Complicated Intra-Abdominal Infection (cIAI) MedDRA version: 18.0 Level: LLT Classification code 10056570 Term: Intra-abdominal infection System Organ Class: 100000004862
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must be =3 calendar months to 38.5°C, or equivalent to method used) or hypothermia (with a core body or rectal temperature 15000 cells/mm3) ? C-reactive protein (CRP) levels (>10 mg/L) (c) Physical Findings consistent with intra-abdominal infection, such as: ? Abdominal pain and/or tenderness ? Localised or diffuse abdominal wall rigidity ? Abdominal mass (d) Intention to send specimens from the surgical intervention for culture (e) (Optional) Supportive radiologic findings of intra-abdominal infection, such as perforated intraperitoneal abscess detected on: ? Computed tomography (CT) scan or ? Magnetic resonance imaging (MRI) or ? Ultrasound or (ii) Intra-operative/postoperative enrolment inclusion: Visual confirmation of intra-abdominal infection associated with peritonitis at laparotomy, laparoscopy or percutaneous drainage (to be confirmed pending feasibility); must have one of these diagnoses: (a) Appendiceal
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous enrolment or randomisation in the present study 3. Participation in another clinical study with an investigational product (IP) during the last 30 days before the first dose of IV study drug or have previously participated in the current study or in another study of CAZ-AVI (in which an active agent was received) 4. History of hypersensitivity reactions to carbapenems, cephalosporins, penicillin, other ß lactam antibiotics or metronidazole 5. Concurrent infection, that may interfere with the evaluation of response to the study antibiotics at the time of randomisation 6. Patient needs effective concomitant systemic antibacterials (oral, IV, or intramuscular) in addition to those designated in the 2 study groups(CAZ-AVI plus metronidazole group or meropenem group) (see Section 7.8) 7. Receipt of non-study systemic antibiotic therapy for cIAI for more than 24 hours immediately preceding the start of the infusion of the first dose of IV study drug therapy, except in proven resistant organisms and or worsening of the clinical condition 8. Patient is considered unlikely to survive the 6 to 8 week study period 9. Patient is unlikely to respond to 7 to 15 days of treatment with antibiotics 10. Patient is receiving haemodialysis or peritoneal dialysis 11. Diagnosis of abdominal wall abscess confined to musculature of the abdominal wall or ischaemic bowel disease without perforation, traumatic bowel perforation requiring surgery within 12 hours of perforation, or perforation of gastroduodenal ulcers requiring surgery within 24 hours of perforation (these are considered situations of peritoneal soiling before the infection has become established) 12. Simple (uncomplicated), non-perforated appendicitis or gangrenous appendicitis without rupture into the peritoneal cavity identified during a surgical procedure OR presence of primary peritonitis (ie, spontaneous bacterial peritonitis) or peritonitis associated with cirrhosis or chronic ascites 13. At the time of randomisation, patient is known to have a cIAI caused by pathogens resistant to the study antimicrobials planned to be used in the study 14. Presence of any of the following clinically significant laboratory abnormalities: (a) Haematocrit 3×the age-specific upper limit of normal (ULN), or total bilirubin >2×ULN (except known Gilbert’s disease). 15. Creatinine clearance =50 mL/min/1.73 m2 calculated using the child’s measured height (length) and serum creatinine within the updated “bedside” Schwartz formula (Schwartz et al, 2009): CrCl (mL/min/1.73m2)=0.413×height (length) (cm)/serum creatinine (mg/dL) 16. Patient has: (a) Evidence of immunocompromising condition (b) Concomitant medications that could interfere with the evaluation of antibacterial drug efficacy (e.g., immunosuppressant therapy) (c) Requirement for high-dose (eg, =2 mg/kg/day or a maximum of 20 mg/day of prednisone or equivalent) or prolonged systemic corticosteroid therapy. (Short courses of corticosteroids, such as those for currently worsening asthma, are permitted.) 17. History of seizures, excluding well-documented febrile seizure of childhood 18. Any situatio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Evaluate the descriptive efficacy of CAZ AVI plus metronidazole versus meropenem in paediatric patients aged =3 months to <18 years with cIAI Evaluate the PK of CAZ AVI in paediatric patients aged =3 months to <18 years with cIAI;Primary end point(s): To assess the safety and tolerability by : a) adverse events (AEs) and serious adverse events(SAEs) b) vital signs (pulse , blood pressure , respiratory rate, temperature) c) ECG (electrocardiogram) d) laboratory tests(complete blood count with differential and comprehensive metabolic panel ) e) creatinine clearance (CrCl);Timepoint(s) of evaluation of this end point: a) from ICF to LFU visit (27 to 50 days after start of study treatment) b)from ICF to LFU visit (27 to 50 days after start of study treatment) c) baseline, Day 1, TOC d)baseline , Days 4 to 15, EoIV (end of intravenous treatment) and TOC (test of cure) e)baseline;Main Objective: Evaluate the safety and tolerability of CAZ AVI plus metronidazole given at the selected dose regimen versus meropenem in paediatric patients aged =3 months to <18 years with cIAI | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.To assess the efficacy by: a) clinical outcomes b)microbiological response c)clinical relapse d) emergent infections 2. To evaluate the PK of CAZ-AVI in pediatric patients aged aged =3 months to <18 years with cIAI ;Timepoint(s) of evaluation of this end point: 1 a)end of 72 hours' treatment, end of intravenous treatment (EOIV), end of treatment (EOT) and test of cure (TOC) b) EOIV, EOT, TOC and LFU c)LFU d)study duration 2. Days 2 and 3 | — |
Countries
Argentina, Chile, Czech Republic, Greece, Hungary, Poland, Romania, Russian Federation, Spain, Taiwan, Turkey, United States
Contacts
Public ContactInformation Centre
AstraZeneca
Outcome results
None listed