PHASE III, RANDOMIZED, MULTICENTRE, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP COMPARATIVE STUDY TO DETERMINE THE EFFICACY, SAFETY AND TOLERABILITY OF CEFTAZIDIME-AVIBACTAM (CAZ-AVI) VERSUS MEROPENEM IN THE TREATMENT OF NOSOCOMIAL PNEUMONIA (NP) INCLUDING VENTILATOR ASSOCIATED PNEUMONIA (VAP) IN HOSPITALISED ADULTS

Not Applicable

• Conditions: -J159 Bacterial pneumonia, unspecified; Bacterial pneumonia, unspecified; J159

• Registration Number: PER-003-13
• Lead Sponsor: ASTRAZENECA PERU S.A.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-04-08
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: Not specified
• Target Recruitment: 2

Inclusion Criteria

1.Patient must provide a signed written informed consent prior to any study-specific procedures.
2.Adults ≥18 years and ≤ 90 years of age
3.Female patient is authorized to participate in this clinical study if at least one of the following criteria are met:
(a)Surgical sterilization, including, hysterectomy and/or bilateral oopherectomy and/or bilateral salpingectomy, but excluding bilateral tubal occlusion;
(b)Age >=50 and post menopausal as defined by amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments
(c)Age <50 and post menopausal as defined by LH and FSH levels in the post menopausal range PLUS amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments (If LH and FSH cannot be documented then the patient must meet criterion d)
(d)Both of the following conditions are met:
Patient has a negative serum pregnancy test (serum β-human chorionic gonadotropin [β-hCG]) within 1 day prior to randomization (if the results of the serum β-hCG cannot be obtained prior to dosing of IP, a patient may be enrolled on the basis of a negative urine pregnancy test, though serum β-hCG must still be obtained). If either test is positive, the patient must be excluded. Since urine and serum tests may miss a pregnancy in the first days after conception, relevant menstrual history and sexual history, including methods of contraception, should be considered.
Patient agrees not to attempt pregnancy while receiving study drugs and for a period of 7 days after last dose of IV study therapy and agrees to the use of the following acceptable methods of contraception: Prior to and during the study, use of an intrauterine device (with copper banded coil), levonorgestrel intrauterine system (eg, Mirena®), regular medroxyprogesterone injections (Depo-Provera®), or sexual intercourse with only vasectomised partners, or complete sexual abstinence for the recommended period. Note: Oral contraceptives should not be used as the sole method of birth control because the effect of CAZ-AVI on the efficacy of oral contraceptives has not yet been established. Barrier methods (such as male condom or diaphragm with spermicide) can be used if another method of acceptable contraception (not oral contraceptives) is also used.
4.Onset of symptoms ≥48 hours after admission or <7 days after discharge from an inpatient acute or chronic care facility.
5.New or worsening infiltrate on chest X-ray obtained within 48 hours prior to randomization .
6.At least 1 of the following systemic signs:
Fever (temperature >38°C) or hypothermia (rectal/core temperature <35°C)
White blood cell (WBC) count >10,000 cells/mm3, or WBC count <4500 cells/mm3, or >15% band forms
7.At least 2 of the following respiratory signs or symptoms:
A new onset of cough (or worsening of cough)
Production of purulent sputum or endotracheal secretions
Auscultatory findings consistent with pneumonia/pulmonary consolidation (eg, rales, rhonchi, bronchial breath sounds, dullness to percussion, egophony)
Dyspnea, tachypnea or hypoxemia (O2 saturation <90% or pO2 <60 mmHg while breathing room air)
A need for mechanical ventilation or, for already ventilated patients, acute changes made in the ventilator support system to enhance oxygenation, as deter

Exclusion Criteria

1.When culture results from a 48 hour period prior to randomization are available [Note: This can be from any culture and not just the baseline culture], any of the following is present:
The patient is found to have NP caused by S. aureus and/or Streptococcus pneumoniae without concomitant infection with a Gram-negative pathogen. (Polymicrobial infections with Gram-positive pathogens are permitted as long as a Gram-negative pathogen is also present)
The patient is found to have NP caused by a Gram-negative species not expected to respond to CAZ-AVI and/or meropenem (e.g., Acinetobacter baumanii, Stenotrophomonas spp). Note: the patient is allowed to participate in the study if the investigator considers that the species is a colonizer which does not warrant specific treatment
The patient is found to have NP caused by a Gram-negative pathogen demonstrating resistance to carbapenems.
2.When a Gram stain result from a BAL specimen, mini BAL, or PSB specimen is available, the Gram stain shows Gram-positive organisms without the presence of Gram-negative organisms. (A Gram stain demonstrating no organisms does not preclude enrolment.)
3.The total duration of antibiotic exposure for antibiotics whose administration begins in the 48 hours prior to randomization is longer than 24 hours, unless the pathogen(s) identified was resistant to the antimicrobial agent received (based on local laboratory results) and the patient has shown objective signs of worsening despite therapy as demonstrated by: Increased oxygen requirement and/or two of the following: increased dyspnea, increased purulent sputum, increased tachypnea, increased white blood cell (WBC) count.
(As an example, the administration of more than 3 doses of a q8h antibiotic or more than 1 dose of a q24h antibiotic in the 48 hours prior to randomization would render the patient ineligible for enrolment. In situations where two or more antibiotics were administered such that their exposures overlap, total simultaneous exposure” hours are counted and must not be > 24 hours - See sample figure below, where the bars represent the durations of antibiotic exposure of antibiotics A and B. Also, note that the whole exposure of B is counted, not just up to the point of randomization):
4.Patient with history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to carbapenem or cephalosporin or other beta-lactam antibiotics.
5.Patient with a history of serious allergy, hypersensitivity or any serious reaction to BOTH vancomycin and linezolid unless the culture result is known prior to enrolment and no Gram-positive organism requiring treatment is present.
6.Pulmonary disease that precludes evaluation of therapeutic response (including, but not limited to, lung cancer, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection or recent pulmonary embolism).
7.Patients with lung abscess, pleural empyema or post obstructive pneumonia.
8.Patient with concurrent infection that may interfere with the evaluation of response to the study antibiotic.
9.Patients with a need for effective concomitant systemic antibacterials in addition to those designated per protocol.
10.Patient is a recipient of a lung or heart transplant.
11.Patient is immunocompromised and at risk of infection by opportunistic pathogens including, but not limited to the following:

Study & Design

• Study Type: Interventional
• Study Design: Not specified