A clinical trial to study the safety, efficacy and tolerability of the drug Ceftazidime-Avibactam(CAZ-AVI) versus Meropenem in patients with Nosocomial Pneumonia(NP) including Ventilator Associated Pneumonia(VAP).

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2014/05/004622
• Date of registration: 26-05-2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A clinical trial to study the safety, efficacy and tolerability of the drug Ceftazidime-Avibactam(CAZ-AVI) versus Meropenem in patients with Nosocomial Pneumonia(NP) including Ventilator Associated Pneumonia(VAP).
• Scientific title: 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 - REPROVE
• Date of first enrolment: 19-06-2014
• Target sample size: 1600
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7461
• Study type: Interventional
• Study design: Randomized, Parallel Group, Multiple Arm Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Double Blind Double Dummy
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Bulgaria, Chile, China, Czech Republic, France, Hungary, India, Italy, Japan, Mexico, Peru, Poland, Republic of Korea, Russian Federation, South Africa, Spain, Turkey, Ukraine, United Kingdom, Viet Nam

Contacts

• Name: Dr Bhavesh Kotak
• Affiliation: AstraZeneca Pharma India Ltd.

• Name: Ms Ranju Sharma
• Affiliation: AstraZeneca Pharma India Ltd.

Key inclusion & exclusion 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 last dose of IV study therapy.



• Onset of symptoms more than or equal to 48 hours after admission or less than 7 days after discharge from an inpatient acute or chronic care facility.



• New or worsening infiltrate on chest X-ray obtained within 48 hours prior to randomization.



• At least 1 of the following systemic signs: Fever (temperature more than 38 degree C) or hypothermia (rectal/core temperature less than 35 degree C); White blood cell count more than10,000 cells/mm3, or White blood cell count less than 4500 cells/mm3, or more than15% band forms.
Exclusion criteria: • 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).



• 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.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Nosocomial Pneumonia (NP) Ventilator Associated Pneumonia (VAP) Health Condition 2: J189- Pneumonia, unspecified organism

Intervention(s)

Intervention1: Ceftazidime-Avibactam: Ceftazidime plus avibactam for 7-14 days treatment;
Intravenous infusion
Control Intervention1: Meropenem: Meropenem for 7-14 days treatment;
Intravenous infusion

Primary Outcome(s)

The proportion of patients with clinical cure in the clinically modified intent-to-treat and clinically evaluable analysis sets (co-primary analyses)Timepoint: Up to 25 days from randomization



21st - 25th day from randomization

Secondary Outcome(s)

The proportion of favorable per-pathogen microbiologic responses by minimum inhibitory concentration categories in microbiologically modified intent-to-treat, microbiologically evaluable and extended-microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization and 21 to 25 from randomization

The proportion of favorable per-pathogen microbiologic responses in microbiologically modified intent-to-treat, microbiologically evaluable and extended microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization and 21 to 25 from randomization

The proportion of patients with clinical cure in patients with pathogens resistant to ceftazidime in clinically evaluable, clinically modified intent-to-treat, microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization and 21 to 25 from randomization

The proportion of patients with a favorable per-patient microbiologic response in microbiologically modified intent-to-treat, microbiologically evaluable, extended microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization and 21 to 25 from randomization

The proportion of patients discharged from hospital in the clinically evaluable, clinically modified intent-to-treat and microbiologically modified intent-to-treat analysis setsTimepoint: up to 25 days from randomization



21st - 25th day from randomization

The proportion of patients with death due to any cause (all-cause mortality) in the clinically evaluable, clinically modified intent-to-treat and microbiologically modified intent-to-treat analysis setsTimepoint: at Day 21 to 25 from randomization and Day 28 from randomization

The proportion of patients with clinical cure in clinically modified intent-to-treat, clinically evaluable, microbiologically modified intent-to-treat, microbiologically evaluable, extended microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization

The proportion of patients with clinical cure in the microbiologically modified intent-to-treat, microbiologically evaluable and extended Microbiologically evaluable analysis setsTimepoint: Up to 25 days from randomization



21st - 25th day from randomization

Safety and tolerability by incidence and severity of adverse events and serious adverse events, mortality, reasons for discontinuations of study therapy, vital signs, physical exams, electrocardiogram parameters, and clinical laboratory testsTimepoint: up to 28 days from randomization

Proportion of patients with a favorable per-patient microbiologic response in patients with pathogens resistant to ceftazidime in microbiologically modified intent-to-treat, microbiologically evaluable, extended microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization and 21 to 25 from randomization

The proportion of favorable per-pathogen microbiologic responses in patients with pathogens resistant to ceftazidime in microbiologically modified intent-to-treat, microbiologically evaluable and extended microbiologically evaluable analysis setsTimepoint: up to 14 days from randomization and 21 to 25 from randomization

Secondary ID(s)

D4281C00001

Source(s) of Monetary Support

AstraZeneca AB, 151 85 Södertälje, Sweden.

Secondary Sponsor(s)

AstraZeneca Pharma India Ltd

Ethics review

Status: Approved
Approval date: 10/07/2013
Contact:

Ethics Committee Apollo Hospital

Status: Approved
Approval date: 27/08/2013
Contact:

Ethics Committee of Bangalore Medical

Status: Approved
Approval date: 27/08/2013
Contact:

Medanta Independent Ethics Committee

Status: Approved
Approval date: 02/09/2013
Contact:

Office of the Ethics Committee

Status: Approved
Approval date: 26/09/2013
Contact:

Institution Ethics Committee

Status: Approved
Approval date: 23/10/2013
Contact:

Ethical Review Board

Status: Approved
Approval date: 24/12/2013
Contact:

Institutional Ethics Committee

Status: Approved
Approval date: 20/06/2014
Contact:

Institution Ethics Committee JSS Medical College

Status: Approved
Approval date: 15/10/2014
Contact:

Max Healthcare Ethics Committee