| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Complicated skin and skin structure infections | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | LLT | | E.1.2 | Level | code | | E.1.2 | Classification code | 10024768 | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To compare the clinical outcome following treatment with ceftobiprole or vancomycin of patients with cSSSI due to suspected or proven MRSS infection. | |
| E.2.2 | Secondary objectives of the trial | -To compare the microbiological outcome following treatment with ceftobiprole or vancomycinof patients with cSSSI due to suspected or proven MRSS infection.
-To compare the evaluation of signs and symptoms of cSSSI infections following treatment with ceftobiprole or vancomycin.
-To characterize the safety and tolerability of treatment with ceftobiprole. | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | 1)Written informed consent provided.
2)Male or female patients aged ≥ 18 years.
3)Patients who, in the opinion of the investigator, require antibiotic therapy with anti-MRSA antibiotic activity.
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:ofever (> 38°C rectal or > 37.5°C oral or > 38.5°C tympanic in the absence of anti-pyretics),
olocalized swelling,
olocalized erythema extending ≥10mm beyond wound edge,
olocalized pain,
otenderness to palpation
b)Onset of an abscess (without open wound) in the 7 days before enrollment with purulent drainage or purulent aspirate and evidence of loculated fluid that requires intervention within 48 hours of enrollment, and with 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:
ofever (> 38°C rectal or > 37.5°C oral or > 38.5°C tympanic in the absence of anti-pyretics) or reported fever in the 3 days before enrollment.
owhite blood cell (WBC) count ≥10 x 109/L, or ≥10% bands, or association with lymphangitis and adenopathy.
5)Suspected or proven infection with Gram-positive pathogen(s) with biological fluid/tissue samples available from infected lesion at baseline for microbiological culture.
6)Complications of infection comprising either a requirement for surgical intervention within 48 hours of enrollment, or involvement of subcutaneous tissues.
7)Severity of infection requiring hospitalization or prolongation of hospitalization.
8)Anticipated survival > 1 month. | |
| E.4 | Principal exclusion criteria | General:
1) Female patient who are pregnant or lactating.
2) Women of childbearing potential unable or unwilling to use an effective method of birth control.
3) Known or suspected hypersensitivity to any study medication (including β-lactam antibiotics such as penicillins or cephalosporins or vancomycin)
4) Any known or suspected condition or concurrent treatment contraindicated by the prescribing information for vancomycin.
5) Known or suspected severe renal impairment (calculated CrCl < 30 mL/minute, or oliguria < 20 mL/h unresponsive to fluid challenge) or any form of dialysis.See vancomycin prescribing information in Appendix 4 for dose adjustment in case of reduced CrCl.
6) Known or suspected hepatic dysfunction (total bilirubin, or alanine aminotransferase [ALT], or aspartate aminotransferase [AST] ≥ 3 x upper limit of the normal range [ULN])
7) Previous enrollment in this study
8) Treatment with any investigational drug within 30 days before enrollment
9) Any other known or suspected condition of the patient that may jeopardize adherence to protocol requirements.
Clinical conditions that may interfere with assessments of efficacy
10) 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 (sternotomy allowed, if infection is unlikely to extend into the mediastinum)
d) septic arthritis
e) toxic shock syndrome or shock.
11) Inability to start required interventions within 48 hours of enrollment (such as drainage or aspiration, suture removal, first debridement of tissue)
12) Super-infected eczema or neoplasia, decubitus ulcers, ischemic wounds where vascular supply is insufficient to allow wound healing
13) Neutropenic patients (absolute neutrophil count [ANC] ≤ 0.5 x 109/L) or patients with CD4 counts ≤0.2 x 109/L.
Microbiological conditions that may interfere with assessment of efficacy:
14) Systemic antimicrobial therapy > 24 hours in the 7 days before enrollment. 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 patient is clinically worsening despite at least 72 hours of treatment
15) Presence prior to study start of a pathogen known (or expected) to be resistant to either study drug
16) Suspected mixed infections that require treatment with medication other than the approved study medication
17) Self-limited infections such as isolated folliculitis or furuncules, furunculosis or carbunculosis not associated with cellulitis, or other infection that have a high cure rate after surgery alone.
18) Infections presumed at enrollment to be caused by Gram-negative pathogen(s) or mixed anaerobic/aerobic infections, such as:
a) decubitus ulcers, episiotomy infection, peri-anal cellulitis, Fournier’s gangrene
b) diabetic foot infections
c) infections due to animal or human bites
d) wound infections after surgical procedures where there is a high probability of Gram-negative pathogen(s), e.g,, if the infection extends to the oropharyngeal, gastrointestinal, urogenital or gynecological tract. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
