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Phase 3 N=817 Randomized Quadruple-blind Treatment

A Study Comparing Ceftazidime-Avibactam Versus Meropenem in Hospitalized Adults With Nosocomial Pneumonia

Nosocomial Pneumonia (NP) · Ventilator-associated Pneumonia (VAP)

Enrolled (actual)
817
Serious AEs
16.0%
Results posted
Feb 2017
Primary outcome: Primary: The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set (Co-primary Analyses) — 245; 270; 79; 70 participants — p=0.007

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
ceftazidim-avibactam (CAZ-AVI, experimental product) (Drug); meropenem (active comparator) (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Pfizer
Primary completion
Jan 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set (Co-primary Analyses)
245; 270; 79; 70; 32; 30 0.007 sig
PRIMARY
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Evaluable at TOC Analysis Set (Co-primary Analyses)
199; 211; 58; 59 <0.001 sig
SECONDARY
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Modified Intent-to-treat Analysis Set
120; 138; 37; 34; 14; 12
SECONDARY
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Extended Microbiologically Evaluable Analysis Set
96; 103; 29; 28
SECONDARY
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Evaluable Analysis Set
85; 94; 22; 24
SECONDARY
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set
143; 161; 23; 18; 5; 5
SECONDARY
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set
292; 309; 50; 45; 14; 16
SECONDARY
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Evaluable Analysis Set
253; 268; 38; 38
SECONDARY
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable Analysis Set
125; 135; 18; 16
SECONDARY
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Evaluable Analysis Set
110; 126; 12; 12
SECONDARY
The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set
128; 148; 38; 31; 5; 5
SECONDARY
The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set
95; 118; 64; 54; 12; 12
SECONDARY
The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
112; 123; 31; 28
SECONDARY
The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
80; 89; 45; 42
SECONDARY
The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
96; 112; 26; 26
SECONDARY
The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
70; 83; 37; 35
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit
6; 5; 25; 20; 15; 18
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
4; 5; 22; 17; 13; 17
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
4; 5; 22; 17; 13; 17
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
5; 5; 21; 13; 13; 16
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
5; 3; 18; 7; 10; 16
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
5; 3; 18; 7; 10; 16
SECONDARY
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set at End of Treatment Visit
40; 45; 32; 33; 3; 2
SECONDARY
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Clinically Evaluable at End of Treatment Analysis Set
35; 42; 27; 31; 3; 2
SECONDARY
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
31; 36; 27; 31; 3; 2
SECONDARY
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Clinically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
35; 40; 28; 29; 3; 2
SECONDARY
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Clinically Evaluable at Test-of-cure Analysis Set
29; 32; 23; 22; 5; 3
SECONDARY
The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
25; 26; 23; 22; 5; 3
SECONDARY
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit
35; 39; 10; 13; 1; 2
SECONDARY
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
31; 36; 9; 13
SECONDARY
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
26; 29; 7; 11
SECONDARY
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
27; 27; 16; 23; 3; 4
SECONDARY
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
23; 21; 14; 20
SECONDARY
Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
21; 18; 9; 14
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit
3; 2; 6; 6; 5; 4
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
3; 2; 6; 5; 5; 4
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
3; 2; 6; 5; 5; 4
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
3; 2; 5; 5; 4; 4
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
4; 4; 4; 4; 11; 14
SECONDARY
The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
4; 4; 4; 4; 11; 13
SECONDARY
The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
16; 14; 6; 5; 10; 9
SECONDARY
The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in Clinically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
29; 25; 10; 6; 19; 19
SECONDARY
The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in the Clinically Evaluable at Test-of-cure Analysis Set
11; 8; 5; 4; 6; 4
SECONDARY
The Number of Patients With Death Due to Any Cause (All-cause Mortality) in Microbiologically Modified Intent-to-treat Analysis Set at Day 28
17; 16; 6; 5; 11; 11
SECONDARY
The Number of Patients With Death Due to Any Cause (All-cause Mortality) in Clinically Modified Intent-to-treat Analysis Set at Day 28
30; 27; 10; 6; 20; 21
SECONDARY
The Number of Patients With Death Due to Any Cause (All-cause Mortality) in the Clinically Evaluable at Test-of-cure Analysis Set at Day 28
12; 9; 5; 4; 7; 5
SECONDARY
The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set
170; 182; 71; 75; 71; 74
SECONDARY
The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set
355; 366; 206; 206; 201; 200
SECONDARY
The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in the Clinically Evaluable at Test-of-cure Analysis Set
256; 266; 148; 155; 144; 151

Summary

The purpose of the study is to evaluate the effects of Ceftazidime-Avibactam compared to Meropenem for treating hospitalized adults with nosocomial pneumonia including ventilator-associated pneumonia

Eligibility Criteria

Inclusion Criteria

  • 18 to 90 years of age inclusive
  • Females can participate if surgically sterile or completed menopause; if able to have children, must have negative serum pregnancy test, agree not to attempt pregnancy and use acceptable contraception while receiving study therapy and for 1 week after
  • Onset of symptoms ≥ 48 hours after admission or 38 C) or hypothermia (rectal/core temperature 10,000 cells/mm3, or White blood cell count 15% band forms.

Exclusion Criteria

  • Pulmonary disease that, in the investigator's judgment, would preclude evaluation of therapeutic response (e.g. lung cancer, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection or recent pulmonary embolism).
  • Patients with lung abscess, pleural empyema or post obstructive pneumonia.
  • Patients with an estimated creatinine clearance <16ml/min by Cockcroft Gault formula or patients expected to require haemodialysis or other renal support while on study therapy.
  • Acute hepatitis in the prior 6 months, cirrhosis, acute hepatic failure or acute decompensation of chronic hepatic failure.
  • Patients receiving hemodialysis or peritoneal dialysis.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01808092). 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.

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