An open label, multi-center, randomized, comparative Phase IIIb study to compare efficacy and safety of intravenous (i.v.) daptomycin with that of Semi-synthetic Penicillins (SSPs) or vancomycin in the treatment of elderly patients (aged ≥ 65 years) with complicated Skin and Soft Tissue Infections (cSSTIs) - ND

Conditions: Complicated skin and soft tissue infections

Registration Number: EUCTR2009-014391-22-IT

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 146

Inclusion Criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Written informed consent to participate in the study. In the event that the patient is unable to give consent, the patient`s legally authorized representative may do so by means approved by the investigator s EC. 2. Patients with age of 65 years or older. 3. Infection of sufficient severity to require in-patient hospitalization, with parenteral antimicrobial therapy for at least 96 hours. 4. Patients who have a diagnosis of Gram-positive complicated skin and soft tissue infections (cSSTIs) with or without bacteremia, e.g.: wound infections due to: o traumatic injury (e.g., crush, puncture, laceration, gunshot, etc.), o surgical incision, o foreign body (e.g., septic phlebitis associated with intravenous catheter sites). Infected foreign bodies (e.g., implanted pacemakers) are to be removed within 24 hours following study enrolment. major abscesses which are defined as meeting all the following criteria: o involve the subcutaneous or deeper tissues o require surgical incision and drainage, o require antibiotic therapy in addition to drainage. severe carbunculosis, infected ulcers (except patients with multiple infected ulcers, see exclusion criteria) associated with: diabetes, vascular insufficiency, pressure (i.e., decubitus ulcers), presence of a complicating factor, including: o a pre-existing skin lesion or underlying condition that adversely affected the delivery of drug to the affected area, the immunologic response, or tissue healing, o requirement for significant surgical intervention, o suspected or confirmed involvement of deep soft tissues, fascia, or muscle, o chronic systemic steroids (> 20 mg prednisone daily or equivalent), o diabetes mellitus requiring treatment with oral hypoglycemic agents or insulin. 5. Presence of at least 3 of the following signs and symptoms of skin infection: temperature > 38.0C rectal or > 37.5C oral/tympanic, elevated WBC >12x 103/μL or with > 10 % bands (immature neutrophils), drainage and/ or discharge from the infection site, erythema (extending at least 1 cm beyond wound edge), fluctuance, heat and/ or localized warmth, pain and/ or tenderness to palpation, edema and/ or induration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Non-complicated SSTI: 1.Conditions requiring surgery that in and of itself would cure the infection or remove the infected site (e.g., amputation). 2.Minor or superficial skin infections (e.g., furuncles, simple abscesses, acne, impetigo). 3.Cellulitis, including erysipelas, not associated with complicating factors. However, patients with cellulitis associated with more serious infection (e.g., surgical wound, diabetic ulcer, deep tissue) can be enrolled (proportion of these patients will be limited to 30%). Infections for which outcome is difficult to assess: 4.Perirectal abscess 5.Hidradenitis suppurativa 6.Gangrene 7.Infected human or animal bites 8.Multiple infected ulcers at distant sites 9.Infected burns (only 3rd degree burn wound or wound area of more than 10 cm diameter) 10.Conditions requiring emergency surgery including necrotizing fasciitis. Medical conditions: 11.History of significant allergy or intolerance to vancomycin or daptomycin. Hypersensitivity to the selected SSPs is not an exclusion criterion. 12.Concomitant clinically suspected or confirmed other site of infection or disorder at study entry that may interfere with the evaluation in this protocol such as primary muscle disorders, pneumonia, endocarditis, osteomyelitis, septic arthritis, meningitis, spinal epidural abscess, intraabdominal infection (peritonitis, etc.) and intravascular devicerelated bacteremia. 13.Infections associated with a permanent prosthetic device that will not be removed within 24 hours after enrolment. 14.Shock or hypotension (supine systolic blood pressure < 80 mm Hg) refractory to fluid or short course pressor challenge (> 4 hours). 15.Neutrophil count < 1000/μL. 16.Known or suspected HIV infection with a CD4+ T-cell count < 500/μL (HIV testing is not required). 17.Severe hepatic disease (Child-Pugh Class C) or ALT and/or AST > 5 times ULN and/ or total bilirubin > 2 times ULN at screening. 18.Calculated creatinine clearance by the Cockcroft-Gault equation using actual body weight < 30 mL/min or any type of dialysis. 19.Life expectancy less than six months. 20.Treatment with any investigational agent or device within 30 days of study drug administration. 21.Patients unwilling or unable to adhere to study-designated procedures and restrictions. 22.Patients admitted to the hospital for drug abuse or other conditions associated with rhabdomyolysis. Exclusion criteria related to microbiology 23.Patients with an infection due to an organism known to be resistant to daptomycin or vancomycin at study entry. 24.cSSTIs suspected or documented as being due exclusively to Gram-negative or anaerobic organisms based on the epidemiology or on direct examination of a Gram- stained specimen. Exclusion criteria related to medications 25.Need at study entry, for a non-study systemic antibacterial (for concomitant infection) to which the target pathogen is susceptible. 26.Previous systemic antibacterial therapy for the treatment of Gram-positive cSSTIs for more than 24 hours within 48 hours prior to the day of first infusion of study drug unless: the infecting Gram-positive pathogen is intermediate or resistant in vitro to the previous antibacterial therapy; or the previous antibacterial therapy was administered for 3 or more calendar days with either worsening or no improvement in the clinical signs and symptoms of cSSTI, and was not vancomycin or SSP.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate and descriptively compare clinical success at the Test-Of-Cure visit (TOC) in elderly patients (aged ≥ 65 years) with cSSTIs, treated with either 4 or 6 mg/kg once daily i.v. daptomycin and with comparator.;Secondary Objective: To descriptively evaluate the microbiological outcome of daptomycin in comparison to that of comparator in the treatment of cSSTIs as measured by the proportion of patients achieving bacteriological eradication of Grampositive baseline pathogens at the TOC visit. To evaluate the duration of treatment (i.v., i.v. + oral). To evaluate and descriptively compare adverse event frequencies and laboratory abnormalities in elderly patients treated with 4 and 6 mg/kg once daily of i.v. daptomycin and with comparator (Safety evaluation).;Primary end point(s): See primary objective section

Secondary Outcome Measures

Name	Time	Method

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