tazobactam IV 3g over 1 hour every 8 hours. The dose will be reduced to 1.5g 8 hourly in patients with CrCl of 30-50 ml/min, and to 750mg every 8 hours in those with CrCl of 15-29 ml/min. Patients on hemodialysis will receive 2.25g loading dose followed by 450mg every 8 hours.

Also known as: Zerbaxa

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized with an underlying diagnosis of hematological cancer or receipt of hematopoietic stem cell transplantation.
• Age ≥18 years.
• Absolute neutrophil count (ANC) of \<0.5x10\^9/L or \<1.0x10\^9/L with a predicted decline to \<0.5x10\^9/L within the next 2 days.
• Oral temperature of ≥ 38.3 °C once, ≥ 38.0 °C lasting for at least 1 hour, or ≥ 38.0 °C twice within 12 hours.

You may not qualify if:

• Allergy to cephalosporins.
• Expected survival of ≤72 hours.
• Expected ANC recovery within ≤72 hours.
• Receipt of any antipseudomonal carbapenem therapy within the preceding 14 days.
• Documented current or past infection or colonization with ceftolozane-tazobactam- resistant Enterobacterales or P. aeruginosa.
• Pregnancy.
• Previous enrollment in CEF-10 Study (subjects previously enrolled in this study cannot be enrolled again during subsequent episodes of neutropenic fever).
• Ongoing therapy or planned continuation of therapy outside the National Center for Cancer Care and Research.

Sponsors & Collaborators

• Hamad Medical Corporation: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hamad Medical Corporation, National Center for Cancer Care and Research

Doha, Qatar

Location

MeSH Terms

Conditions

Febrile Neutropenia; Hematologic Neoplasms

Interventions

ceftolozane, tazobactam drug combination

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Neoplasms by Site; Neoplasms

Study Officials

• Ali S. Omrani, FRCP

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be a prospective, non-comparative, single-arm, single center, open-label interventional study.

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: September 29, 2021
• Study Start: August 1, 2022
• Primary Completion: January 1, 2024
• Study Completion: June 1, 2024
• Last Updated: August 14, 2023

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

QA (1)