Cefepime-taniborbactam vs Meropenem in Adults With VABP or Ventilated HABP

Study Overview
=================
Brief Summary
-----------------
This is a Phase 3, randomized, multicenter, double-blind, non-inferiority study to evaluate the efficacy and safety of cefepime-taniborbactam compared to meropenem in patients ≥ 18 years of age with ventilated HABP or VABP.

Official Title
-----------------
A Phase 3 Study to Evaluate Cefepime-taniborbactam Compared to Meropenem in Adults With Ventilator Associated Bacterial Pneumonia (VABP) or Ventilated Hospital Acquired Bacterial Pneumonia (vHABP)

Conditions
-----------------
Ventilator-associated Pneumonia, Hospital-acquired Pneumonia

Intervention / Treatment
-----------------
* Drug: Cefepime-taniborbactam
* Drug: Meropenem


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, ≥18 years of age. The patient or patient's legally authorized/acceptable representative (LAR) has voluntarily signed and dated the IRB/IEC approved ICF Meets the clinical diagnosis of ventilated HABP or VABP Have at least one of the following clinical criteria: New onset or worsening of pulmonary symptoms and signs New onset or worsening of purulent respiratory secretions Hypoxemia Need for acute changes in ventilator support Have at least one of the following clinical criteria: Documented fever (defined as body temperature ≥ 38°C [100.4°F] Hypothermia (defined as body temperature ≤ 35°C [95°F]) White blood cell (WBC) ≥10,000 cells/mm3 or ≤4,500 cells/mm3 >15% immature neutrophils (bands). Have new or worsening infiltrate on a pulmonary imaging study that is consistent with bacterial pneumonia within 48 hours prior to randomization. Have a lower respiratory tract specimen sent for Gram stain and quantitative culture within 36 hours prior to the first dose of study drug. Exclusion Criteria: Receipt of effective antibacterial treatment for pneumonia for a continuous duration of >24 hours during the previous 72 hours prior to randomization. Pneumonia known or suspected to be caused by: A bacterial pathogen resistant to meropenem, as assessed by susceptibility testing or against which either one or both study drugs lack activity Viruses, atypical bacteria, or fungi Use of non-study systemic gram-negative therapy. Confounding respiratory conditions. Receiving extracorporeal membrane oxygenation (ECMO). Patients with refractory septic shock. Active immunosuppression. Has a history of serious hypersensitivity (e.g., anaphylaxis), serious allergy, or any serious reaction to cephalosporin, penicillin, carbapenem, or other β-lactam antibiotics. Female patients who are pregnant. Patients with eGFR <10 mL/min/1.73 m2 or are receiving or starting renal replacement therapy or expected to require renal replacement therapy during the treatment phase of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will randomize approximately 316 patients with vHABP or VABP into 2 groups in a 1:1 ratio (158 patients to cefepime-taniborbactam; 158 patients to meropenem).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cefepime-taniborbactam<br>cefepime-taniborbactam (2g/0.5g) IV every 8 hours. | Drug: Cefepime-taniborbactam<br>* Cefepime-taniborbactam administered 2.5g q8h intravenously (IV) over a 4-hour period for 7 days to 14 days at the investigator's discretion. Dose adjustments for renal function may apply.<br>|
| Active Comparator: Meropenem<br>Comparator: meropenem (2g) IV every 8 hours. | Drug: Meropenem<br>* Meropenem will be administered 2g q8h IV over 4 hours for 7 days to 14 days at the investigator's discretion. Dose adjustments for renal function may apply.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACM through Study Day 14 | The primary endpoint is ACM, a binary variable, through Study Day 14. The primary endpoint is evaluated in the ITT population and is based on the patient's survival status through Study Day 14. | Evaluated on Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACM through Study Day 28 | ACM through Study Day 28; analyzed in ITT and MITT analysis populations. | Evaluated on Day 29-33 | 
| Safety Outcomes | Safety assessments include the incidence of TEAEs and SAEs, and discontinuation of study drug due to TEAEs. | From first dose up to Day 33 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ventilated Pneumonia, Hospital Acquired Pneumonia, Bacterial Pneumonia, VABP, vHABP