Healthcare-Associated PneumoniaPhase 3ASPECT-NPNCT02070757

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

A Phase 3 study testing Ceftolozane/tazobactam and Meropenem in people with Healthcare-Associated Pneumonia and Ventilator-Associated Pneumonia, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Healthcare-Associated Pneumonia, Ventilator-Associated Pneumonia, Lung Diseases
What is being tested?: Ceftolozane/tazobactam and Meropenem
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 726 participants
Where: No sites listed yet
Study dates: 2 Sep 2014to 6 Jun 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 10Show fewer

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.

About this study

Official title: A Prospective, Randomized, Double-Blind, Multicenter, Phase 3 Study to Assess the Safety and Efficacy of Intravenous Ceftolozane/Tazobactam Compared With Meropenem in Adult Patients With Ventilated Nosocomial Pneumonia

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%.

Conditions: Healthcare-Associated Pneumonia, Ventilator-Associated Pneumonia, Lung Diseases
Being tested: Ceftolozane/tazobactam, Meropenem
Medical subject headings: Healthcare-Associated Pneumonia, Pneumonia, Ventilator-Associated, Lung Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT02070757
Study group	Role	What they receive
Ceftolozane/tazobactam	Experimental	Participants receive 3000 mg ceftolozane/tazobactam intravenous IV (comprising 2000 mg ceftolozane and 1000 mg tazobactam) every 8 hours for 8-14 days. Receives: Drug: Ceftolozane/tazobactam
Meropenem	Active comparator	Participants receive 1000 mg meropenem IV every 8 hours for 8-14 days. Receives: Drug: Meropenem

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Day 28

Secondary outcomes (12)

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.
Measured: 7 to 14 days after last dose of study drug (Up to ~Day 30)
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.
Measured: Day 28
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.
Measured: 7 to 14 days after last dose of study drug (Up to ~Day 30)
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.
Measured: 7 to 14 days after last dose of study drug (Up to ~Day 30)
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.
Measured: 7 to 14 days after last dose of study drug (Up to ~Day 30)
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.
Measured: Day 14
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.
Measured: Within 24 hours after last dose of study drug (Up to ~Day 15)
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.
Measured: Within 24 hours after last dose of study drug (Up to ~Day 15)
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."
Measured: 28 to 35 days after the last dose of study drug (Up to ~Day 50)
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.
Measured: Up to 35 days after last dose of study drug (Up to ~Day 50)
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.
Measured: Up to 35 days after last dose of study drug (Up to ~Day 50)
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.
Measured: Up to 14 days after the first dose of study drug (Up to ~Day 15)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Sep 20146 Jun 2018

First posted25 Feb 2014 (estimated)
Study start2 Sep 2014
Primary completion15 May 2018
Study completion6 Jun 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for Healthcare-Associated PneumoniaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 726 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02070757
Sponsor's protocol ID: 7625A-008
Other IDs: CXA-NP-11-04, 163338, MK-7625A-008
Acronym: ASPECT-NP
Status last verified: Apr 2020
First submitted: 19 Feb 2014
Last updated: 5 May 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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 2015 Aug 25.
PubMed 26096377
Martin-Loeches I, Shorr AF, Wunderink RG, Kollef MH, Timsit JF, Yu B, Huntington JA, Jensen E, Bruno CJ. Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial. Ann Intensive Care. 2023 Feb 11;13(1):8. doi: 10.1186/s13613-022-01084-8.
PubMed 36773112
Kollef MH, Timsit JF, Martin-Loeches I, Wunderink RG, Huntington JA, Jensen EH, Yu B, Bruno CJ. Outcomes in participants with failure of initial antibacterial therapy for hospital-acquired/ventilator-associated bacterial pneumonia prior to enrollment in the randomized, controlled phase 3 ASPECT-NP trial of ceftolozane/tazobactam versus meropenem. Crit Care. 2022 Dec 1;26(1):373. doi: 10.1186/s13054-022-04192-w.
PubMed 36457059
Paterson DL, Bassetti M, Motyl M, Johnson MG, Castanheira M, Jensen EH, Huntington JA, Yu B, Wolf DJ, Bruno CJ. Ceftolozane/tazobactam for hospital-acquired/ventilator-associated bacterial pneumonia due to ESBL-producing Enterobacterales: a subgroup analysis of the ASPECT-NP clinical trial. J Antimicrob Chemother. 2022 Aug 25;77(9):2522-2531. doi: 10.1093/jac/dkac184.
PubMed 35781341
Shorr AF, Bruno CJ, Zhang Z, Jensen E, Gao W, Feng HP, Huntington JA, Yu B, Rhee EG, De Anda C, Basu S, Kollef MH. Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial. Crit Care. 2021 Oct 2;25(1):354. doi: 10.1186/s13054-021-03773-5.
PubMed 34600585
Timsit JF, Huntington JA, Wunderink RG, Shime N, Kollef MH, Kivistik U, Novacek M, Rea-Neto A, Martin-Loeches I, Yu B, Jensen EH, Butterton JR, Wolf DJ, Rhee EG, Bruno CJ. Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial. Crit Care. 2021 Aug 11;25(1):290. doi: 10.1186/s13054-021-03694-3.
PubMed 34380538
Castanheira M, Johnson MG, Yu B, Huntington JA, Carmelitano P, Bruno C, Rhee EG, Motyl M. Molecular Characterization of Baseline Enterobacterales and Pseudomonas aeruginosa Isolates from a Phase 3 Nosocomial Pneumonia (ASPECT-NP) Clinical Trial. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02461-20. doi: 10.1128/AAC.02461-20. Print 2021 Feb 17.
PubMed 33318005
Lodise T, Yang J, Puzniak LA, Dillon R, Kollef M. Healthcare Resource Utilization of Ceftolozane/Tazobactam Versus Meropenem for Ventilated Nosocomial Pneumonia from the Randomized, Controlled, Double-Blind ASPECT-NP Trial. Infect Dis Ther. 2020 Dec;9(4):953-966. doi: 10.1007/s40121-020-00343-0. Epub 2020 Sep 30.
PubMed 32996064
Huntington JA, Yu B, Li L, Jensen E, Bruno C, Boakye M, Zhang Z, Gao W, Feng HP, Rhee E. Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP). Antimicrob Agents Chemother. 2020 Nov 17;64(12):e00731-20. doi: 10.1128/AAC.00731-20. Print 2020 Nov 17.
PubMed 32988827
Kollef MH, Novacek M, Kivistik U, Rea-Neto A, Shime N, Martin-Loeches I, Timsit JF, Wunderink RG, Bruno CJ, Huntington JA, Lin G, Yu B, Butterton JR, Rhee EG. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2019 Dec;19(12):1299-1311. doi: 10.1016/S1473-3099(19)30403-7. Epub 2019 Sep 25.
PubMed 31563344

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Early Identification of Pathogens in Children With Respiratory Tract Infection by Mechanical Ventilation Using mNGS
VAP - Ventilator Associated Pneumonia
RecruitingPhase 4
EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics
Blood Stream Infections, Ventilator Associated Pneumonia
Not yet recruiting
Mobile-Based Microlearning for Improving ICU Nurses' Adherence to Ventilator-Associated Pneumonia Prevention Protocols
Ventilator-Associated Pneumonia
Recruiting
Immediate Versus Substantiated Antibiotic Therapy in Suspected Non-Severe Ventilator-Associated Pneumonia
Ventilator-Associated Pneumonia (VAP)

All Healthcare-Associated Pneumonia trials

Study at a glance

From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective, Randomized, Double-Blind, Multicenter, Phase 3 Study to Assess the Safety and Efficacy of Intravenous Ceftolozane/Tazobactam Compared With Meropenem in Adult Patients With Ventilated Nosocomial Pneumonia
ClinicalTrials.gov ID: NCT02070757
Acronym / sponsor ID: ASPECT-NP / 7625A-008
Conditions: Healthcare-Associated Pneumonia, Ventilator-Associated Pneumonia, Lung Diseases
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 726 participants (actual)
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: 2 Sep 2014 (actual)
Primary completion: 15 May 2018 (actual)
Study completion: 6 Jun 2018 (actual)
First posted: 25 Feb 2014 (estimated)
Results: Posted 31 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Ceftolozane/tazobactam	Experimental	Drug: Ceftolozane/tazobactamParticipants receive 3000 mg ceftolozane/tazobactam intravenous IV (comprising 2000 mg ceftolozane and 1000 mg tazobactam) every 8 hours for 8-14 days.
Meropenem	Active comparator	Drug: MeropenemParticipants receive 1000 mg meropenem IV every 8 hours for 8-14 days.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (10 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

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

Primary outcome

Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28
Time frame: 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.

12 secondary outcomes

Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population
Time frame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
Percentage of Participants With All Cause Mortality in the Microbiological Intent-to-Treat (mITT) Population - Day 28
Time frame: Day 28
Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population
Time frame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
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
Time frame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
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)
Time frame: 7 to 14 days after last dose of study drug (Up to ~Day 30)
Percentage of Participants With All-Cause Mortality in the Intent-to-Treat (ITT) Population - Day 14
Time frame: Day 14
Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population
Time frame: Within 24 hours after last dose of study drug (Up to ~Day 15)
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
Time frame: Within 24 hours after last dose of study drug (Up to ~Day 15)
Percentage of Participants With Clinical Response of Clinical Cure at the Late Follow-up (LFU) Visit in the Clinically Evaluable (CE) Population
Time frame: 28 to 35 days after the last dose of study drug (Up to ~Day 50)
Percentage of Participants Who Report 1 or More Adverse Event (AE)
Time frame: Up to 35 days after last dose of study drug (Up to ~Day 50)
Percentage of Participants With Any Serious Adverse Event (SAE)
Time frame: Up to 35 days after last dose of study drug (Up to ~Day 50)
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE)
Time frame: Up to 14 days after the first dose of study drug (Up to ~Day 15)

Results and safety

Results posted to the registry on 31 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ceftolozane/Tazobactam	362	245
Meropenem	364	250

Primary outcome: Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28

Time frame: Day 28. Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Ceftolozane/Tazobactam n = 362	Meropenem n = 364
Value	24.0 (18.83 to 27.39)	25.3 (19.96 to 28.41)

Ceftolozane/Tazobactam vs Meropenem: Difference in Percentage of Participants: 1.1 (95% CI -5.13 to 7.39)

Population analysed: The ITT population consisted of all randomized participants with documented informed consent, regardless of whether or not they received study drug.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study drug up to 35 days after last dose of study drug (Up to ~Day 50). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ceftolozane/Tazobactam	152 of 361 (42.1%)	113 of 361 (31.3%)	105 of 361
Meropenem	129 of 359 (35.9%)	111 of 359 (30.9%)	101 of 359

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26096377Xiao 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 2015 Aug 25.
Derived from this study: PubMed 36773112Martin-Loeches I, Shorr AF, Wunderink RG, Kollef MH, Timsit JF, Yu B, Huntington JA, Jensen E, Bruno CJ. Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial. Ann Intensive Care. 2023 Feb 11;13(1):8. doi: 10.1186/s13613-022-01084-8.
Derived from this study: PubMed 36457059Kollef MH, Timsit JF, Martin-Loeches I, Wunderink RG, Huntington JA, Jensen EH, Yu B, Bruno CJ. Outcomes in participants with failure of initial antibacterial therapy for hospital-acquired/ventilator-associated bacterial pneumonia prior to enrollment in the randomized, controlled phase 3 ASPECT-NP trial of ceftolozane/tazobactam versus meropenem. Crit Care. 2022 Dec 1;26(1):373. doi: 10.1186/s13054-022-04192-w.
Derived from this study: PubMed 35781341Paterson DL, Bassetti M, Motyl M, Johnson MG, Castanheira M, Jensen EH, Huntington JA, Yu B, Wolf DJ, Bruno CJ. Ceftolozane/tazobactam for hospital-acquired/ventilator-associated bacterial pneumonia due to ESBL-producing Enterobacterales: a subgroup analysis of the ASPECT-NP clinical trial. J Antimicrob Chemother. 2022 Aug 25;77(9):2522-2531. doi: 10.1093/jac/dkac184.
Derived from this study: PubMed 34600585Shorr AF, Bruno CJ, Zhang Z, Jensen E, Gao W, Feng HP, Huntington JA, Yu B, Rhee EG, De Anda C, Basu S, Kollef MH. Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial. Crit Care. 2021 Oct 2;25(1):354. doi: 10.1186/s13054-021-03773-5.
Derived from this study: PubMed 34380538Timsit JF, Huntington JA, Wunderink RG, Shime N, Kollef MH, Kivistik U, Novacek M, Rea-Neto A, Martin-Loeches I, Yu B, Jensen EH, Butterton JR, Wolf DJ, Rhee EG, Bruno CJ. Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial. Crit Care. 2021 Aug 11;25(1):290. doi: 10.1186/s13054-021-03694-3.
Derived from this study: PubMed 33318005Castanheira M, Johnson MG, Yu B, Huntington JA, Carmelitano P, Bruno C, Rhee EG, Motyl M. Molecular Characterization of Baseline Enterobacterales and Pseudomonas aeruginosa Isolates from a Phase 3 Nosocomial Pneumonia (ASPECT-NP) Clinical Trial. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e02461-20. doi: 10.1128/AAC.02461-20. Print 2021 Feb 17.
Derived from this study: PubMed 32996064Lodise T, Yang J, Puzniak LA, Dillon R, Kollef M. Healthcare Resource Utilization of Ceftolozane/Tazobactam Versus Meropenem for Ventilated Nosocomial Pneumonia from the Randomized, Controlled, Double-Blind ASPECT-NP Trial. Infect Dis Ther. 2020 Dec;9(4):953-966. doi: 10.1007/s40121-020-00343-0. Epub 2020 Sep 30.
Derived from this study: PubMed 32988827Huntington JA, Yu B, Li L, Jensen E, Bruno C, Boakye M, Zhang Z, Gao W, Feng HP, Rhee E. Outcomes in Participants with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane/Tazobactam Treatment of Nosocomial Pneumonia (ASPECT-NP). Antimicrob Agents Chemother. 2020 Nov 17;64(12):e00731-20. doi: 10.1128/AAC.00731-20. Print 2020 Nov 17.
Derived from this study: PubMed 31563344Kollef MH, Novacek M, Kivistik U, Rea-Neto A, Shime N, Martin-Loeches I, Timsit JF, Wunderink RG, Bruno CJ, Huntington JA, Lin G, Yu B, Butterton JR, Rhee EG. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2019 Dec;19(12):1299-1311. doi: 10.1016/S1473-3099(19)30403-7. Epub 2019 Sep 25.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 May 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With All Cause Mortality in the Intent-to-Treat (ITT) Population - Day 28 (time frame: Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02070757, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2020.