Efficacy and Safety of Ceftazidime-Avibactam (CAZ-AVI) in Chinese Participants With HAP (Including VAP)

Pfizer235 enrolled

Overview

This is a prospective, single arm, open-label, multi-center clinical study evaluating the effectiveness and safety of CAZ-AVI in participants with HAP (including VAP), who have initiated treatment with CAZ-AVI in an inpatient hospital setting. The duration of antibiotic treatment with the CAZ-AVI is 7-14 days. Participants must receive intravenously (IV) CAZ-AVI in the hospital for at least 7 full days. There are no formal hypothesis tests planned for this study. The number and percent of participants having clinical cure, failure, and indeterminate at TOC visit in the cMITT analysis population will be summarized.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

235

Conditions

Hospital-Acquired Pneumonia

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female participants ≥18 and ≤90 years of age. * Onset of symptoms ≥48 hours after admission or \<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 screening. * Participants have systemic signs and respiratory signs or symptoms of HAP/VAP Exclusion Criteria: * Other medical or psychiatric condition may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Participant is expected to require a treatment course for HAP longer than 14 days. * The total duration of antibiotic exposure for antibiotics whose administration begins in the 48 hours is longer than 24 hours. * Previous administration with an investigational drug within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). * Acute Physiology and Chronic Health Evaluation (APACHE) II score \>30 or \<10 using the most recent available data.

Locations (56)

Fuyang People's Hospital

Fuyang, Anhui, China

Peking University Third Hospital

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Zhongshan Hospital Xiamen University

Xiamen, Fujian, China

Guangzhou First People's Hospital

Guangzhou, Guangdong, China

Outcomes

Primary Outcomes

Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: Clinical Modified Intent-to-Treat (cMITT) Population

Clinical cure: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at end of treatment (EOT), and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive. Gram negative is abbreviated as gram -ve and gram positive as gram +ve.

Time frame: TOC visit: any day from Day 21 to 25

Secondary Outcomes

Percentage of Participants With Clinical Cure at EOT Visit: cMITT Population

Clinical cure: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/ VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days)

Percentage of Participants With Clinical Cure at EOT and TOC Visit: Microbiological Modified Intent-to-Treat (mMITT) Population

Clinical cure at EOT: participants were considered to be a success for clinical response at EOT visit if the participants were alive and all signs and symptoms of pneumonia were resolved or improved such that all antibacterial therapies for HAP/VAP were stopped. No antibacterial therapy other than those outlined by the protocol was administered for HAP prior to EOT. Clinical cure at TOC: participants were considered to be a success for clinical response at TOC visit if the participants were not a clinical failure at EOT, and the participants were alive and all signs and symptoms of pneumonia were resolved or improved to an extent that no antibacterial therapy for HAP was taken between EOT and TOC inclusive.

Time frame: EOT visit: within 24 hours after the completion of the last infusion of study intervention (study treatment was a minimum of 7 days and maximum of 14 days); TOC visit: any day from Day 21 to 25

Percentage of Participants With Favorable Per-Participant Microbiological Response at the EOT and TOC Visits: mMITT Population

For participants from whom only 1 causative pathogen is isolated, the overall microbiological response assessment was based on the microbiological response assessment for that pathogen. For participants from whom more than 1 baseline pathogen was isolated, the overall microbiological response assessment was "favorable" only if the microbiological response assessment for each of the baseline pathogens isolated was "favorable". Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-participant microbiological response are recorded.

Percentage of Participants With Favorable Per-Pathogen Microbiological Response at the EOT and TOC Visits: mMITT Population

Favorable microbiological response included eradication (an adequate source specimen demonstrated absence of the original baseline pathogen) and presumed eradication (an adequate source specimen was not available to culture and the participant was assessed as a clinical cure). In this outcome measure percentage of participants with favorable per-pathogen microbiological response are recorded.

Percentage of Participants With Clinical Cure at the EOT and TOC Visits in Participants With Gram-negative Baseline Pathogens Resistant to Ceftazidime: mMITT Population

Percentage of Participants With Favorable Per-Participant Microbiologic Response at the EOT and TOC Visits in Participants With Gram-negative Baseline Pathogens Resistant to Ceftazidime: mMITT Population

Percentage of Participants With Death Due to Any Cause at the TOC Visit and at Day 28 Visit: cMITT Population

Time frame: TOC visit: any day from Day 21 to 25; Day 28

Percentage of Participants With Death Due to Any Cause at the TOC Visit and at Day 28 Visit: mMITT Population

Time frame: TOC visit: any day from Day 21 to 25; Day 28

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all non-SAEs that occurred in the study. TEAEs were AEs between first dose of study treatment and up to 32 days post last dose that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Number of Participants With Clinically Significant Post-Baseline Laboratory Test Abnormalities

Hematology: Hemoglobin (Hg), hematocrit, erythrocytes: less than (\<)0.8\*lower limit of normal (LLN) \& change (chg) more than (\>)20% decrease (dec); platelets: \<0.65\*LLN \& chg \>50% dec \&, \>1.5\* upper limit of normal (ULN) \& chg \>100% increase (inc); leukocytes: \<0.65\*LLN \& chg \>60% dec \&, \>1.6\*ULN \& chg \>100% inc; lymphocytes, \<0.25\*LLN \& chg \>75% dec; neutrophils: \<0.65\*LLN \& chg \>75% dec \&, \>1.6\*ULN \& chg \>100% inc; basophils, monocytes: \>4.0\* ULN \& chg \>300% inc. Clinical chemistry: bilirubin: \>2.0\*ULN \& chg \>150% inc; aspartate aminotransferase (AT) \& Alanine AT: \>3.0\*ULN \& chg \>200% inc; alkaline phosphatase \<0.5\*LLN \& chg \>80% dec \& \>2.0\*ULN \& chg \>100% inc; creatinine: \>2.0\*ULN \& \>chg 100% inc; sodium: \<0.85\*LLN \& chg \>10% dec \& \>1.1\*ULN \& chg \>10% inc; potassium \& chloride: \<0.8\*LLN \& chg \>20% dec \& \>1.2\*ULN \& chg \>20% dec; calcium: \<0.7\*LLN \& chg \>30% dec \& bicarbonate: \<0.7\*LLN \& chg \>40% dec. Clinical significance was judged by investigator.

Time frame: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)

Number of Participants With Vital Signs Data According to Pre-defined Criteria

Vital signs included diastolic blood pressure (millimeters of mercury \[mmHg\]); pulse rate (beats per minute \[bpm\]) and systolic blood pressure (mmHg). Pre-defined criteria: Diastolic blood pressure: Value \<50 mmHg, Diastolic blood pressure: Change more than or equal to (\>=) 20 mmHg increase, Diastolic blood pressure: Change \>= 20 mmHg decrease, Pulse rate: Value \<40 bpm, Pulse rate: Value \>120 bpm, Systolic blood pressure: Value \<90 mmHg, Systolic blood pressure: Change \>= 30 mmHg increase, Systolic blood pressure: Change \>= 30 mmHg decrease. One participant could have more than one vital sign abnormality.

Time frame: Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days)