Safety and Efficacy Study of Ceftolozane/Tazobactam to Treat Ventilated Nosocomial Pneumonia (MK-7625A-008) (ASPECT-NP)

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Status and phase: Completed; Phase 3

Conditions: Ventilator-Associated Pneumonia; Lung Diseases; Healthcare-Associated Pneumonia

Treatments: Drug: Meropenem; Drug: Ceftolozane/tazobactam

Study type: Interventional

Funder types: Industry

Identifiers

NCT02070757

MK-7625A-008 (Other Identifier)

163338 (Registry Identifier)

7625A-008

CXA-NP-11-04 (Other Identifier)

Details and patient eligibility

About

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%.

Enrollment: 726 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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726 participants in 2 patient groups

Ceftolozane/tazobactam

Experimental group

Description:

Participants receive 3000 mg ceftolozane/tazobactam intravenous IV (comprising 2000 mg ceftolozane and 1000 mg tazobactam) every 8 hours for 8-14 days.

Treatment:

Drug: Ceftolozane/tazobactam

Meropenem

Active Comparator group

Description:

Participants receive 1000 mg meropenem IV every 8 hours for 8-14 days.

Treatment:

Drug: Meropenem