A Phase 3, Multicenter, Randomized, Double-Blind, Comparative Study to Evaluate the Safety and Efficacy of Ceftaroline Versus Vancomycin plus Aztreonam in Adult Subjects with Complicated Skin and Skin Structure Infectio
- Conditions
- Complicated Skin and Skin Structure Infections (cSSSI)MedDRA version: 8.1Level: LLTClassification code 10052891Term: Skin bacterial infection
- Registration Number
- EUCTR2006-005283-47-DE
- Lead Sponsor
- Cerexa, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 580
1.Age greater than or equal to 18 years
2.Skin and skin structure infection (SSSI) that meets EITHER of the following criteria:
• Involves deeper soft tissue or requires significant surgical intervention, such as a wound infection (surgical or traumatic), a major abscess, an infected ulcer, or deep and extensive cellulitis
o Deeper soft tissue” is defined as subdermal tissue, including subcutaneous fat; for
example, extension of infection to muscle or fascia constitutes evidence of deeper soft tissue involvement.
o Significant surgical intervention” is defined as a major operative procedure, not including commonly performed minor procedures such as incision and drainage of minor abscesses performed at the bedside, suture removal, needle aspiration, superficial debridement of devitalized tissue, or routine wound care.
o Wound infection” is defined by the presence of either purulent /seropurulent discharge from the surgical/traumatic wound or greater than or equal to 5 cm of erythema (i.e. cellulitis) surrounding the wound margin.1 Onset must have occurred within 7 days prior to randomization and no later than 30 days following the trauma or surgical procedure.
o Abscess” is defined by the presence of a loculated fluid collection with greater than or equal to 2 cm of erythema (i.e. cellulitis) extending from the abscess margin and onset within 7 days prior to randomization. A major abscess” either extends to deeper soft tissue or requires significant surgical intervention.
o Cellulitis” is defined by the presence of advancing erythema, edema and heat1 with onset within 7 days prior to randomization. Deep and extensive cellulitis” involves deeper soft tissue and has a surface area of greater than or equal to 10 cm2.
Or
• Cellulitis or abscess on a lower extremity which occurs in subjects with diabetes mellitus or well-documented peripheral vascular disease (PVD).
NOTE: Subjects with a history of diabetes mellitus must be taking insulin, insulin analogues, or oral hypoglycemic agents to be eligible for the study. Well-documented PVD” is defined as arterial or venous vascular disease resulting in ischemia of the lower extremity as manifest by ulceration, poor wound healing, or the absence of readily palpable dorsalis pedis and posterior tibial pulses. 2, 3 For purposes of this study, PVD does not include microvascular or lymphatic
drainage abnormalities.
3.Three or more of the following clinical signs:
·Purulent or seropurulent drainage or discharge
·Erythema
·Fluctuance
·Heat or localized warmth
·Pain or tenderness to palpation
·Fever greater than 38ºC oral (> 38.5ºC rectally or tympanically) or hypothermia (< 35ºC)
·White Blood Cell (WBC) count greater than 10,000/mm3
·Greater than 10% immature neutrophils (bands) irrespective of WBC count
4.The subject must require initial hospitalization, or treatment in an emergency room or urgent care setting, by the standard of care. Exception: subjects suitable for outpatient antimicrobial therapy (OPAT) may be enrolled with approval of the Medical Monitor
5.The subject’s infection is expected to require at least 5 days of IV antibiotic therapy.
6.Female subjects of child-bearing potential who are less than 2 years post-menopausal must agree to and comply with using highly effective methods of birth control ( e.g., condom +/- spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while par
1. History of any hypersensitivity or allergic reaction to any ß-lactam antibiotic
2.History of any hypersensitivity or allergic reaction to vancomycin or aztreonam
3.Past or current history of epilepsy or seizure disorder, excluding well-documented febrile seizure of childhood
4.More than 24 hours of treatment with a non-study antimicrobial (other than topical antibiotics) for the treatment of current cSSSI within 96 hours prior to randomization. EXCEPTION: Subjects may be eligible if they meet BOTH of the following conditions:
·Clinical evidence of failure following at least 48 hours of prior systemic antibiotic therapy
AND
·Microbiological evidence of failure
5.Failure of vancomycin or aztreonam as therapy for cSSSI, or prior isolation of an organism with in vitro resistance to vancomycin or aztreonam
6.Uncomplicated SSSI such as simple abscess, impetiginous lesions, superficial cellulitis, furunculosis, carbunculosis, or folliculitis. Skin and skin structure infections with a high cure rate after surgical incision alone or after aggressive local skin care (e.g., surgical site infection with a margin of less than 5 cm of surrounding cellulitis).
7.Skin and skin structure infection with ANY of the following characteristics:·-Known or suspected anaerobic pathogens (e.g., perirectal abscess)·
-Known or suspected fungal, parasitic, or viral pathogens·
-Known or suspected Pseudomonas aeruginosa as a contributing pathogen·
-Involving a decubitus ulcer·
-Involving a diabetic foot ulcer or an ulcer associated with PVD that has the following characteristics:
oAccompanied with osteomyelitis
oLikely to require amputation within 60 days
oLikely to require revascularization within 60 days
-Requiring significant surgical intervention that cannot be performed within 48 hours after initiating study drug therapy.
-Cases of cellulitis with a surface area less than 10 cm2 or a history consistent with clinical improvement or stabilization.
-Involving a third-degree burn or a burn covering more than 5% of total body surface area·Involving an underlying inflammatory skin disease that may obscure determination of response
-Involving human or animal bites (infections associated with arthropod bites may be allowed)
-Involving a rapidly necrotizing process, such as necrotizing fasciitis·
-Involving gangrene of any etiology
-Complicated by the presence of prosthetic materials that will not be removed, such as central venous catheters, permanent cardiac pacemaker battery packs, or joint replacement prostheses
-Likely to require amputation
8.Known or suspected endocarditis, osteomyelitis, or septic arthritis
9.Requirement for concomitant antibacterial or systemic antifungal therapy for any reason EXCEPTIONS: topical antiseptics (e.g., povidone-iodine [Betadine™], chlorhexidine [Hibiclens™], and alcohol and soaps for wound care), topical antifungal therapy, or a single oral dose of any antifungal for treatment of vaginal candidiasis are allowed.
10.Probenecid administration within 3 days prior to initiation of study drug or requirement for concomitant probenecid administration
11.Infections or conditions requiring concomitant systemic corticosteroid therapy at a dose equivalent to or greater than prednisone 40 mg per day
12.Severely impaired renal function (CrCl < 30 mL/min) estimated by the Cockroft-Gault formula
13.Evidence of significant hepa
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