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NCT00752219

Prospective Multicenter Doubleblind Randomized Study of NXL104/Ceftazidime + Metronidazole vs. Meropenem in Treatment of Complicated Intra-abdominal Infections

Completed Phase 2 Results posted Last updated 3 July 2018
What this trial tests

Phase 2 trial testing ceftazidime/NXL104 + metronidazole in Complicated Intra-abdominal Infections in 204 participants. Completed in 31 December 2009.

Timeline
31 March 2009
Primary endpoint
30 November 2009
31 December 2009

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment204
Start date31 March 2009
Primary completion30 November 2009
Estimated completion31 December 2009
Sites45 locations across France, Russia, Poland, Romania, Bulgaria, Lebanon, United States, India

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 65, any sex, with Complicated Intra-abdominal Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Clinical Response at the Test of Cure (TOC) Visit Primary · Test of cure visit: 2 weeks post-therapy (Day 28)

Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were microbiologically evaluable (ME) at baseline.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole62
Meropenem71
Number of Participants With Clinical Response at the End of Intravenous (IV) Therapy Secondary · End of IV therapy: From Day 5 to Day 14

Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole66
Meropenem74
Number of Participants With Clinical Response at the Late Follow-up Visit Secondary · Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks)

Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole62
Meropenem71
Number of Participants With Microbiological Response at the Test of Cure Visit Secondary · Test of cure visit: 2 weeks post-therapy (Day 28)

Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole62
Meropenem71
Number of Participants With Microbiological Response at the End of IV Therapy Secondary · End of IV therapy: From Day 5 to Day 14

Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole66
Meropenem74
Number of Participants With Microbiological Response at the Late Follow-up Visit Secondary · Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks)

Favorable: eradication (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication (absence of material to culture in a patient who had responded clinically to treatment)

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole62
Meropenem71
Number of Participants With Clinical Response in Clinically Evaluable (CE) Participants at the Test of Cure Visit Secondary · Test of cure visit: 2 weeks post-therapy (Day 28)

Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole80
Meropenem85
Number of Participants With Clinical Response in CE Participants at the End of IV Therapy Secondary · End of IV therapy: From Day 5 to Day 14

Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole84
Meropenem87
Number of Participants With Clinical Response in CE Participants at the Late Follow-up Visit Secondary · Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks)

Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required.

GroupValue95% CI
NXL104/Ceftazidime + Metronidazole79
Meropenem84
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · Baseline up to 6 weeks after last dose of study treatment (up to a maximum of 8 weeks)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 weeks after last dose of study treatment that were absent before treatment or that worsened relative to p

AEs
GroupValue95% CI
NXL104/Ceftazidime + Metronidazole65
Meropenem59
SAEs
GroupValue95% CI
NXL104/Ceftazidime + Metronidazole9
Meropenem11

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NXL104/Ceftazidime + Metronidazole
Serious: 9/101 (9%)
Deaths:
Meropenem
Serious: 11/102 (11%)
Deaths:

Serious adverse events (20 terms)

ReactionSystemNXL104/Ceftazidime + Metro…Meropenem
Intestinal ObstructionGastrointestinal disorders
Atrial FibrillationCardiac disorders
Cardiac ArrestCardiac disorders
Gastric PerforationGastrointestinal disorders
Localised Intraabdominal Fluid CollectionGastrointestinal disorders
PeritonitisGastrointestinal disorders
VolvulusGastrointestinal disorders
Multi-Organ FailureGeneral disorders
PneumoniaInfections and infestations
Postoperative AbscessInfections and infestations
SepsisInfections and infestations
Septic ShockInfections and infestations
Wound SecretionInjury, poisoning and procedural complications
Hepatic Enzyme IncreasedInjury, poisoning and procedural complications
Platelet Count DecreasedInjury, poisoning and procedural complications
Diabetes MellitusMetabolism and nutrition disorders
Renal Failure AcuteRenal and urinary disorders
Respiratory DisorderRespiratory, thoracic and mediastinal disorders
Respiratory DistressRespiratory, thoracic and mediastinal disorders
Tracheo-Oesophageal FistulaRespiratory, thoracic and mediastinal disorders
Other adverse events (11 terms — click to expand)

ReactionSystemNXL104/Ceftazidime + Metro…Meropenem
Aspartate Aminotransferase IncreasedGeneral disorders
VomitingGastrointestinal disorders
Alanine Aminotransferase IncreasedGeneral disorders
PyrexiaGeneral disorders
NauseaGastrointestinal disorders
Blood Alkaline Phosphatase IncreasedGeneral disorders
Abdominal PainGastrointestinal disorders
Platelet Count IncreasedGeneral disorders
White Blood Cell Count IncreasedGeneral disorders
HaematuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Intestinal Obstruction, Atrial Fibrillation, Cardiac Arrest, Gastric Perforation, Localised Intraabdominal Fluid Collection, Peritonitis, Volvulus, Multi-Organ Failure.

Data from ClinicalTrials.gov NCT00752219 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether NXL104 plus ceftazidime is effective in the treatment of complicated intra-abdominal infections as compared to a comparator group.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches.
    Karaiskos I, Giamarellou H. · · 2014 · cited 212× · PMID 24766095 · DOI 10.1517/14656566.2014.914172
  2. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial.
    Lucasti C, Popescu I, Ramesh MK, Lipka J, et al · · 2013 · cited 185× · PMID 23391714 · DOI 10.1093/jac/dks523
  3. New β-Lactamase Inhibitors in the Clinic.
    Papp-Wallace KM, Bonomo RA. · · 2016 · cited 121× · PMID 27208767 · DOI 10.1016/j.idc.2016.02.007
  4. Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy?
    Perez F, El Chakhtoura NG, Papp-Wallace KM, Wilson BM, et al · · 2016 · cited 112× · PMID 26799840 · DOI 10.1517/14656566.2016.1145658
  5. Comparative in vitro and in vivo efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa.
    Crandon JL, Schuck VJ, Banevicius MA, Beaudoin ME, et al · · 2012 · cited 93× · PMID 22985878 · DOI 10.1128/aac.00851-12
  6. Dose Selection and Validation for Ceftazidime-Avibactam in Adults with Complicated Intra-abdominal Infections, Complicated Urinary Tract Infections, and Nosocomial Pneumonia.
    Das S, Li J, Riccobene T, Carrothers TJ, et al · · 2019 · cited 54× · PMID 30670413 · DOI 10.1128/aac.02187-18
  7. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa.
    Nichols WW, Stone GG, Newell P, Broadhurst H, et al · · 2018 · cited 28× · PMID 30061279 · DOI 10.1128/aac.02590-17
  8. β-Lactamase Characterization of Gram-Negative Pathogens Recovered from Patients Enrolled in the Phase 2 Trials for Ceftazidime-Avibactam: Clinical Efficacies Analyzed against Subsets of Molecularly Characterized Isolates.
    Mendes RE, Castanheira M, Gasink L, Stone GG, et al · · 2015 · cited 21× · PMID 26666936 · DOI 10.1128/aac.01173-15

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