A clinical study in patients with complicated infections of the urinary tract conducted to assess safety, tolerability and efficacy of the study drug (MK-7655) administered together with Imipenem/Cilastatin (an antibiotic) in comparison with Imipenem/Cilastatin administered alone
- Conditions
- Patients with Complicated Urinary Tract Infection at least 18 years of age, with a diagnosis of either complicated cUTI or acute pyelonephritisMedDRA version: 17.1Level: LLTClassification code 10046544Term: Urinary infectionSystem Organ Class: 100000004862MedDRA version: 17.1Level: LLTClassification code 10001032Term: Acute pyelonephritisSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2011-005707-32-LV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
1. Patient is =18 years of age on day of signing informed consent.
2. Patient or the patient’s legal representative understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical
Research.
3. Sexually active females of childbearing potential with a negative urine pregnancy test are eligible for enrollment; however, this must be followed up with a confirmed
negative serum pregnancy test (ß-HCG) as soon as possible (within 48 hours of the screening visit).
A patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) a medically acceptable effective method of birth control until study
completion. To be considered abstinent, abstinence must be in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (e.g., abstinence only on certain
calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception]. Patients in regions in which abstinence is not a locally acceptable method of contraception must use another medically acceptable effective birth control method. Effective method of birth control is defined as a marketed, approved
contraceptive product that the patient has used per the manufacturer’s instructions with every act of sexual intercourse. The rhythm method alone, withdrawal alone, and
emergency contraception, are not medically acceptable methods per the protocol.
4. Patient has a clinically suspected and/or bacteriologically documented cUTI OR acute pyelonephritis judged by the investigator to be serious (requiring hospitalization and
treatment with IV antibiotic therapy) according to the following disease definitions:
a) Acute pyelonephritis is defined as a systemic, ascending urinary tract infection in a patient with normal urinary tract anatomy, clinically manifested by meeting at least 2 of the following criteria:
• Fever (defined as =38.0°C [=100.4°F] orally OR an oral equivalent [=38.5°C (=101.3°F) by tympanic or rectal measurement])
• Flank pain
• Costovertebral angle (CVA) tenderness on physical examination
• Nausea or vomiting
b) Complicated UTI (cUTI) is defined as a clinical syndrome in men or women characterized by the development of at least 2 of the following local or systemic signs and symptoms:
• Local signs and symptoms: Dysuria, urinary frequency, suprapubic or pelvic pain, or urinary urgency
• Systemic signs and symptoms: Fever (as defined above), chills or rigors (accompanied by fever), flank pain or CVA tenderness on physical examination The above symptoms must also occur in the presence of at least 1 of the following
conditions, which increase the risk of developing an infection:
• Presence of indwelling urinary catheter or other urinary bladder instrumentation
• Any functional or anatomical abnormality of the urogenital tract (including anatomic malformations or neurogenic bladder) with voiding disturbance resulting in at least 100 mL of residual urine
• Current obstructive uropathy (nephrolithiasis or fibrosis) that is scheduled to be medically or surgically relieved during IV study therapy
• Males with documen
1. Patient has complete obstruction of any portion of the urinary tract (requiring a permanent indwelling urinary catheter or instrumentation), has a known ileal loop, or
intractable vesico-uretral reflux.
2. Patient has a cUTI in whom a temporary indwelling urinary catheter is in place and cannot be removed at study entry
NOTE: All indwelling urinary catheters must be removed prior to the start of IV study therapy. Unless medically necessary, it is recommended that an indwelling urinary catheter not be reinserted during the study (at least while on IV study therapy).
3. Patient has a perinephric or intrarenal abscess or known or suspected prostatitis.
4. Patient has an uncomplicated UTI (e.g., a female patient with urinary frequency, urgency or pain/discomfort without any risk factors for infection as outlined in Inclusion Criteria #4b).
5. Patient has any history of recent accidental trauma to the pelvis or urinary tract.
6. Patient has received any amount of effective antibiotic therapy (defined as therapy known to be active against the identified uropathogen) after obtaining the urine culture for admission to this study (admission urine culture) and prior to the administration of the first dose of IV study therapy.
7. Patient has an infection which has been treated with >24 hours of systemic antibiotic therapy known to be effective against the presumed or documented etiologic pathogen(s) within the 72-hour period immediately prior to consideration for entry into the study (only patients with a urine culture positive for the presence of at least 1 gram-negative enteric(s) and/or anaerobic pathogen(s) commonly isolated in UTI will
be considered microbiologically evaluable).
8. Patient has a history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to carbapenem antibiotics, any cephalosporins, penicillins, or other ß-
lactam agents.
9. Patient has a history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to other ß- lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid).
10. Patient has a history of a seizure disorder.
11. Patient is currently being treated with valproic acid or has received treatment with valproic acid in the 2 weeks prior to screening.
12. Patient has a rapidly progressive or terminal illness (unlikely to survive the approximately 6- to 8-week study period).
13. Patient is pregnant or expecting to conceive, is breast feeding, or plans to breast feed during participation in the study.
14. Patient in whom a response to all study therapy (IV study therapy or subsequent oral ciprofloxacin) within the timeframe of treatment specified in this protocol is
considered unlikely.
15. Patient has a concurrent infection that would interfere with evaluation of response to the study antibiotics (imipenem/cilastatin with or without MK-7655).
16. Patient has a need for concomitant systemic antimicrobial agents in addition to those designated in the various study treatment groups.
17. Patient has a cUTI due to a confirmed fungal pathogen.
18. Patient is currently receiving immunosuppressive therapy, including use of high-dose corticosteroids (i.e., >40 mg prednisone or prednisone equivalent per day).
19. Patient is a prior recipient of a renal transplantation.
20. Patient has estimated or actual creatinine clearance of less than or equal to 5 mL/min, or is currently undergoing hemodialysis.
21. The patient has any of the following
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