Phase 3
N=726
Safety and Efficacy Study of Ceftolozane/Tazobactam to Treat Ventilated Nosocomial Pneumonia (MK-7625A-008)
Healthcare-Associated Pneumonia · Ventilator-Associated Pneumonia · Lung Diseases
Bottom Line
View on ClinicalTrials.gov: NCT02070757 ↗Enrolled (actual)
726
Serious AEs
39.0%
Results posted
May 2019
Primary outcome: Primary: Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28 — 24.0; 25.3 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Ceftolozane/tazobactam (Drug); Meropenem (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Primary completion
- May 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28 |
24.0; 25.3 | — |
| SECONDARY Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population |
54.4; 53.3 | — |
| SECONDARY Percentage of Participants With All Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population - Day 28 |
20.1; 25.5 | — |
| SECONDARY Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population |
63.8; 64.7 | — |
| SECONDARY Percentage of Participants With Per-Participant Microbiological Response of Cure or Presumed Cure at the Test-of-Cure (TOC) Visit in the Microbiologically Evaluable (ME) Population |
70.4; 62.7 | — |
| SECONDARY Percentage of Participants With Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the Test-of-Cure (TOC) Visit in the Microbiologically Evaluable (ME) Population (>=10 Isolates at Baseline) |
69.9; 62.4; 79.3; 55.3; 68.7; 65.6 | — |
| SECONDARY Percentage of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population - Day 14 |
14.1; 12.9 | — |
| SECONDARY Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population |
66.0; 66.8 | — |
| SECONDARY Percentage of Participants With Per-Participant Microbiological Response of Cure or Presumed Cure at the End-of-Therapy (EOT) Visit in the Microbiologically Evaluable (ME) Population |
80.9; 78.8 | — |
| SECONDARY Percentage of Participants With Clinical Response of Clinical Cure at the Late Follow-up (LFU) Visit in the Clinically Evaluable (CE) Population |
52.8; 51.6 | — |
| SECONDARY Percentage of Participants Who Report 1 or More Adverse Event (AE) |
85.9; 83.3 | — |
| SECONDARY Percentage of Participants With Any Serious Adverse Event (SAE) |
42.1; 35.9 | — |
| SECONDARY Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE) |
10.2; 11.7 | — |
Summary
This is a phase 3, multicenter, prospective, randomized study of intravenous (IV) ceftolozane/tazobactam versus IV meropenem in the treatment of adult participants with either ventilator-associated bacterial pneumonia (VABP) or ventilated hospital-acquired bacterial pneumonia (HABP). The primary objective is to demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in adult participants with ventilated nosocomial pneumonia (VNP) based on the difference in Day 28 all-cause mortality rates in the Intent-to-treat (ITT) population using a non-inferiority margin of 10%.
Eligibility Criteria
Key Inclusion Criteria
- Adult participants diagnosed with either VABP or ventilated HABP requiring IV antibiotic therapy;
- Intubated and on mechanical ventilation at the time of randomization;
- New or progressive infiltrate on chest radiography consistent with pneumonia;
- Presence of clinical criteria consistent with a diagnosis of ventilated nosocomial pneumonia.
Key Exclusion Criteria
- History of moderate or severe hypersensitivity reactions to beta-lactam antibiotics;
- Prior non-study antibiotics for > 24 hours;
- Gram stain of lower respiratory tract specimen showing only gram positive bacteria;
- Active immunosuppression;
- End-stage renal disease or requirement for dialysis;
- Expected survival < 72 hours;
- Severe confounding respiratory condition (i.e., chest trauma with paradoxical respiration);
- Known or suspected community-acquired bacterial pneumonia.
- Anticipated concomitant use of any of the following medications during the course of study therapy: valproic acid or divalproex sodium. Anticipated concomitant use of serotonin re-uptake inhibitors, tricyclic antidepressants, or serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone during the course of linezolid treatment.
- Receipt of a monoamine oxidase inhibitor within 14 days prior to the first dose of study drug or anticipated concomitant use during the course of linezolid therapy.
Data sourced from ClinicalTrials.gov (NCT02070757). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.