A randomized study in hospitalised patients with complicated urinary tract infections caused by Gram-negative bacteria to compare the efficacy and safety of S-649266 to Imipenem/Cilastin, both administered by intravenous infusio

Phase 1

• Conditions: Complicated Urinary Tract Infections with or without Pyelonephritis or Acute Uncomplicated Pyelonephritis caused by Gram-negative Pathogens; MedDRA version: 18.1Level: HLTClassification code 10046577Term: Urinary tract infectionsSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2014-000914-76-LV
• Lead Sponsor: Shionogi Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-11
• Last Update Posted: 26 September 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Hospitalized patients who have a clinical diagnosis of either cUTI with or without pyelonephritis or acute uncomplicated pyelonephritis, and who have provided written informed consent or informed consent provided by legal guardian. (Note: Country specific rules and local Ethics Committee approval for legal guardian informed consent will determine whether or not a patient unable to comprehend or sign the informed consent is allowed to be enrolled in the study).
The specific clinical diagnosis will include:

cUTI with a history of at least one of the following:
•Indwelling urinary catheter or recent instrumentation of the urinary tract (within 14 days prior to screening)
•Urinary retention caused by benign prostatic hypertrophy
• Urine retention of at least 100 millileters (mL) or more of residual urine after voiding (neurogenic bladder)
•Obstructive uropathy (nephrolithiasis, fibrosis, etc.)
•Azotemia caused by intrinsic renal disease (BUN and creatinine values greater than normal laboratory values)
OR
Pyelonephritis and normal urinary tract anatomy, ie, acute uncomplicated pyelonephritis

AND
All patients must have at least two of the following signs or symptoms:
•Chills or rigors or warmth associated with fever (temperature greater than or equal to 38 degrees Celsius)
•Flank pain (pyelonephritis) or suprapubic/pelvic pain (cUTI)
•Nausea or vomiting
•Dysuria, urinary frequency, or urinary urgency
•Costo-vertebral angle tenderness on physical examination

AND
Urinalysis evidence of pyuria demonstrated by:
•Dipstick analysis positive for leukocyte esterase
•Or =10 WBCs per µL in unspun urine, or =10 WBCs per high power field in spun urine)
2. Patients who had a positive urine culture obtained within 48 hours prior to randomization containing = 100000CFU/mL of a Gram-negative uropathogen likely to be susceptible to imipenem are eligible for this study (Note: patients may be enrolled prior to the results of the urine culture being available)
3. Patients, who have been treated previously with an empiric antibiotic other than the study medications, but failed treatment, both clinically and microbiologically, are eligible for the study if they have an identified uropathogen which is non-susceptible to the empiric treatment and is a Gram-negative uropathogen likely to be susceptible to imipenem (or alternative carbapenem antibiotic).
4. Female patients can participate if they are surgically sterile or have completed menopause, or if they are capable of having children, are not pregnant or nursing and they agree not to attempt pregnancy from the screening until end of study (EOS) (approximately 28 days following EOT) or according to country specific requirements, whichever is longer.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 220

Exclusion Criteria

1. Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other ß-lactam antibiotics
2. Patient's urine culture at study entry isolates more than 2 uropathogens, regardless of colony count, or patient has a confirmed fungal UTI.
3. Patients with asymptomatic bacteriuria, the presence of =100000CFU/mL of a uropathogen and pyuria but without local or systemic symptoms
4. Patient is receiving hemodialysis or peritoneal dialysis. Impairment of renal function with an estimated CrCl < 21 mL/min, requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified