| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Complicated skin and soft tissue infections (cSSTI) |
|
| MedDRA Classification |
| 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 efficacy of daptomycin to that of the comparator arm (vancomycin or teicoplanin) in the treatment of cSSTI as measured by the proportion of subjects achieving clinical success at the Test-of-Cure (TOC) visit (Day +7 to Day +14). |
|
| E.2.2 | Secondary objectives of the trial |
To compare the time to resolution of clinical signs and symptoms of cSSTI in the daptomycin arm with that of the comparator arm, according to a SSTI signs & symptoms scoring system.
To compare the time to resolution of fever in daptomycin-treated subjects with that in comparator-treated subjects.
To compare the microbiological efficacy of daptomycin with that of vancomycin or teicoplanin in the treatment of cSSTI as measured by the proportion of subjects achieving bacteriological eradication of Gram-positive baseline pathogens at the TOC visit.
To assess and compare the resource utilisation, treatment cost, and cost-effectiveness of daptomycin with the comparator treatment over the treatment and follow-up period.
To compare the duration of treatment with daptomycin with that of comparator.
To compare safety of treatment with daptomycin with that of comparator. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1.Subjects with a diagnosis of cSSTI defined as infection normally requiring surgical/local debridement of sufficient severity to warrant hospitalisation and i.v. antimicrobial treatment.
2.Infection known or suspected (based on Gram’s stain) to be due, at least partially, to Gram-positive bacteria.
3.Hospitalised subjects with clinical evidence of at least one of the following: Infected ulcers including diabetic foot ulcers not associated with osteomyelitis-
Major abscess-
Deep or extensive cellulitis -
Post-surgical / post-traumatic wound infection-
4.Presence of at least two of the following signs and symptoms:
Drainage and/or discharge from the infection site-
Erythema-
Edema and/or induration-
Heat and/or localised warmth-
Pain and/or tenderness to palpation-
Temperature >38.0°C rectal or >37.5°C oral/tympanic-
WBC >12 x 103 /L or with >10% bands
5.Written informed consent to participate in the study.
6.Males and females at least 18 years of age.
7.Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test at Baseline and the subject must agree to an effective method of contraception throughout the study period. |
|
| E.4 | Principal exclusion criteria |
1.cSSTIs of the following categories:-
Infected burns-
Severely impaired arterial blood supply such that the likelihood of amputation of the infected anatomical site is likely -
Decubitus ulcers -
Infected diabetic foot ulcers associated with osteomyelitis-
Infected human or animal bites-
Superficial infections or abscesses in an anatomic site, such as the rectal area, where the risk of anaerobic or Gram-negative pathogen involvement is high (e.g. perirectal abscess)-
Necrotising fasciitis or gangrene-
cSSTI expected to require more than 14 days of intravenous antimicrobial therapy -Skin and/or skin structure infection that can be treated by surgery alone-Infections associated with a permanent prosthetic device that will not be removed within 2 days of study randomisation
2.Uncomplicated skin or soft tissue infection (e.g., simple abscesses, folliculitis, impetiginous lesions, furunculosis, superficial cellulitis).
3.Subjects with documented bacteraemia at Baseline.
4.Shock or hypotension (supine systolic blood pressure <80 mmHg) refractory to fluid or short course pressor challenge (four hours or less).
5.Concomitant clinically suspected or confirmed other site of infection or disorder at study entry that may interfere with the evaluations in this protocol (e.g. primary muscle disorders, endocarditis)
6.Treatment with vancomycin or teicoplanin within the past 48 hours, unless administered for less than 24 hours.
7.Subjects admitted to the hospital for conditions associated with rhabdomyolysis.
8.Subjects with an infection due to an organism known prior to study entry to be resistant to daptomycin, vancomycin or teicoplanin.
9.Previously diagnosed disease of immune function (e.g. AIDS, neutrophil count <1000mm/m3).
10.Subjects receiving oral steroids >10 mg per day prednisolone or equivalent or receiving immunosuppressant drugs after organ transplant.
11.Complicated SSTI that is known or suspected to be a fungal, parasitic or viral infection.
12.Subjects diagnosed with pneumonia.
13.Pregnant or lactating women.
14.Severe renal impairment with creatinine clearance (CrCl) <30 mL/min or dialysis.
15.Severe hepatic disease (Child-Pugh Class C) or known ALT and/or AST >3 times the upper limit of normal and/or bilirubin >1.5 times the upper limit of normal. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable related to the primary objective of the study is the Clinical Success (i.e. clinical cure or clinical improvement) at the Test of Cure (TOC) visit in the Clinically Evaluable (CE) study population.
At the time of TOC assessment, clinical response will be determined in the CE population by comparing the subject's signs and symptoms to those recorded at Study Baseline and classified into the following categories as described in the protocol:
Success
Failure
Unable to evaluate |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| 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) | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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 | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
|
| Last visit of 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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