NCT01726023

Brief Summary

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam plus Metronidazole compared to Meropenem for treating hospitalized patients with complicated intra-abdominal infections.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
486

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2013

Geographic Reach
3 countries

30 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2012

Completed
9 days until next milestone

First Posted

Study publicly available on registry

November 14, 2012

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2013

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

April 14, 2016

Completed
Last Updated

September 6, 2017

Status Verified

September 1, 2017

Enrollment Period

2.2 years

First QC Date

November 5, 2012

Results QC Date

February 1, 2016

Last Update Submit

September 1, 2017

Conditions

Keywords

Ceftazidime-avibactam,Metronidazole,Meropenem,Anti-Bacterial Agents,Anti-Infective Agents,Therapeutic Uses,Pharmacologic Actions,Physiological Effects of Drugs

Outcome Measures

Primary Outcomes (1)

  • The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set.

    The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.

    At the test of cure visit (Day 28 to35)

Secondary Outcomes (40)

  • The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.

    At the end of treatment (EOT) (within 24 hours after last IV dose)

  • The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.

    At the test of cure (TOC) (Day 28 to 35)

  • The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.

    At the late follow up (LFU) (Day 42 to 49)

  • The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.

    At the end of treatment (EOT) (within 24 hours after last IV dose)

  • The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.

    At the test of cure (TOC) (Day 28 to 35)

  • +35 more secondary outcomes

Study Arms (2)

Ceftazidime-Avibactam plus metronidazole

EXPERIMENTAL
Drug: Ceftazidime-avibactamDrug: metronidazole

Meropenem

ACTIVE COMPARATOR
Drug: Meropenem

Interventions

Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg

Ceftazidime-Avibactam plus metronidazole

Metronidazole 500mg/100ml solution for infusion

Ceftazidime-Avibactam plus metronidazole

Meropenem powder for solution for infusion 1000mg

Meropenem

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient must be 18 to 90 years of age, inclusive,
  • Female patients can participate if they are surgically sterilized or postmenopausal for at least 1 year or her sexual partner has had a vasectomy
  • Female of childbearing potential has had normal menstrual periods for 3 months and negative serum pregnancy test and agree to practice highly effective methods of birth control during treatment and for at least 7 days after last dose
  • Intraoperative/postoperative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis
  • Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory indicators; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections

You may not qualify if:

  • Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious
  • Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation
  • Patients whose surgery will include staged abdominal repair, or "open abdomen" technique, or marsupialization
  • Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis
  • Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

Research Site

Baotou, China

Location

Research Site

Beijing, China

Location

Research Site

Changsha, China

Location

Research Site

Chengdu, China

Location

Research Site

Chongqing, China

Location

Research Site

Fuzhou, China

Location

Research Site

Guangzhou, China

Location

Research Site

Guilin, China

Location

Research Site

Haikou, China

Location

Research Site

Hebei, China

Location

Research Site

Jiangyin, China

Location

Research Site

Liaocheng, China

Location

Research Site

Nanchang, China

Location

Research Site

Shanghai, China

Location

Research Site

Tianjin, China

Location

Research Site

Ürümqi, China

Location

Research Site

Wenzhou, China

Location

Research Site

Wuxi, China

Location

Research Site

Xi'an, China

Location

Research Site

Ansan-si, South Korea

Location

Research Site

Anyang-si, South Korea

Location

Research Site

Busan, South Korea

Location

Research Site

Cheongju-si, South Korea

Location

Research Site

Daejeon, South Korea

Location

Research Site

Gwangju, South Korea

Location

Research Site

Jinju, South Korea

Location

Research Site

Seoul, South Korea

Location

Research Site

Wŏnju, South Korea

Location

Research Site

Hanoi, Vietnam

Location

Research Site

Hochiminh, Vietnam

Location

Related Publications (6)

  • Torres A, Wible M, Tawadrous M, Irani P, Stone GG, Quintana A, Debabov D, Burroughs M, Bradford PA, Kollef M. Efficacy and safety of ceftazidime/avibactam in patients with infections caused by beta-lactamase-producing Gram-negative pathogens: a pooled analysis from the Phase 3 clinical trial programme. J Antimicrob Chemother. 2023 Nov 6;78(11):2672-2682. doi: 10.1093/jac/dkad280.

  • Cheng K, Newell P, Chow JW, Broadhurst H, Wilson D, Yates K, Wardman A. Safety Profile of Ceftazidime-Avibactam: Pooled Data from the Adult Phase II and Phase III Clinical Trial Programme. Drug Saf. 2020 Aug;43(8):751-766. doi: 10.1007/s40264-020-00934-3.

  • Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.

  • Nichols WW, Stone GG, Newell P, Broadhurst H, Wardman A, MacPherson M, Yates K, Riccobene T, Critchley IA, Das S. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e02590-17. doi: 10.1128/AAC.02590-17. Print 2018 Nov.

  • Stone GG, Newell P, Gasink LB, Broadhurst H, Wardman A, Yates K, Chen Z, Song J, Chow JW. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.

  • Qin X, Tran BG, Kim MJ, Wang L, Nguyen DA, Chen Q, Song J, Laud PJ, Stone GG, Chow JW. A randomised, double-blind, phase 3 study comparing the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem for complicated intra-abdominal infections in hospitalised adults in Asia. Int J Antimicrob Agents. 2017 May;49(5):579-588. doi: 10.1016/j.ijantimicag.2017.01.010. Epub 2017 Mar 29.

MeSH Terms

Interventions

avibactam, ceftazidime drug combinationMetronidazoleMeropenem

Intervention Hierarchy (Ancestors)

NitroimidazolesNitro CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsThienamycinsCarbapenemsbeta-LactamsLactamsAmidesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Results Point of Contact

Title
David Wilson, Statistical Team Leader - Infection
Organization
AstraZeneca

Study Officials

  • Paul A Newell, MBBS, MRCP

    AstraZeneca

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2012

First Posted

November 14, 2012

Study Start

January 1, 2013

Primary Completion

March 1, 2015

Study Completion

March 1, 2015

Last Updated

September 6, 2017

Results First Posted

April 14, 2016

Record last verified: 2017-09

Locations