Complicated Intra-abdominal InfectionPhase 3RECLAIM3NCT01726023
Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for Hospitalized Adults With Complicated Intra-Abd Infections
A Phase 3 study testing Ceftazidime-avibactam, metronidazole and Meropenem in people with Complicated Intra-abdominal Infection, run by Pfizer at 30 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Complicated Intra-abdominal Infection
- What is being tested?
- Ceftazidime-avibactam, metronidazole and Meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 486 participants
- Where
- 30 sitesin 3 countries
- Study dates
- Jan 2013to Mar 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
30 sites in 3 countries.
30 sites in 3 countries
China19 sites
Research Site
Baotou
Research Site
Beijing
Research Site
Changsha
Research Site
Chengdu
Research Site
Chongqing
Research Site
Fuzhou
Research Site
Guangzhou
Research Site
Guilin
Research Site
Haikou
Research Site
Hebei
Research Site
Jiangyin
Research Site
Liaocheng
Research Site
Nanchang
Research Site
Shanghai
Research Site
Tianjin
Research Site
Ürümqi
Research Site
Wenzhou
Research Site
Wuxi
Research Site
Xi'an
South Korea9 sites
Research Site
Ansan-si
Research Site
Anyang-si
Research Site
Busan
Research Site
Cheongju-si
Research Site
Daejeon
Research Site
Gwangju
Research Site
Jinju
Research Site
Seoul
Research Site
Wŏnju
About this study
Official title: A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults
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.
Read the detailed description
A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults
- Conditions
- Complicated Intra-abdominal Infection
- Being tested
- Ceftazidime-avibactam, metronidazole, Meropenem
- Keywords
- Ceftazidime-avibactam,, Metronidazole,, Meropenem,, Anti-Bacterial Agents,, Anti-Infective Agents,, Therapeutic Uses,, Pharmacologic Actions,, Physiological Effects of Drugs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftazidime-avibactamDrug
Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg
metronidazoleDrug
Metronidazole 500mg/100ml solution for infusion
MeropenemDrug
Meropenem powder for solution for infusion 1000mg
| Study group | Role | What they receive |
|---|---|---|
| Ceftazidime-Avibactam plus metronidazole | Experimental | Not described Receives: Drug: Ceftazidime-avibactam; Drug: metronidazole |
| Meropenem | Active comparator | Not described Receives: Drug: Meropenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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 Extended Microbiologically Evaluable (ME) 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.
Measured: 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 Microbiological Modified Intent-to-treat (mMITT) 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.
Measured: 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 Microbiological Modified Intent-to-treat (mMITT) 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.
Measured: 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 Microbiological Modified Intent-to-treat (mMITT) 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.
Measured: 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 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.
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) 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.
Measured: At late follow up (LFU) visits (Day 42 to 49)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated".
Measured: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
The proportion of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Measured: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
The microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiologically Evaluable (ME) Analysis Set.
The microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Measured: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Extended Microbiologically Evaluable (ME) Analysis Set.
The microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Measured: At the test of cure (TOC) (Day 28 to 35)
The Time to First Defervescence in the Clinically Evaluable (CE) Analysis Set for Patients Who Have Fever at Study Entry.
Time to first defervescence was calculated for patients with a fever (>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. Time to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.
Measured: while on study therapy (from Day 1 to Day 14)
The Time to First Defervescence in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set for Patients Who Have Fever at Study Entry.
Time to first defervescence was calculated for patients with a fever (>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. Time to first defervescence while on IV study therapy in the CE analysis set at TOC for patients who had fever at study entry is defined as time (in days) from the first dose of IV study therapy to first absence of fever.
Measured: while on study therapy (from Day 1 to Day 14)
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality.
Adverse event data were collected from the screening/consent visit until the late follow-up visit (i.e. Day -1/0 to Day 42).
Measured: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability by Incidence: Extent of Exposure.
Duration of exposure is calculated as the difference between the last study therapy date and the first study therapy date converted to days plus 1 day. Actual calculated duration could be shorter or longer than a full day.
Measured: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability: Clinical Laboratory Evaluation Hematology.
Potentially clinically significant (PCS) post Baseline hematology values up to LFU (Safety analysis set)
Measured: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry.
Potentially clinically significant (PCS) post Baseline clinical chemistry values up to LFU (Safety analysis set)
Measured: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability:ECG , QTcB and QTcF Intervals
Shifts in ECG interpretation and changes in QT, QTcB, and QTcF intervals , from baseline to post baseline.
Measured: EOT visit/any observation on treatment
Plasma Concentrations for Ceftazidime and Avibactam
Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations
Measured: At Day 3: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Complicated Intra-abdominal InfectionStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 486 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul A Newell, MBBS, MRCP, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01726023
- Sponsor's protocol ID
- D4280C00018
- Other IDs
- 2011-003893-97
- Acronym
- RECLAIM3
- Status last verified
- Sep 2017
- First submitted
- 5 Nov 2012
- Last updated
- 6 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 37700689Cheng 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.
PubMed 32602065Li 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.
PubMed 30221827Nichols 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.
PubMed 30061279Stone 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.
PubMed 29912399Qin 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.
PubMed 28363526
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults
- ClinicalTrials.gov ID
- NCT01726023
- Acronym / sponsor ID
- RECLAIM3 / D4280C00018
- Conditions
- Complicated Intra-abdominal Infection
- Keywords
- Ceftazidime-avibactam,, Metronidazole,, Meropenem,, Anti-Bacterial Agents,, Anti-Infective Agents,, Therapeutic Uses,, Pharmacologic Actions,, Physiological Effects of Drugs
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 486 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jan 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 14 Nov 2012 (estimated)
- Results
- Posted 14 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ceftazidime-Avibactam plus metronidazole | Experimental | Drug: Ceftazidime-avibactam, Drug: metronidazole |
| Meropenem | Active comparator | Drug: Meropenem |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ceftazidime-avibactamCeftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg | Drug | Ceftazidime-Avibactam plus metronidazole |
| metronidazoleMetronidazole 500mg/100ml solution for infusion | Drug | Ceftazidime-Avibactam plus metronidazole |
| MeropenemMeropenem powder for solution for infusion 1000mg | Drug | Meropenem |
Primary outcome
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set.
Time frame: At the test of cure visit (Day 28 to35)
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.
40 secondary outcomes
The Proportion of Patients With Clinical Cure at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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 Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: 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 Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: 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 Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: 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 Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: 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 Clinically Evaluable (CE) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With Clinical Cure at the Late Follow up (LFU) Visit in the Clinically Evaluable (CE) Analysis Set.
Time frame: At late follow up (LFU) visits (Day 42 to 49)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per-patient Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Favorable Per-pathogen Microbiological Response in the Microbiological Response at the Late Follow up (LFU) Visit in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Favorable Per-pathogen Microbiological Response at the End of Treatment (EOT) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the end of treatment (EOT) (within 24 hours after last IV dose)
The Proportion of Favorable Per-pathogen Microbiological Response at the Test of Cure (TOC) Visit in the Extended Microbiologically Evaluable(ME) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Favorable Per-pathogen Microbiological Response at the Late Follow up (LFU) Visit in the Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the late follow up (LFU) (Day 42 to 49)
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Proportion of Patients With a Favorable Per Patient Microbiological Response at the Test of Cure (TOC) Visit for Patients Infected With Ceftazidime Resistant Pathogens in the Extended Microbiologically Evaluable (ME) Analysis Set.
Time frame: At the test of cure (TOC) (Day 28 to 35)
The Time to First Defervescence in the Clinically Evaluable (CE) Analysis Set for Patients Who Have Fever at Study Entry.
Time frame: while on study therapy (from Day 1 to Day 14)
The Time to First Defervescence in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set for Patients Who Have Fever at Study Entry.
Time frame: while on study therapy (from Day 1 to Day 14)
Safety and Tolerability by Incidence and Severity of Adverse Events and Serious Adverse Events and Mortality.
Time frame: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability by Incidence: Extent of Exposure.
Time frame: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability: Clinical Laboratory Evaluation Hematology.
Time frame: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability: Clinical Laboratory Evaluation Clinical Chemistry.
Time frame: study duration (from screening to Day 49 LFU visit)
Safety and Tolerability:ECG , QTcB and QTcF Intervals
Time frame: EOT visit/any observation on treatment
Plasma Concentrations for Ceftazidime and Avibactam
Time frame: At Day 3: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37700689Torres 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.
- Derived from this study: PubMed 32602065Cheng 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.
- Derived from this study: PubMed 30221827Li 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.
- Derived from this study: PubMed 30061279Nichols 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.
- Derived from this study: PubMed 29912399Stone 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.
- Derived from this study: PubMed 28363526Qin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul A Newell, MBBS, MRCP study director
AstraZeneca
30 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ceftazidime-avibactam, metronidazole and Meropenem in people with Complicated Intra-abdominal Infection, run by Pfizer at 30 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in China, South Korea, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Patients With Clinical Cure at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) Analysis Set. (time frame: At the test of cure visit (Day 28 to35)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01726023, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2017.