Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02070757
Other study ID # 7625A-008
Secondary ID CXA-NP-11-041633
Status Completed
Phase Phase 3
First received
Last updated
Start date September 2, 2014
Est. completion date June 6, 2018

Study information

Verified date April 2020
Source Cubist Pharmaceuticals LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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%.


Recruitment information / eligibility

Status Completed
Enrollment 726
Est. completion date June 6, 2018
Est. primary completion date May 15, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

Drug:
Ceftolozane/tazobactam
Ceftolozane/tazobactam is an antibacterial consisting of a co-formulation of ceftolozane, a novel antipseudomonal cephalosporin and tazobactam, a well-established beta (ß)-lactamase inhibitor (BLI) being developed for the treatment of serious bacterial infections.
Meropenem
Meropenem is a broad spectrum injectable antibiotic widely used to treat serious infections such as ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Cubist Pharmaceuticals LLC

References & Publications (1)

Xiao AJ, Miller BW, Huntington JA, Nicolau DP. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2016 Jan;56(1):56-66. doi: 10.1002/jcph.566. Epub — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28 To demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in stratified adult participants with ventilated nosocomial pneumonia (VNP) (participants with either ventilator-associated bacterial pneumonia [VABP] or ventilated hospital-acquired bacterial pneumonia [HABP]) based on the difference in all-cause mortality rates in the intent to treat (ITT) population using a non-inferiority margin of 10%. The estimated adjusted percentage was a weighted average across all strata, constructed using Mehrotra-Railkar continuity-corrected minimum risk (MRc) stratum weights. Day 28
Secondary Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population To demonstrate the non-inferiority of ceftolozane/tazobactam versus meropenem in adult participants with ventilated nosocomial pneumonia (VNP) at the TOC visit (7 to 14 days after the end-of-therapy [EOT] visit) using a non-inferiority margin of 12.5%. Clinical response at the TOC visit was defined as cure (complete resolution with no new signs of VNP), failure (progression, relapse or recurrence of VNP) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate unless the clinical outcome at the EOT visit was failure. The estimated adjusted percentage was a weighted average across all strata, constructed using Mehrotra-Railkar continuity-corrected minimum risk (MRc) stratum weights. 7 to 14 days after last dose of study drug (Up to ~Day 30)
Secondary Percentage of Participants With All Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population - Day 28 To compare the all cause mortality rates of participants in the ceftolozane/tazobactam versus meropenem arms in microbiological intent-to-treat (mITT) population. Day 28
Secondary Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population To compare the clinical response rates of ceftolozane/tazobactam versus meropenem in adult participants with VNP (participants with either ventilator-associated bacterial pneumonia [VABP] or ventilated hospital-acquired bacterial pneumonia [HABP]) at the TOC visit in the CE population. Clinical response at the TOC visit was defined as cure (complete resolution with no new signs of VNP), failure (progression, relapse or recurrence of VNP) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate unless the clinical outcome at the EOT visit was failure. The data-as-observed (DAO) approach was used where participants with missing clinical responses, including indeterminate outcomes, are excluded from the analysis population. 7 to 14 days after last dose of study drug (Up to ~Day 30)
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 To compare the per-participant microbiological response rates of ceftolozane/tazobactam versus meropenem at the TOC visit in the microbiologically evaluable (ME) population. The per-participant microbiological response will be determined based on the individual microbiological outcomes for each baseline pathogen. A microbiological response at the TOC visit was defined as cure (baseline pathogens eradicated), failure (baseline pathogen is persistent) or indeterminate (no evaluable respiratory material). A favorable microbiological response is a microbiological cure or presumed cure. The data-as-observed (DAO) approach was used where participants with missing clinical responses, including indeterminate outcomes, are excluded from the analysis population. 7 to 14 days after last dose of study drug (Up to ~Day 30)
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) To compare the percentage of participants with a microbiological outcome of eradication or presumed eradication, by pathogen. The microbiological outcome was classified as "eradication", "presumed eradication", "persistence", 'presumed persistence", "indeterminate" or "recurrence." "Eradication" was defined as a =1- log reduction in bacterial burden of the original baseline LRT pathogen AND a per pathogen count of =10^4 colony-forming unit (CFU)/mL for endotracheal aspirate (ETA) or sputum specimens, =10^3 CFU/mL for a bronchoalveolar lavage (BAL) specimen, or =10^2 CFU/mL for a protected brush specimen (PBS) from a follow-up LRT culture. Presumed eradication was defined as an absence of material to culture (e.g. inability to obtain a culture in an extubated patient) in a patient deemed a clinical cure. 7 to 14 days after last dose of study drug (Up to ~Day 30)
Secondary Percentage of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population - Day 14 To compare the all cause mortality rates of participants (ceftolozane/tazobactam versus meropenem arms). Participants whose Day 14 mortality outcomes are missing or unknown are analysed as deceased. Day 14
Secondary Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population To compare the clinical response rates at the EOT visit for ceftolozane/tazobactam versus meropenem. Clinical response at the EOT visit was defined as cure (complete resolution with no new signs of VNP), failure (progression, relapse or recurrence of VNP) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate. Within 24 hours after last dose of study drug (Up to ~Day 15)
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 To compare the microbiological response rates of ceftolozane/tazobactam versus meropenem at the EOT visit. The per-participant microbiological response will be determined based on the individual microbiological outcomes for each baseline pathogen. A microbiological response at the EOT visit was defined as cure (baseline pathogens eradicated), failure (baseline pathogen is persistent) or indeterminate (no evaluable respiratory material). A favorable microbiological response is a microbiological cure or presumed cure. The data-as-observed (DAO) approach was used where participants with missing clinical responses, including indeterminate outcomes, are excluded from the analysis population. Within 24 hours after last dose of study drug (Up to ~Day 15)
Secondary Percentage of Participants With Clinical Response of Clinical Cure at the Late Follow-up (LFU) Visit in the Clinically Evaluable (CE) Population To compare the clinical response rates at the Late Follow-up (LFU) visit for ceftolozane/tazobactam versus meropenem in the CE population. Clinical response at the LFU visit will be classified as sustained cure, relapse, or indeterminate only in participants deemed a clinical cure at the TOC visit. A favorable clinical response is "sustained clinical cure." 28 to 35 days after the last dose of study drug (Up to ~Day 50)
Secondary Percentage of Participants Who Report 1 or More Adverse Event (AE) An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Up to 35 days after last dose of study drug (Up to ~Day 50)
Secondary Percentage of Participants With Any Serious Adverse Event (SAE) A serious adverse event (SAE) is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Up to 35 days after last dose of study drug (Up to ~Day 50)
Secondary Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE) An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. Up to 14 days after the first dose of study drug (Up to ~Day 15)
See also
  Status Clinical Trial Phase
Completed NCT05563701 - Evaluation of the LVivo Image Quality Scoring (IQS)
Completed NCT04908397 - Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension Phase 1
Terminated NCT03309358 - A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis Phase 1
Completed NCT03682354 - ESPB Versus INB With PCIA in Video-assisted Thoracic Surgery N/A
Enrolling by invitation NCT03683186 - A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension Phase 3
Completed NCT03626519 - Effects of Menthol on Dyspnoea in COPD Patients N/A
Recruiting NCT06004440 - Real World Registry for Use of the Ion Endoluminal System
Completed NCT04874948 - Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment Phase 1
Completed NCT02926768 - Phase I/II Study of CK-101 in NSCLC Patients and Other Advanced Solid Tumors Phase 1
Completed NCT01443845 - Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Dose Combinations of Long-acting β2-agonist (LABA) and Inhaled Corticosteroid (ICS) Phase 4
Completed NCT00281216 - Innate and Adaptive Immunity in Individuals Experiencing Chronic Obstructive Pulmonary Disease Exacerbations N/A
Completed NCT00269256 - Stress, Environment, and Genetics in Urban Children With Asthma N/A
Terminated NCT00233207 - IC14 Antibodies to Treat Individuals With Acute Lung Injury Phase 2
Recruiting NCT00129350 - Assessment of Heart and Heart-Lung Transplant Patient Outcomes Following Pulmonary Rehabilitation Phase 1
Active, not recruiting NCT00115297 - Montelukast for Early Life Wheezing Phase 2/Phase 3
Completed NCT00091767 - Genetic Studies in Difficult to Treat Asthma: TENOR N/A
Completed NCT00094276 - Intervention for Improving Asthma Care for Minority Children in Head Start N/A
Completed NCT00233168 - Effectiveness of Public Health Model of Latent Tuberculosis Infection Control for High-Risk Adolescents N/A
Completed NCT00083798 - Family Linkage Study of Obstructive Sleep Apnea (OSA) in Iceland N/A
Completed NCT00069823 - Study of Acid Reflux in Asthma Phase 3