Complicated urinary tract infections MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 100000005053
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Must be =3 calendar months to <18 years of age. Patients aged =3 calendar months to <1 year must have been born at term (defined as gestational age =37 weeks). 2.Written informed consent from parent(s) or other legally acceptable representative(s), and informed assent from patient (if age appropriate according to local regulations) 3.If female and has reached menarche, or has reached Tanner stage 3 development (even if not having reached menarche) (refer to Appendix E for further details on Tanner staging), the patient is authorised to participate in this clinical study if the following criteria are met: At screening: (i)(a) Patient reports sexual abstinence for the prior 3 months or reports use of at least one of the acceptable methods of contraception, including an intrauterine device (with copper banded coil), levonorgestrel intrauterine system (eg, Mirena®), or regular medroxyprogesterone injections (Depo-Provera®); or (b) Patient agrees to initiate sexual abstinence from the time of screening until 7 days after end of treatment with study drug; and (ii)Patient is advised to avoid conception from the time of screening until 7 days after receipt of study drug and agrees not to attempt pregnancy from the time of screening until 7 days after end of treatment with study drug; and (iii)Patient is provided guidelines regarding continuation of abstinence, initiation of abstinence, or about allowed contraception; and (iv)Patient has a negative serum ß-human chorionic gonadotropin (ß-hCG) test just prior to study entry. Since serum tests may miss an early pregnancy, relevant menstrual history and sexual history, including methods of contraception, should be considered. Note: if the result of the serum ß-hCG test cannot be obtained prior to dosing of investigational product, a patient may be enrolled on the basis of a negative urine pregnancy test, though a serum ß-hCG test result must still be obtained. 4.Patient has a clinically suspected and/or bacteriologically documented cUTI or acute pyelonephritis judged by the Investigator to be serious and requires the patient to be hospitalised for treatment with IV therapy 5.Patient has pyuria: ?Cohorts 1 to 3 as determined by a midstream clean catch or clean urethral catheterisation urine specimen with =10 white blood cells (WBCs) per high power field on standard examination of urine sediment or =10 WBCs/mm3 in unspun urine ?Cohort 4a and 4b as determined by a midstream clean catch or clean urethral catheterisation urine specimen or urine specimen obtained using urine collection pads (or supra-pubic collection if standard procedure in the assigned sites) =5 WBCs per high-power field on standard examination of urine sediment or =5 WBCs/mm3 in unspun urine 6.Patient has a positive urine culture: 1 midstream clean catch or clean urethral catheterisation urine specimen taken within 48 hours of randomisation containing =105 Colony-forming units (CFU)/mL of a recognised uropathogen known to be susceptible to the IV study therapy (CAZ-AVI and cefepime) 7.Demonstrates either acute pyelonephritis or complicated lower UTI as defined by the following criteria: (a)Qualifying criteria: patients must have at least 11 of the following signs/symptoms (signs/symptoms must have onset or have worsened within 7 days of enrolment) in addition to pyuria: ?Dysuria(including perceived dysuria as referred by parent/caregiver) ?Urgency ?Frequency ?Abdominal Pain Fever defined as oral
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, penicillins or other ß-lactam antibiotics 5. Concurrent infection, including, but not limited to, central nervous system infection requiring systemic antibiotics in addition to the IV study drug therapy at the time of randomisation 6. Receipt of more than 24 hours of any systemic antibiotics after culture and before study drug therapy 7. Receipt of systemic antibiotics within 24 hours before obtaining the study qualifying pre-treatment baseline urine sample and before study drug therapy 8. The child is suspected or documented to have an infection caused by organisms resistant to the prophylactic antibiotics 9. A permanent indwelling bladder catheter or instrumentation including nephrostomy or current urinary catheter that will not be removed or anticipation of urinary catheter placement that will not be removed during the course of IV study drug therapy administration 10. Patient has suspected or known complete obstruction of any portion of the urinary tract, perinephric abscess, or ileal loops 11. Patient has had trauma to the pelvis or urinary tract 12. Patient has undergone renal transplantation 13. Patient has a condition or history of any illness that, in the opinion of the Investigator, would make the patient unsuitable for the study (eg, may confound the results of the study or pose additional risk in administering the study therapy to the patient) 14. Patient is considered unlikely to survive the 6 to 8 week study period or have a rapidly progressive illness, including septic shock that is associated with a high risk of mortality 15. At the time of randomisation, patient is known to have a cUTI caused by pathogens resistant to the antimicrobials planned to be used in the study 16. 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) For a) to d): unless if these values are acute and directly related to the infectious process being treated. 17. Creatinine clearance<30 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) 18. History of seizures, excluding well-documented febrile seizure of childhood 19. If female, currently pregnant or breast feeding 20.Patient has: (a)Evidence of immunocompromising condition (b)Concomitant medications that could interfere with the evaluation of antibacterial drug efficacy (eg, 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 fo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety and tolerability of CAZ AVI given at the selected dose regimen versus cefepime in paediatric patients aged =3 months to <18 years with cUTI;Secondary Objective: 1.Evaluate the descriptive efficacy of CAZ-AVI versus cefepime in paediatric patients aged =3 months to <18 years with cUTI 2.Evaluate the PK of CAZ-AVI in paediatric patients aged =3 months to <18 years with cUTI;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); if clinically indicated (Days 2 and 3, EoT and LFU) e)baseline, Days 4 to 15, EoIV (end of intravenous treatment) and TOC (test of cure); if clinically indicated (Days 2 and 3, EoT and LFU) | — |
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
Czech Republic, Greece, Hungary, Korea, Republic of, Poland, Romania, Russian Federation, Taiwan, Turkey, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed