Clinical trial NCT00921024: Safety and Efficacy of IV CXA-101 and IV Ceftazidime in Patients With Complicated Urinary Tract Infections
Official title: A Multicenter, Double-blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA-101 and Intravenous Ceftazidime in Complicated Urinary Tract Infection, Including Pyelonephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Complicated Urinary Tract Infection
Keywords: Complicated Urinary Tract Infection
Pyelonephritis
Antimicrobial
Cephalosporin
Intravenous
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2009-06-16
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of intravenous CXA 101 and comparator in complicated urinary tract infection

Detailed description: This is a Phase 2, multicenter, prospective, randomized, double-blind, comparative efficacy and safety study of IV CXA 101 versus IV ceftazidime for 7 to 10 days.

Subjects are followed up 6 to 9 days after the last dose of study drug to assess clinical signs and symptoms of infection. A Late Follow Up evaluation (21 to 28 days after the last dose of study drug) occurs for those subjects who respond to therapy. The primary assessment of effectiveness is the microbiological response (the eradication at post-therapy of the infectious organism identified at the start of study). An additional assessment of efficacy includes the overall clinical response, which is described as cured, improved, or failed. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, and urinalysis) and physical examinations at the start of the study and post-therapy.

Eligibility criteria: Inclusion Criteria:

1. Males and females 18 to 90 years of age, inclusive.
2. Pyuria (white blood cell \[WBC\] count \> 10/µL in unspun urine or ≥ 10 per high power field in spun urine)
3. Clinical signs and/or symptoms of cUTI, either of:

   a. Pyelonephritis, as indicated by both of the following: i. Fever (oral temperature ≥ 37.8°C); ii. Flank pain or costovertebral angle tenderness;

OR

b. Complicated lower UTI, as indicated by both of the following: i. At least one of the following new or worsening symptoms:

* Dysuria;
* Frequency;
* Suprapubic pain;
* Urgency

ii. At least one of the following complicating factors:

* Male gender;
* Current bladder instrumentation or indwelling urinary catheter that is expected to be removed during the course of IV study drug administration;
* Obstructive uropathy that is expected to be medically or surgically treated during the course of IV study drug administration;
* Urogenital surgery within 7 days preceding administration of the first dose of study drug;
* Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder with voiding disturbance of at least 100 mL residual urine.

Exclusion Criteria

1. Documented history of any hypersensitivity or allergic reaction to any β-lactam antibacterial
2. Concomitant infection requiring systemic antibacterial therapy in addition to IV study drug therapy at the time of randomization. Drugs with only gram-positive activity (e.g. vancomycin, linezolid) are allowed
3. Complete, permanent obstruction of the urinary tract
4. Confirmed (at time of randomization) fungal urinary tract infection (with ≥ 103 fungal CFU/mL)
5. Suspected or confirmed perinephric or intrarenal abscess
6. Suspected or confirmed prostatitis
7. Known ileal loop or vesico-ureteral reflux
8. Women who are pregnant or nursing

Primary outcomes:
measure: Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population
timeFrame: TOC; 6-9 days after last study drug administration
measure: Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.
timeFrame: TOC; 6-9 days after last study drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Healthcare Partners Medical Group
state: California
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Decatur
country: United States
facility: Atlanta Institute for Medical Research, Inc.
state: Georgia
city: Indianapolis
country: United States
facility: Infectious Disease of Indiana, PSC
state: Indiana
city: Picayune
country: United States
facility: Mississippi Medical Research, LLC
state: Mississippi
city: Butte
country: United States
facility: Great Falls Clinic, LLP
state: Montana
city: Columbus
country: United States
facility: Remington-Davis, Inc. Clinical Research
state: Ohio
city: Backnang
country: Germany
facility: Kreiskrankenhaus Backnang
city: Berlin
country: Germany
facility: URO Forschungs GmbH
city: Giessen
country: Germany
facility: Uniklinikum Giessen
city: Giessen
country: Germany
facility: Evangelisches Krankenhaus Giessen Urologie
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig Holstein Campus Lübeck
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef Paderborn
city: Planegg
country: Germany
facility: Urologische Klinik Dr. Castringius München-Planegg
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 Katedra i Klinika Nefrologii
city: Tychy
country: Poland
facility: Wojewódźki Szpital Specjalistyczny nr 1 Oddział Chorób Wewnętrznych
city: Warszawa
country: Poland
facility: Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych
city: Warszawa
country: Poland
facility: Szpital Kliniczny Dzieciątka Jezus-Centrum Leczenia Obrażeń Klinika Urologii Ogólnej, Onkologicznej Czynnościowej
city: Warszawa
country: Poland
facility: Szpital Praski p.w. Przemienienia Pańskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej ll Oddział Wewnętrznych
city: Wrocław
country: Poland
facility: Wojewódźki Szpital Specjalistyczny Oddział Nefrologiczny
city: Zamość
country: Poland
facility: Samodzielny Publiczny Szpital Wojewódźki im. Papieża Jana Pawła ll Oddział Wewnętrznych Nefrologiczno-Endokrynologiczny ze Stacją Dializ
Study officials:
affiliation: Mississippi Medical Research, LLC
name: Ahmad Haidar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych i Pododdział Nefrologiczny
name: Ryszard Gellert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uniklinikum Giessen
name: Florian Wagenlehner, MD
role: PRINCIPAL_INVESTIGATOR
References: