A Phase 3, Randomized, Double-Blind Study Of Ceftobiprole Medocaril Versus Vancomycin With Ceftazidime in The Treatment Of Complicated Skin And Skin Structure Infections - STRAUSS

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-002301-23-HU
• Date of registration: 20/10/2005
• Prospective Registration: Yes
• Primary sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Public title: A Phase 3, Randomized, Double-Blind Study Of Ceftobiprole Medocaril Versus Vancomycin With Ceftazidime in The Treatment Of Complicated Skin And Skin Structure Infections - STRAUSS
• Scientific title: A Phase 3, Randomized, Double-Blind Study Of Ceftobiprole Medocaril Versus Vancomycin With Ceftazidime in The Treatment Of Complicated Skin And Skin Structure Infections - STRAUSS
• Date of first enrolment: 14/12/2005
• Target sample size: 816
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002301-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Czech Republic, Estonia, Hungary, Latvia, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
1) Written informed consent provided.
2) Male or female subjects aged =18 years.
3) Female subjects must be postmenopausal (for at least one year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections or patch, intrauterine device, double-barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], male partner sterilization or, at the discretion of the investigator, abstinence), before entry and throughout the study; have a negative serum or urine pregnancy test (depending on local regulations) at screening.
4) Diagnosis of an infection consistent with cSSSI (defined as infections either involving deeper soft tissue or requiring significant surgical intervention) and one or more of the following:
a) Infection site within 30 days of surgery/trauma (including partial thickness burns <10% body surface) with purulent drainage from the lesion OR AT LEAST THREE of the following signs:
? fever (>38°C rectal or >37.5°C oral or >38.5°C tympanic in the absence of antipyretics),
? localized swelling
? localized erythema extending = 10 mm beyond wound edge
? localized pain,
? tenderness to palpation
b) Abscess fulfilling ALL of the following criteria:
o onset =7 days before enrollment (without open wound)
o purulent drainage or purulent aspirate at the time of enrollment
o evidence of loculated fluid that requires incision and drainage within 48 hours of
enrollment
o erythema and/or induration of =20 mm diameter, or tenderness.
c) Onset of cellulitis in the 7 days before enrollment with advancing edema, erythema, or induration and ONE of the following:
o fever (>38°C rectal or >37.5°C oral or >38.5°C tympanic in the absence of antipyretics) or reported fever in the 3 days before enrollment.
o white blood cell (WBC) count =10 x 109/L, or =10% bands, or association with
lymphangitis and adenopathy.
d) Foot infections in diabetic subjects: infra-malleolar full skin thickness ulcer, cellulitis, myositis, or tendonitis with AT LEAST THREE out of the following:
o localized swelling
o localized erythema
o tenderness to palpation
o increased skin temperature
5) Complications of infection comprising either a requirement for surgical intervention within 48 hours of enrollment, or involvement of subcutaneous tissues. (Diabetic subjects could have undergone any necessary debridement or other surgical procedures, as long as the entire infected area was not resected or amputated).
6) Infection with Gram-positive or Gram-negative pathogen(s) or mixed infections with biological fluid/tissue samples available from infected lesion at baseline for microbiological culture.
7) Severity of infection requiring hospitalization or continuation of hospitalization.
8) Anticipated survival >1 month.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
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:
General:
1) Female subjects who are pregnant or lactating.
2) Known or suspected hypersensitivity to any study medication or other related anti-infective medication (including ß-lactam antibiotics such as penicillins or cephalosporins or vancomycin).
3) Any known or suspected condition or concurrent treatment contraindicated by the prescribing information for vancomycin or ceftazidime.
4) Known or suspected severe renal impairment (calculated creatinine clearance [CrCl] <30 mL/minute, or oliguria <20 mL/h unresponsive to fluid challenge) or any form of dialysis.
5) Known or suspected hepatic dysfunction (total bilirubin = 2 x upper limit of the normal range [ULN], or alanine aminotransferase [ALT] =3 x ULN, or aspartate aminotransferase [AST] =3 x ULN).
6) QTcB (Bazett's correction) >450 msec at baseline
7) Previous enrollment in this study or any other ceftobiprole study.
8) Treatment with any investigational drug within 30 days before enrollment.
9) Any other known or suspected condition of the subject that may jeopardize adherence to protocol requirements.
10) Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

Clinical conditions that may interfere with assessments of efficacy:
11) Diagnosed or suspected:
a) Infection related to a foreign body (e.g., intravascular catheter or prosthetic material) that cannot be removed within 24 hours after enrollment,
b) endocarditis,
c) osteomyelitis (diagnosed by the presence of visible bone, an x-ray characteristic for osteomyelitis, and x-ray compatible with osteomyelitis or a high clinical suspicion
confirmed by MRI or bone biopsy. Sternotomy allowed, if infection is unlikely to
extend into the mediastinum). A subject with positive probe to bone finding is excluded unless a bone biopsy, MRI, or nuclear medicine scan has excluded osteomyelitis. Diabetic subjects with underlying osteomyelitis who
have had involved bone resected surgically within 7 days prior to randomization
should not be enrolled
d) septic arthritis,
e) toxic shock syndrome or shock,
f) necrotizing fasciitis,
g) gas gangrene.
12) Inability to start required interventions within 48 hours of enrollment (such as drainage or aspiration, suture removal, first debridement of tissue).
13) Superinfected eczema or neoplasia.
14) Potentially critical limb ischemia defined by one or more of the following criteria:
a) claudication <1 block walking,
b) absence of pedal pulses,
c) absent Doppler wave forms,
d) toe blood pressure of <30 mmHg, ankle blood pressure of <50 mmHg, TcpO2
<30,
15) Neutropenic subjects (absolute neutrophil count [ANC] =0.5 x 109/L) or HIV subjects with
CD4 counts =0.2 x 109/L.
Microbiological conditions that may interfere with assessment of efficacy:
16) Systemic antimicrobial therapy >24 hours in the 3 days before enrollment.
Exception: Systemic antimicrobial therapy for >24 hours is permitted in case:
a) The infection is caused by microbiologically-confirmed pathogens that are resistant
to the previous antimicrobial agents.
b) The subject is clinically worsening despite at least 72 hours of treatment and the
pathogens suspected or identified as causing the infection are susceptible to study
drug regimens.
17) Presence prior to study start of a pathogen known (or expected) to be resistant to either study drug.
18) Suspected mixed infecti

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

complicated skin and skin structure infection
MedDRA version: 5.1 Level: HLT Classification code 10040786

Intervention(s)

Product Name: Ceftobiprole
Product Code: BAL5788 (Laboratory Code)
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Ceftobiprole medocaril
CAS Number: 252188-71-9
Current Sponsor code: BAL5788
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Vancomycin
Product Name: Vancomycin
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Vancomycin
CAS Number: 1404-93-9
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Biotum
Product Name: Biotum
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Ceftazidime
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Ceftazidima EG
Product Name: Ceftazidima EG
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Ceftazidime
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Reconstitution solution for Ceftobiprole Medocaril.
Pharmaceutical Form:
Other descriptive name: 1%Anhydrus Glucose,0.84%Citrus Acid Monohydrate,Sodium Hydroxide q.s. to pH5.0(c.a.0,35%),water
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Vancomicina
Product Name: Vancomicina
Pharmaceutical Form:
INN or Proposed INN: Vancomycin
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: - To compare the microbiological eradication rate following treatment with ceftobiprole/placebo or vancomycin/ceftazidime of subjects with cSSSI at the test-of-cure (TOC) visit
- To compare the microbiological relapse rate and clinical cure rate following treatment with ceftobiprole/placebo or vancomycin/ceftazidime of subjects with cSSSI at the late follow-up (LFU) visit

Main Objective: To demonstrate the noninferiority of ceftobiprole/placebo compared with Vancomycin/ceftazidime with respect to clinical cure rate in subjects with complicated skin and skin structure infections (cSSSI) at the test-of-cure (TOC) visit

Primary end point(s): Clinical cure rate defined as the ratio of the number of clinically cured subjects to the total number of subjects in the population at test-of-cure (TOC) visit.

Secondary ID(s)

BAP00414