Efficacy and Safety of Ceftazidime-Avibactam (CAZ-AVI) in Chinese Participants With HAP (Including VAP)
- Conditions
- Hospital-Acquired Pneumonia
- Interventions
- Drug: Zavicefta, Ceftazidime-Avibactam
- Registration Number
- NCT04774094
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 235
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CAZ-AVI Zavicefta, Ceftazidime-Avibactam -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: Clinical Modified Intent-to-Treat (cMITT) Population TOC visit: any day from Day 21 to 25 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Clinical Cure at EOT Visit: cMITT Population 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) 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.
Percentage of Participants With Clinical Cure at EOT and TOC Visit: Microbiological Modified Intent-to-Treat (mMITT) Population 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 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.
Percentage of Participants With Favorable Per-Participant Microbiological Response at the EOT and TOC Visits: mMITT Population 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 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 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 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 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 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.
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 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 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 Death Due to Any Cause at the TOC Visit and at Day 28 Visit: cMITT Population 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 TOC visit: any day from Day 21 to 25; Day 28 Number of Participants With Treatment Emergent Adverse Events (TEAEs) Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) 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.
Number of Participants With Clinically Significant Post-Baseline Laboratory Test Abnormalities Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) 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.
Number of Participants With Vital Signs Data According to Pre-defined Criteria Day 1 up to 32 days after last dose of CAZ-AVI (maximum up to 46 days; maximum treatment duration was of 14 days) 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.
Trial Locations
- Locations (53)
Qingyuan People's Hospital
🇨🇳Qingyuan, Guangdong, China
Shenzhen People's Hospital
🇨🇳Shenzhen, Guangdong, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Shanghai Fifth People's Hospital, Fudan University
🇨🇳Shanghai, China
Zhejiang Hospital
🇨🇳Hangzhou, Zhejiang, China
The 2nd Affiliated Hospital of WMU
🇨🇳Wenzhou, Zhejiang, China
Fuyang People's Hospital
🇨🇳Fuyang, Anhui, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Huizhou Central People's Hospital
🇨🇳Huizhou, Guangdong, China
Affiliated Hospital of Hebei University
🇨🇳Baoding, Hebei, China
The Second People's Hospital of Shenzhen
🇨🇳Shenzhen, Guangdong, China
The Affiliated Hospital of Zunyi Medical University
🇨🇳Zunyi, Guizhou, China
Henan provincial people's hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Taizhou People's Hospital
🇨🇳Taizhou, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Affiliated Hospital of Jiangnan University
🇨🇳Wuxi, Jiangsu, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Chengdu Xinhua Hospital
🇨🇳Chengdu, Sichuan, China
Dongyang People's Hospital
🇨🇳Dongyang, Zhejiang, China
Wenzhou Central Hospital
🇨🇳Wenzhou, Zhejiang, China
Seventh Medical Center, The General Hospital of People's Liberation Army
🇨🇳Beijing, China
ZhuJiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Zhongshan Hospital Xiamen University
🇨🇳Xiamen, China
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
Affiliated Hospital of Guangdong Medical University
🇨🇳Zhanjiang, Guangdong, China
Sanya People's Hospital
🇨🇳Sanya, Hainan, China
The First Affiliated Hospital of Jinan University
🇨🇳Guangzhou, Guangdong, China
Central People's Hospital of Zhanjiang
🇨🇳Zhanjiang, Guangdong, China
Shiyan Renmin Hospital
🇨🇳Shiyan, Hubei, China
The First People's Hospital of Nanning
🇨🇳Nanning, Guangxi Zhuang Autonomous Region, China
NanYang First people's hospital
🇨🇳Nanyang, Henan, China
NanYang central hospital
🇨🇳Nanyang, Henan, China
Luoyang Central Hospital
🇨🇳Luoyang, Henan, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Hunan Provincial People's Hospital
🇨🇳Changsha, Hunan, China
Yueyang People's Hospital
🇨🇳Yueyang, Hunan, China
Baotou Central Hospital
🇨🇳Baotou, Inner Mongolia Autonomous Region, China
Huai'an First People's Hospital
🇨🇳Huai'an, Jiangsu, China
Jiangyin People's Hospital
🇨🇳Jiangyin, Jiangsu, China
The First People's Hospital of Lianyungang City
🇨🇳Lianyungang, Jiangsu, China
Jiangxi Provincial People's Hospital
🇨🇳Nanchang, Jiangxi, China
Affiliated Zhongshan Hospital of Dalian University
🇨🇳Dalian, Liaoning, China
Subei People's Hospital of Jiangsu province
🇨🇳Yangzhou, Jiangsu, China
Tianjin Chest Hospital
🇨🇳Tianjin, Tianjin, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
The First Hospital of Kunming
🇨🇳Kunming, Yunnan, China
Huashan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
General Hospital of Northern Theater Command
🇨🇳Shenyang, Liaoning, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China