A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ104) Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra Abdominal Infections (cIAI) in Hospitalized Adults
- Conditions
- Complicated Intra-Abdominal Infection (cIAI)MedDRA version: 14.1Level: LLTClassification code 10056570Term: Intra-abdominal infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2011-003895-35-IT
- Lead Sponsor
- ASTRAZENECA AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1066
For inclusion in the study patients should fulfill the following criteria: 1. Patient must provide a signed written informed consent prior to any study-specific procedures. However, if a patient is unable, the patient’s legally acceptable representative may provide written consent, as approved by the institutional-specific guidelines. Those patients who are unconscious or considered by the investigator to be clinically unable to consent at Screening and who are entered into the study by the consent of a legally acceptable representative, should provide their own written informed consent for continuing to participate in the study as soon as possible on recovery, as applicable in accordance with local regulations. 2. Patient must be 18 to 90 years of age inclusive. 3. Women are authorized to participate if they meet the following criteria: (a) Surgical sterilization or (b) Completed menopause, as defined by criteria in footnote1 (If criteria not met, should be regarded as having childbearing potential) OR (c) Female patient capable of having children and agrees not to attempt pregnancy while receiving IV study therapy and for a period of 1 week after. Acceptable methods of contraception for this study are: • Prior to and during the study, use of an intrauterine device, regular depo-progesterone injections, or sexual intercourse with only vasectomized partners • Complete sexual abstinence for the recommended period. EITHER: Intra-operative/postoperative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis. Surgical intervention includes open laparotomy, percutaneous drainage of an abscess, or laparoscopic surgery. Specimens from the surgical intervention must be sent for culture. The patient must have one of the following diagnoses: (a) Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond the gallbladder wall (b) Diverticular disease with perforation or abscess (c) Appendiceal perforation or peri-appendiceal abscess (d) Acute gastric or duodenal perforations, only if operated on >24 hours after perforation occurs (e) Traumatic perforation of the intestines, only if operated on >12 hours after perforation occurs (f) Secondary peritonitis (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites) (g) Intra-abdominal abscess (including of liver or spleen provided that there is extension beyond the organ with evidence of intraperitoneal involvement) OR Preoperative enrollment where the following clinical criteria are met with confirmation of infection by surgical intervention within 24 hours of entry: (a) Requirement for surgical intervention, defined per protocol as open laparotomy, percutaneous drainage of an abscess, or laparoscopic surgery (b) Evidence of systemic inflammatory response, with at least one of the following: - Fever (defined as body temperature >38°C) or hypothermia with a core body temperature <35°C - Elevated white blood cells (>12000 cells/mm3) - Drop in blood pressure (BP) (however, systolic BP must be >90 mm Hg without pressor support) - Increased heart rate( >90 bpm) and respiratory rate (RR) (>20 breaths/min) - Hypoxia - Altered mental status. (c) Physical findings consistent with intra-abdominal infection, such as: - Abdominal pain and/or tenderness, with or without rebound - Localized or diffuse abdominal
Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. 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 the primary etiology is not likely to be infectious. 2. Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation. 3. Patient has simple cholecystitis, or gangrenous cholecystitis without rupture, or simple appendicitis, or acute suppurative cholangitis; or infected necrotizing pancreatitis or pancreatic abscess. 4. Patient’s surgery will include staged abdominal repair, or open abdomen” technique, or marsupialization. Patient is known at study entry to have a cIAI caused by pathogens resistant to the study antimicrobial agents. 6. Patient needs effective concomitant systemic antibacterials (oral, IV, or intramuscular) or antifungals in addition to those designated in the 2 study groups, except vancomycin, linezolid, or daptomycin if started for known or suspected methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus species as per protocol Section 5.6. 7. Patient has evidence of sepsis with shock not responding to IV fluid challenge or anticipated to require the administration of vasopressors for >12 hours. 8. Patient has perinephric infections. 9. Patient has indwelling peritoneal dialysis catheter. 10. Patient has suspected intra-abdominal infections due to fungus, parasites (eg, amebic liver abscess), virus, or tuberculosis. 11. Patient has a known history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to carbapenem or cephalosporin antibiotics or other ß lactam antibiotics or metronidazole. 12. Patient has any of the following laboratory values as defined below: (a) Estimated creatinine clearance =30 mL/min calculated by Cockcroft-Gault method (Cockcroft and Gault 1976). Refer to Appendix E for calculation information. (b) Hematocrit <25% or hemoglobin <8 g/dL (c) Absolute neutrophil count <1000/mm3 (d) Platelet count <75000/mm3 (e) Bilirubin >3 × the upper limit of normal (ULN), unless isolated hyperbilirubinemia is directly related to the acute infection or known Gilbert’s disease (f) ALT or AST >3 × ULN values at Screening. Patients with elevations of AST and/or ALT up to 5 × ULN are eligible if these elevations are acute and directly related to the infectious process being treated. This must be documented. (g) Alkaline phosphatase >3 × ULN. Patients with values >3.0 × ULN and <5.0 × ULN are eligible if this value is acute and directly related to the infectious process being treated. This must be documented. 13. Patient has a body mass index >45 kg/m2. Patient has APACHE II score >30 (see Appendix F). 15. Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness. 16. Patient is unlikely to respond to 5 to 14 days of treatment with antibiotics. 17. Patient has received systemic antibacterial agents within the 72-hour period prior to study entry, unless either of the following pertains: (a) Patient has a new infection (not considered a treatment failure) and both of the following are met: - Patient received no more than 24 hours of total prior antibiotic therapy - Patient received =1 dose of a treatment regimen postopera
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method