Clinical trial NCT04882085: Efficacy and Safety of CAZ-AVI in the Treatment of Infections Due to Carbapenem-resistant G- Pathogens in Chinese Adults
Official title: AN OPEN-LABEL, RANDOMIZED, MULTI-CENTER, ACTIVE-CONTROLLED STUDY TO ESTIMATE THE EFFICACY AND SAFETY OF CEFTAZIDIME-AVIBACTAM (CAZ-AVI) VERSUS BEST AVAILABLE TREATMENT (BAT) IN THE TREATMENT OF INFECTIONS DUE TO CARBAPENEM-RESISTANT GRAM-NEGATIVE PATHOGENS IN CHINESE ADULTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Urinary Tract Infection
Acute Pyelonephritis
Hospital Acquired Pneumonia
Ventilator-associated Pneumonia
Bacteremia
Intra-abdominal Infection
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, randomized, multi-center, interventional, active-controlled Phase 4 study to evaluate the efficacy and safety of CAZ-AVI versus BAT in the treatment of infected participants with selected infection types (Hospital Acquired Pneumonia \[HAP\] (including Ventilator-Associated Pneumonia \[VAP\]); Complicated Urinary-Tract Infection \[cUTI\]; Complicated Intra-Abdominal Infection \[cIAI\]; Bloodstream Infection \[BSI\]) due to carbapenem-resistant Gram-negative pathogens in China.This study will be an estimation study. The statistical inference will be based on point estimate and confidence interval.


Eligibility criteria: Inclusion Criteria:

* Male or female \>18 years of age
* Participant must have a diagnosis of an infection (HAP/VAP, cUTI, cIAI, BSI) due to confirmed carbapenem-resistant aerobic Gram-negative pathogens, requiring administration of IV antibacterial therapy
* Participant who had received appropriate prior empiric antibacterial therapy for a carbapenem-resistant pathogen must meet at least 1 of the following criteria: no or no more than 24h; worsening of objective symptoms or signs after at least 48 hours of antibacterial therapy; no change of objective symptoms or signs after at least 72 hours of antibacterial therapy.
* Capable of giving signed informed consent

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 more than 21 days of treatment
* Participants who need more than 3 systemic antibiotics as part of best available treatment (BAT)
* 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).
* Participant is pregnant or breastfeeding.
* Acute Physiology and Chronic Health Evaluation (APACHE) II score \>30 or \<10 using the most recent available data.

Primary outcomes:
measure: Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit - Microbiologically Modified Intent-to-Treat (mMITT) Analysis Set
timeFrame: At TOC visit (From Day 21 up to Day 24)
Secondary outcomes:
measure: Percentage of Participants With Clinical Cure at TOC Visit - Microbiologically Evaluable (ME) Analysis Set
timeFrame: At TOC visit (From Day 21 up to Day 24)
measure: Percentage of Participants With Clinical Cure at End of Treatment (EOT) Visit -mMITT Analysis Set
timeFrame: At EOT visit (up to 24 hours after the last infusion on Day 14)
measure: Percentage of Participants With Clinical Cure at EOT Visit - ME Analysis Set
timeFrame: At EOT visit (up to 24 hours after the last infusion on Day 14)
measure: Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit - mMITT Analysis Set
timeFrame: At TOC visit (From Day 21 up to Day 24)
measure: Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit - ME Analysis Set
timeFrame: At TOC visit (From Day 21 up to Day 24)
measure: Percentage of Participants With Favorable Per-Participant Microbiological Response at EOT Visit - mMITT Analysis Set
timeFrame: At EOT visit (Up to 24 hours after last infusion on Day 14)
measure: Percentage of Participants With Favorable Per-Participant Microbiological Response at EOT Visit - ME Analysis Set
timeFrame: At EOT visit (Up to 24 hours after last infusion on Day 14)
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response at TOC Visit - mMITT Analysis Set
timeFrame: At TOC visit (From Day 21 up to Day 24)
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT Visit - mMITT Analysis Set
timeFrame: At EOT visit (Up to 24 hours after last infusion on Day 14)
measure: Percentage of Participants Who Died Due to Any Cause Until Day 28
timeFrame: From first dose of study intervention (Day 1) up to Day 28
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From start of study treatment on Day 1 up to 32 days after the last dose of study intervention (Up to 46 days)
measure: Number of Participants With Discontinuation Due to Adverse Events
timeFrame: From start of study treatment on Day 1 up to 32 days after the last dose of study intervention (Up to 46 days)
measure: Number of Participants With Potentially Clinically Significant Post-baseline Hematology Values
timeFrame: From first dose of study treatment (Day 1) until TOC (Up to Day 24)
measure: Number of Participants With Potentially Clinically Significant Post-baseline Clinical Chemistry Values
timeFrame: From first dose of study treatment (Day 1) until TOC (Up to Day 24)
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical
state: Anhui
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Chizhou
country: China
facility: Chizhou People's Hospital
state: Anhui
city: Fuyang
country: China
facility: Fuyang People's Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The Second People's Hospital of Shenzhen
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical College
state: Guangxi
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: NanYang central hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan provincial people's hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan provincial people's hospital
state: Henan
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia Autonomous Region
city: Jiangyin
country: China
facility: Jiangyin People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu province
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
city: Chengdu
country: China
facility: Chengdu Xinhua Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Chest Hospital
state: Tianjin
city: Kunming
country: China
facility: The First People's Hospital of Kunming (South Hospital)
state: Yunnan
city: Kunming
country: China
facility: The First people's Hospital of Kunming
state: Yunnan
city: Kunming
country: China
facility: The First People's Hospital of Kunming Ganmei Hospital (North Hospital)
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Lishui
country: China
facility: Lishui People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: The 2nd Affiliated Hospital of WMU
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou Central Hospital
state: Zhejiang
city: Jiangyin
country: China
facility: Jiangyin People's Hospital
city: Shanghai
country: China
facility: Shanghai Fifth People's Hospital, Fudan University
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: