| ID | Type | Description | Link |
|---|---|---|---|
| 2011-003893-97 |
Not provided
Not provided
Not provided
Not provided
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| Name | Class |
|---|---|
| Forest Laboratories | INDUSTRY |
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.
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
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Experimental | IV treatment |
|
| Meropenem | Active Comparator | IV treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAZ-AVI | Drug | Ceftazidime 2000 mg and 500 mg of avibactam |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | The number 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 is necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, death where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA. | TOC: 28 to 35 days after start of study drug |
| Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | The number 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. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. | TOC: 28 to 35 days after start of study drug |
| Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | The number 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. | TOC: 28 to 35 days after start of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | The number 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. | TOC: 28 to 35 days after start of study drug |
Not provided
Inclusion Criteria:
18 to 90 years of age inclusive
Female patient is authorized to participate if at least one of the following criteria are met:
Intraoperative/postoperative enrollment with 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 response; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections
Exclusion Criteria:
Not provided
Not provided
Not provided
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| Name | Affiliation | Role |
|---|---|---|
| Paul Newell, MBBS, MRCP | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chula Vista | California | United States | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26962078 | Background | Mazuski JE, Gasink LB, Armstrong J, Broadhurst H, Stone GG, Rank D, Llorens L, Newell P, Pachl J. Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program. Clin Infect Dis. 2016 Jun 1;62(11):1380-1389. doi: 10.1093/cid/ciw133. Epub 2016 Mar 8. | |
| 37700689 |
Not provided
| ID | Type | URL | Comment |
|---|---|---|---|
| D4280C00001 Revised CSP | Study Protocol | View IPD |
After obtaining written informed consent patients underwent a preliminary evaluation for eligibility within the 24-hour period prior to initiation of IV study therapy. eligible patients were randomized to 1 of 2 treatment groups in a 1:1 ratio according to the central randomization schedule.
Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA. First patient enrolled 22 March 2012 and last patient's last visit was 07 April 2014. Patients were adults hospitalised with complicated intra-abdominal infection (cIAI) that required surgery and IV antibiotics.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | CAZ-AVI + Metronidazole | CAZ (2000mg)/AVI (500mg): IV treatment |
| FG001 | Meropenem | 1000 mg: IV treatment |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
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| Metronidazole |
| Drug |
500 mg of Metronidazole |
|
| Meropenem | Drug | 1 gram of Meropenem |
|
| Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | The number 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. | TOC: 28 to 35 days after start of study drug |
| Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | 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. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. | EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU: 42 to 49 days after start of study drug |
| Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | 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 a surgical review panel (SRP) assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence). | EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU 42 to 49 days after start of study drug |
| Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | The number 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. | TOC: 28 to 35 days after start of study drug. |
| Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | 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. | Test of Cure: 28 to 35 days after start of study drug |
| Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | The number 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. | TOC: 28 to 35 days after start of study drug |
| Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Microbiological 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). | Test of Cure: 28 to 35 days after start of study drug |
| Number of Patients Afebrile at Last Observation in the Clinically Evaluable 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. | Test of Cure: 1 to 14 days after start of study drug |
| 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 | 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 |
| San Diego |
| California |
| United States |
| Research Site | St Louis | Missouri | United States |
| Research Site | Somers Point | New Jersey | United States |
| Research Site | Córdoba | Argentina |
| Research Site | Rosario | Argentina |
| Research Site | Rousse | Bulgaria |
| Research Site | Varna | Bulgaria |
| Research Site | Zagreb | Croatia |
| Research Site | Děčín | Czechia |
| Research Site | Hradec Králové | Czechia |
| Research Site | Jihlava | Czechia |
| Research Site | Olomouc | Czechia |
| Research Site | Prague | Czechia |
| Research Site | Teplice | Czechia |
| Research Site | Budapest | Hungary |
| Research Site | Székesfehérvár | Hungary |
| Research Site | Bangalore | India |
| Research Site | Pune | India |
| Research Site | Trivandrum | India |
| Research Site | Vadodara | India |
| Research Site | Hadera | Israel |
| Research Site | Haifa | Israel |
| Research Site | Riga | Latvia |
| Research Site | Alor Star | Malaysia |
| Research Site | Durango | Mexico |
| Research Site | Guadalajara, Jalisco | Mexico |
| Research Site | Mexico City | Mexico |
| Research Site | 's-Hertogenbosch | Netherlands |
| Research Site | Enschede | Netherlands |
| Research Site | Arequipa | Peru |
| Research Site | Cercardo de Lima | Peru |
| Research Site | Lima | Peru |
| Research Site | Trujillo | Peru |
| Research Site | Cluj-Napoca | Romania |
| Research Site | Iași | Romania |
| Research Site | Kemerovo | Russia |
| Research Site | Moscow | Russia |
| Research Site | Saratov | Russia |
| Research Site | Vsevolozhsk | Russia |
| Research Site | Pretoria | South Africa |
| Research Site | Alcorcón | Spain |
| Research Site | Elche | Spain |
| Research Site | Sabadell(Barcelona) | Spain |
| Research Site | Kaohsiung City | Taiwan |
| Research Site | Taichung | Taiwan |
| Research Site | Tainan | Taiwan |
| Research Site | Taipei | Taiwan |
| Research Site | Bangkok | Thailand |
| Research Site | Khon Kaen | Thailand |
| Research Site | Phisanulok | Thailand |
| Research Site | Dnipropetrovsk | Ukraine |
| Research Site | Ivano-Frankivsk | Ukraine |
| Research Site | Kharkiv | Ukraine |
| Research Site | Kyiv | Ukraine |
| Research Site | Zaporizhzhya | Ukraine |
| Derived |
| 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. |
| 32602065 | Derived | 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. |
| 31890160 | Derived | Kongnakorn T, Eckmann C, Bassetti M, Tichy E, Di Virgilio R, Baillon-Plot N, Charbonneau C. Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI). Antimicrob Resist Infect Control. 2019 Dec 21;8:204. doi: 10.1186/s13756-019-0652-x. eCollection 2019. |
| 30221827 | Derived | 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. |
| 30061279 | Derived | 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. |
| 29912399 | Derived | 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. |
| 29686147 | Derived | Stone GG, Newell P, Bradford PA. In Vitro Activity of Ceftazidime-Avibactam against Isolates from Patients in a Phase 3 Clinical Trial for Treatment of Complicated Intra-abdominal Infections. Antimicrob Agents Chemother. 2018 Jun 26;62(7):e02584-17. doi: 10.1128/AAC.02584-17. Print 2018 Jul. |
| 28348155 | Derived | Mendes RE, Castanheira M, Woosley LN, Stone GG, Bradford PA, Flamm RK. Molecular beta-Lactamase Characterization of Aerobic Gram-Negative Pathogens Recovered from Patients Enrolled in the Ceftazidime-Avibactam Phase 3 Trials for Complicated Intra-abdominal Infections, with Efficacies Analyzed against Susceptible and Resistant Subsets. Antimicrob Agents Chemother. 2017 May 24;61(6):e02447-16. doi: 10.1128/AAC.02447-16. Print 2017 Jun. |
RECLAIM 1 (D4280C00001) Revised Clinical Study Protocol |
| COMPLETED |
|
| NOT COMPLETED |
|
|
The MITT analysis set includes all patients who met the disease definition for cIAI and received at least 1 dose of study drug. 15 patients excluded received at least one dose of study drug but failed the minimum disease criteria.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | CAZ-AVI + Metronidazole | CAZ (2000mg)/AVI (500mg): IV treatment |
| BG001 | Meropenem | 1000 mg: IV treatment |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | The number 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 is necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, death where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA. | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug |
|
|
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | The number 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. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. | The MITT analysis set included all randomized patients who met the disease definition of cIAI and who received any amount of study drug. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | The number 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. | The CE analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | The number 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. | ME analysis set defined as all patients included in the CE set with at least 1 Gram negative, aerobic, susceptible pathogen in the initial/prestudy culture. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | The number 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. | Extended ME analysis set defined as all patients included in the CE set with at least 1 Gram negative, aerobic, pathogen in the initial/prestudy culture, regardless of susceptibility. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | 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. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU: 42 to 49 days after start of study drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | 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 a surgical review panel (SRP) assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence). | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU 42 to 49 days after start of study drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | The number 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. | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | 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. | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | Test of Cure: 28 to 35 days after start of study drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | The number 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. | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | TOC: 28 to 35 days after start of study drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Microbiological 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). | The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded. | Posted | Number | Participants | Test of Cure: 28 to 35 days after start of study drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients Afebrile at Last Observation in the Clinically Evaluable 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. | Clinically evaluable (CE) with fever, defined as >38ºC at study entry. | Posted | Number | Participants | Test of Cure: 1 to 14 days after start of study drug |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | PK analysis set | Posted | Geometric Mean | Full Range | (NG/ML) | 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 |
|
Adverse event data were collected from the screening/consent visit until the late follow-up visit (ie Day -1/0 to Day 42).
AEs spontaneously reported by the patient or care provider or reported in response to the open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CAZ-AVI + Metronidazole | CAZ (2000mg)/AVI (500mg): IV treatment. | 17 | 529 | 184 | 529 | ||
| EG001 | Meropenem | 1000 mg: IV treatment | 15 | 529 | 152 | 529 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | (MedDRA) | Systematic Assessment |
| |
| Transaminases increased | Investigations | (MedDRA) | Systematic Assessment |
| |
| Gastrointestinal stoma necrosis | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Abdominal abscess | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Bronchopneumonia | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Candida sepsis | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | (MedDRA) | Systematic Assessment |
| |
| Colonic abscess | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Empyema | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Enterococcal bacteraemia | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Septic enceohalopathy | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Systematic candida | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Adenocarcinoma gastric | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | (MedDRA) | Systematic Assessment |
| |
| Bone marrow failure | Blood and lymphatic system disorders | (MedDRA) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | (MedDRA) | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | (MedDRA) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | (MedDRA) | Systematic Assessment |
| |
| Delirium tremens | Psychiatric disorders | (MedDRA) | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | (MedDRA) | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | (MedDRA) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Left ventricular failure | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Right ventricular failure | Cardiac disorders | (MedDRA) | Systematic Assessment |
| |
| Shock | Vascular disorders | (MedDRA) | Systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Colonic fistula | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Gastrointestinal hypomotility | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Ileal perforation | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Localised intraabdominal fluid collection | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Small intestine perforation | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Volvulus | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | (MedDRA) | Systematic Assessment |
| |
| Biloma | Hepatobiliary disorders | (MedDRA) | Systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | (MedDRA) | Systematic Assessment |
| |
| Critical illness myopathy | Musculoskeletal and connective tissue disorders | (MedDRA) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | (MedDRA) | Systematic Assessment |
| |
| Multi-organ failure | General disorders | (MedDRA) | Systematic Assessment |
| |
| Sudden death | General disorders | (MedDRA) | Systematic Assessment |
| |
| Abdominal wound dehiscence | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Anastomotic leak | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Gastrointestinal stoma complication | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Pneumothorax traumatic | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Post procedural bile leak | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Postoperative wound complication | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Suture related complication | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Wound dehiscence | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
| |
| Wound evisceration | Injury, poisoning and procedural complications | (MedDRA) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wound infection | Infections and infestations | (MedDRA) | Systematic Assessment |
| |
| Headache | Nervous system disorders | (MedDRA) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | (MedDRA) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | (MedDRA) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | (MedDRA) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Pyrexia | General disorders | (MedDRA) | Systematic Assessment |
| |
| Asthenia | General disorders | (MedDRA) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | (MedDRA) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | (MedDRA) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | (MedDRA) | Systematic Assessment |
|
This summary describes data collected from two identical CSPs (D4280C00001 and D4280C00005). With agreement from the EMA and the FDA the data have been combined into a single study database.
The PI shall not publish results until the earliest of (i) date of the 1st study publication (joint between PI, sponsor and study sites) (ii) 18 months after study completion, or (iii) sponsor notification that no multi-center publication is to be made. The PI submits the publication for review 60 days before submission. Sponsor may embargo for a further 90 days to protect IP rights. Sponsor may request removal of confidential and/or proprietry information.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul Newell, Medical Science Director | AstraZeneca | +44 1625 515727 | paul.newell@astrazeneca.com |
| ID | Term |
|---|---|
| D008795 | Metronidazole |
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
| Male |
|
| Indeterminate |
|
|
|
|
|
|
|
|
| CAZ-AVI + Metronidazole (TOC) |
TOC - 28 to 35 days after start of study drug |
| OG003 | Meropenem (TOC) | TOC - 28 to 35 days after start of study drug |
| OG004 | CAZ-AVI + Metronidazole (LFU) | LFU - 42 to 49 days after start of study drug |
| OG005 | Meropenem (LFU) | LFU - 42 to 49 days after start of study drug |
|
|
EOT - within 24 hours after last dose of study drug
| OG002 | CAZ-AVI + Metronidazole (TOC) | TOC - 28 to 35 days after start of study drug |
| OG003 | Meropenem (TOC) | TOC - 28 to 35 days after start of study drug |
| OG004 | CAZ-AVI + Metronidazole (LFU) | LFU - 42 to 49 days after start of study drug |
| OG005 | Meropenem (LFU) | LFU - 42 to 49 days after start of study drug |
|
|
| OG003 | Meropenem (Denominator) | Number of patients with pathogen at baseline |
|
|
Number of patients with pathogen at baseline
|
|
| Meropenem (Denominator) |
Number of patients with pathogen at baseline |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| OG005 | AVI (3) | 300-360 mins after dose |
|
|