E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated skin and soft tissue infections |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10049582 |
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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 linezolid to vancomycin in the treatment of complicated skin and soft tissue infections (cSSTI) due to MRSA in adult subjects hospitalized for at least one day at the End of Study (EOS) visit. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to compare the bacteriological efficacy and safety and tolerability of linezolid to vancomycin in the treatment of nosocomial pneumonia due to MRSA in hospitalised adults. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Hospitalized male and female subjects with signs or symptoms consistent with infection, and if available, laboratory findings consistent with staphylococcal infection (e.g., Gram stain and culture results) 2. Subject or his/her legally acceptable representative must give informed consent by signing and dating an informed consent form prior to study entry 3. Subjects must be at least 18 years of age 4. Women of childbearing potential must use adequate contraception, defined as hormonal contraception, intrauterine device, or barrier methods (condom or vaginal diaphragm) with spermacide, throughout the study. The pre-study pregnancy test (urine or serum gonadotropin) must be negative. Women who have been surgically sterilized or are at least two years postmenopausal may be enrolled and do not have to use birth control. Women whose method of birth control is hormonal are required to use an additional barrier method during the study. 5. Subjects must be hospitalized at time of randomization 6. Subjects must be expected to survive with effective antibiotic therapy and appropriate supportive care throughout the period of treatment and follow-up 7. Subjects must be willing to complete all study related activities 8. Subjects who, after control of their acute infection, are likely to be eligible to be discharged to outpatient therapy 9. Subjects must have at least two of the specific signs and symptoms of an active skin or soft tissue infection caused by suspected MRSA that involves deep tissues such as subcutaneous tissue, fascia or skeletal muscle. Signs or symptoms may include:·purulent drainage·erythema ·swelling·induration·tenderness to palpation·pain·local warmth 10. Subjects should also have at least one of the following: · elevated body temperature: (oral >38ºC/100.4ºF), (rectal >39ºC/102.2ºF), (axillary >37.5ºC/99.5ºF), (tympanically >38.5ºC/101.3ºF) that has occurred within the last six hours· hypotension:(systolic BP<90mmHg)·elevated total peripheral white blood cell count > 10,000/mm3 15% immature neutrophils (bands) regardless of total peripheral white count 11. Subjects must have venous access available for intravenous dosing |
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E.4 | Principal exclusion criteria |
1. Subjects who have received an investigational drug during the previous 30 days or five times the plasma half-life (if known), whichever is longer or who have previously participated in this trial or any other protocol using linezolid 2. Subjects of childbearing potential, who are unable to take adequate contraceptive precautions, have a positive pregnancy test result within 24 hours prior to study entry, are otherwise known to be pregnant, or are currently breastfeeding an infant 3. Subjects with infected devices, where the device is not removed 4. Subjects with a hypersensitivity to vancomycin, oxazolidinones or any of the excipients in the IV or oral formulation of linezolid 5. Subjects with MRSA known to be resistant to either of the study drugs before study entry 6. Subjects who were treated with a previous antibiotic with MRSA activity for more than 24 hours, unless documented to be a treatment failure (72 hours of treatment and not responding). Certain drugs with variable MRSA activity (e.g. fluoroquinolones) may not be excluded if local susceptibility patterns will predict resistance and resistance is subsequently documented (see section 5.3) 7. Subjects who have received linezolid or vancomycin for more than 24 hours may not be enrolled 8. Subjects with necrotizing fasciitis, gas gangrene or osteomyelitis 9. Subjects with rapidly fatal underlying disease not expected to survive to complete the study 10. Subjects who have recent history of bone marrow transplant |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the clinical outcome at the EOS visit, in subjects with baseline MRSA. |
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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 | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
Vancomycin as comparator with Aztreonam (IV) infusion for suspected or proven Gram negative pathogen |
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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 |
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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
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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 |