Hospitalized Adults With Complicated Urinary Tract Infections including infection reaching their kidneys will be treated with either cefepime in combination with AAI101 or cefepime alone. Neither the participants nor the research staff know the identity of the administered drug. cefepime/AAI101 or cefepime alone will be assigned using a method based on chance.
- Conditions
- Complicated urinary tract infections including acute pyelonephritisMedDRA version: 20.0Level: PTClassification code 10037597Term: Pyelonephritis acuteSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 20.0Level: HLTClassification code 10046577Term: Urinary tract infectionsSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2016-005161-31-PL
- Lead Sponsor
- Allecra Therapeutics SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 63
1. Males or females 18 to 90 years of age, inclusive, at the time of signing of informed consent;
2.Expectation that the patient’s cUTI or acute pyelonephritis would require hospitalization and initial treatment with at least 7 days of i.v. antibiotics;
3.Female patients can participate if at least 1 of the following criteria are met:
- Surgical sterilization;
- Age > =50 years and post-menopausal as defined by amenorrhea for > = 12 months following cessation of all exogenous hormonal treatments;
- Age < 50 years and post-menopausal as defined by documented luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range PLUS amenorrhea for > = 12 months following cessation of all exogenous hormonal treatments; or
- Patient has a negative urine and/or serum pregnancy test (serum ß-human chorionic gonadotropin) within 1 day prior to study entry, and agrees to use highly effective contraception methods during treatment and for at least 7 days after the last dose of i.v. study therapy;
4. Male patients are required to practice reliable birth control methods (condom or other barrier device) during the conduct of the study and for at least 35 days after the last dose of study drug;
5. Pyuria, defined as:
- White blood cell count >10 cells/mm3 in unspun urine or > = 10 cells/high power field in spun urine sediment; or
- Urinalysis/dipstick analysis positive for leukocyte esterase;
6. Clinical signs and/or symptoms of cUTI or acute pyelonephritis as defined in the section 4.1 of the study protocol :
Acute Pyelonephritis:
At least 2 of the following new or worsening symptoms:
• Fever (oral/tympanic > =38°C [> = 100.4°F] or rectal/core temperature > =38.3°C [ > =100.9°F]) observed and documented by a health care provider within 24 h of the screening visit, accompanied by patient symptoms of rigors, chills, or warmth”;
• Flank pain (onset within 7 days prior to randomization);
• Dysuria, increased urinary frequency, or urinary urgency;
• Costovertebral angle tenderness or suprapubic tenderness on physical examination; or
• Nausea or vomiting within 24 h of the screening visit, as reported by the patient.
CUTI
At least 2 of the following new or worsening symptoms:
• Dysuria, increased urinary frequency, or urinary urgency;
• Fever (oral/tympanic > = 38°C [> =100.4°F] or rectal/core temperature > = 38.3°C [ > = 100.9°F]) must be observed and documented by a health care provider within 24 h of the screening visit, accompanied by patient symptoms of rigors, chills, or warmth”;
• Lower abdominal pain or pelvic pain;
• Costovertebral angle tenderness or suprapubic tenderness on physical examination; or
• Nausea or vomiting within 24 h of the screening visit as reported by the patient; AND
At least 1 of the following complicating factors:
• Male patients with documented history of urinary retention, for example, benign prostatic hypertrophy;
• Use of intermittent bladder catheterization or presence of an indwelling bladder catheter;
NOTE: Indwelling bladder catheters that have been in place for > 24 h prior to the screening visit must be removed or replaced prior to collection of the screening visit urine for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated.
• Current obstructive uropathy that is scheduled to be medically or surgically relieved during i.v. study therapy and before EOT;
• Any functional or anatomical abnormality of the urogeni
1. History of serious allergy, hypersensitivity (e.g. anaphylaxis), or any serious reaction to cefepime, any cephalosporin, penicillins, ß-lactamase inhibitors (e.g. tazobactam, sulbactam, or clavulanic acid), or other ß-lactam agents;
2. Concurrent infection that would interfere with evaluation of response to the study antibiotics;
3. Need for concomitant systemic antimicrobial agents in addition to those designated in the various study treatment groups;
4. Receipt of any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug;
5. Receipt of effective antibacterial drug therapy for cUTI for a continuous duration of >24 h during the previous 72 h before the study-qualifying baseline urine is obtained;
EXCEPTION: Patients who have 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 likely to be susceptible to the study drug; OR patients who received antibacterial drugs for surgical prophylaxis and then developed cUTI.
6. Complicated urinary tract infection known at study entry to be caused by pathogens resistant to the study antibiotics;
7. Intractable urinary infection at baseline that the Investigator anticipates would require >10 days of study drug therapy;
8. Complete, permanent obstruction of the urinary tract that is not anticipated to be medically or surgically relieved during i.v. study therapy and before End of Treatment;
9. Confirmed fungal urinary tract infection at the screening visit
10. Presence of any known or suspected disease condition that, in the opinion of the Investigator, may confound the assessment of efficacy, including but not limited to, the following:
Perinephric abscess;
Renal corticomedullary abscess;
Uncomplicated urinary tract infection;
Any recent history of trauma to the pelvis or urinary tract;
Polycystic kidney disease;
Chronic vesicoureteral reflux;
Previous or planned renal transplantation;
Previous or planned cystectomy or ileal loop surgery;
Patients receiving dialysis, including hemodialysis, peritoneal dialysis, or continuous veno-venous hemofiltration; or
Known or suspected infection that is caused by pathogen(s) resistant to either study drug, including infection caused by fungi (e.g. candiduria) or mycobacteria (e.g. urogenital tuberculosis);
11. Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;
12. Estimated creatinine clearance <60 mL/min calculated by Cockcroft-Gault method
13. Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure and respiratory failure;
14. Any signs of severe sepsis, including but not limited to, the following:
Shock or profound hypotension, defined as systolic blood pressure <90 mmHg or a decrease of >40 mmHg from baseline, that is not responsive to fluid challenge; or
Disseminated intravascular coagulation as evidenced by prothrombin time or partial thromboplastin time >=2 × the upper limit of normal (ULN), or <50,000 platelets/mm3 at the screening visit in patients in whom severe sepsis is suspected;
15. A QT interval corrected using Fridericia’s formula >450 msec;
16. Immunocompromising condition including established acquired immune defici
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