Efficacy and Safety of CAZ-AVI in the Treatment of Infections Due to Carbapenem-resistant G- Pathogens in Chinese Adults

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04882085

Collaborator

(none)

Enrollment

Locations

Arms

34.1

Anticipated Duration (Months)

1.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Tract Infection Acute Pyelonephritis Hospital Acquired Pneumonia Ventilator-associated Pneumonia Bacteremia Intra-abdominal Infection	Drug: Zavicefta, Ceftazidime-Avibactam Drug: Best Available Treatment	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 26, 2021

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CAZ-AVI ceftazidime 2g plus avibactam 0.5g	Drug: Zavicefta, Ceftazidime-Avibactam CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as a 2 hour infusion every 8 hours. Dose adjustments are available for participants with CrCL ≤50 mL/min.
Active Comparator: Best Available Treatment Based on investigative site practice and local epidemiology and guideline	Drug: Best Available Treatment main treatment expected to be used as either monotherapy or in combination are colistin, tigecycline, fosfomycin, amikacin, and meropenem

Arm

Intervention/Treatment

Experimental: CAZ-AVI

ceftazidime 2g plus avibactam 0.5g

Drug: Zavicefta, Ceftazidime-Avibactam

CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as a 2 hour infusion every 8 hours. Dose adjustments are available for participants with CrCL ≤50 mL/min.

Active Comparator: Best Available Treatment

Based on investigative site practice and local epidemiology and guideline

Drug: Best Available Treatment

main treatment expected to be used as either monotherapy or in combination are colistin, tigecycline, fosfomycin, amikacin, and meropenem

Outcome Measures

Primary Outcome Measures

The percentage of participants in Microbiologically Modified Intent to Treat (mMITT) analysis set having clinical cure [Test of Cure (TOC, Day 21 - 25)]

Secondary Outcome Measures

The percentage of participants in mMITT analysis set having clinical cure [End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)]
The percentage of participants in Microbiologically Evaluable (ME) analysis set having clinical cure [End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)]
The percentage of participants in ME analysis set having clinical cure [Test of Cure (TOC, Day 21-Day 25)]
The percentage of participants in mMITT analysis set having favorable microbiological response [Test of Cure(TOC, Day 21-Day 25)]
The percentage of participants in mMITT analysis set having favorable microbiological response [End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)]
The percentage of participants in ME analysis set having favorable microbiological response [End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)]
The percentage of participants in ME analysis set having favorable microbiological response [Test of Cure(TOC, Day 21-Day 25)]
The percentage of participants who have died due to any cause [Day 28]
The number of treatment-emergent adverse events [up to 32 days after the last dose of study intervention]
The percentage of participants experiencing the AEs [up to 32 days after the last dose of study intervention]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Bengbu Medical	Bengbu	Anhui	China	233000
2	Chizhou People's Hospital	Chizhou	Anhui	China	247000
3	Fuyang People's Hospital	Fuyang	Anhui	China	236000
4	Peking University Third Hospital	Beijing	Beijing	China	100191
5	Zhongshan Hospital Xiamen University	Xiamen	Fujian	China	361004
6	Guangzhou First People's Hospital	Guangzhou	Guangdong	China	510180
7	Qingyuan People's Hospital	Qingyuan	Guangdong	China	511518
8	Shenzhen People's Hospital	Shenzhen	Guangdong	China	518020
9	The Second People's Hospital of Shenzhen	Shenzhen	Guangdong	China	518035
10	Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong	China	524000
11	Affiliated Hospital of Guilin Medical College	Guilin	Guangxi	China	541001
12	Affiliated Hospital of Zunyi Medical University	Zunyi	Guizhou	China	563000
13	Affiliated Hospital of Hebei University	Baoding	Hebei	China	071000
14	Luoyang Central Hospital	Luoyang	Henan	China	471009
15	Henan provincial people's hospital	Zhengzhou	Henan	China	450003
16	Hunan Provincial People's Hospital	Changsha	Hunan	China	410005
17	Baotou Central Hospital	Baotou	Inner Mongolia Autonomous Region	China	014000
18	Jiangyin People's Hospital	Jiangyin	Jiangsu	China	214400
19	Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu	China	221006
20	Subei People's Hospital of Jiangsu province	Yangzhou	Jiangsu	China	225001
21	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi	China	330006
22	Huashan Hospital Fudan University	Shanghai	Shanghai	China	200040
23	Chengdu Xinhua Hospital	Chengdu	Sichuan	China	610055
24	Tianjin Chest Hospital	Tianjin	Tianjin	China	300222
25	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang Uygur Autonomous Region	China	830011
26	The First People's Hospital of Kunming (South Hospital)	Kunming	Yunnan	China	650034
27	The First people's Hospital of Kunming	Kunming	Yunnan	China	650034
28	The First People's Hospital of Kunming Ganmei Hospital (North Hospital)	Kunming	Yunnan	China	650224
29	Zhejiang Hospital	Hangzhou	Zhejiang	China	310013
30	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang	China	310014
31	Lishui People's Hospital	Lishui	Zhejiang	China	323000
32	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang	China	317000
33	The 2nd Affiliated Hospital of WMU	Wenzhou	Zhejiang	China	325035
34	Wenzhou Central Hospital	Wenzhou	Zhejiang	China	325099
35	Shanghai Fifth People's Hospital, Fudan University	Shanghai		China	200240