E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Linezolid is an oxazolidinone antibiotic that has a broad Gram-positive antibacterial spectrum and is effective against MRSA and vancomycin-resistant Enterococcus VRE organisms. It is available in both IV and oral forms and is 100 bioavailable same IV and oral dosing . |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10040788 |
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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 at the End of Study EOS visit. |
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E.2.2 | Secondary objectives of the trial |
To compare the clinical efficacy, and safety and tolerability of linezolid to vancomycin in the treatment of cSSTI due to MRSA in adult subjects at the End of Treatment EOT visit. To compare the bacteriological efficacy, and safety and tolerability of linezolid to vancomycin in the treatment of cSSTI due to MRSA in adult subjects at the EOT and the EOS visits. To compare the medical resource utilization of linezolid and vancomycin for this subject population. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
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 in a hospital environment or in the process of referral to a hospital at the 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 or pain local warmth |
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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 in the past 6 months. 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 systemic or topical with MRSA activity other than linezolid or vancomycin for more than 24 hours and treatment extended into the 72 hour period prior to the first dose of study drug, 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 7. Subjects who were treated with linezolid or vancomycin for more than 24 hours and treatment extended into the 72 hour period prior to the first dose of study drug. Subjects who were treated with linezolid or vancomycin for the infection under study prior to this timeframe may be enrolled unless they received 72 hours or more of treatment and did not respond. 8. Subjects with known or suspected necrotizing fasciitis, gas gangrene, gangrene, septic arthritis or osteomyelitis. 9. Subjects with an infection involving a limb with evidence of critical ischemia in the affected limb defined as any of the following criteria Absent or abnormal Doppler wave forms Toe blood pressure of 45 mm Hg Ankle brachial index of 0.5 Critical ischemia as assessed by a vascular surgeon 10. Subjects with rapidly fatal underlying disease not expected to survive to complete the study. 11. Subjects who have recent history of bone marrow transplant in post-transplant hospital stay . 12. Subject with pheochromocytoma, untreated hyperthyroidism, untreated or uncontrolled hypertension, or carcinoid syndrome. 13. Subject with known or suspected meningitis or endocarditis. 14. Subject who has clinical AIDS or a CD4 cell count 200 cells/mm3 secondary to HIV infection. 15. Subjects with sustained shock, defined as systolic blood pressure 90 mm Hg for 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure. 16. Subjects who have medical conditions in which inflammation may be prominent for an extended period even after successful bacterial eradication, e.g., superinfected eczema or atopic dermatitis . 17. Subjects with uncomplicated skin or superficial skin structure infection such as superficial/simple cellulitis, impetiginous lesion, furuncle, or simple abscess that only need surgical drainage for cure. 18. Subjects from whom a culture cannot be obtained. 19. Subjects with self-limited infections such as isolated folliculitis or other infection that has a high surgical incision cure rate or furunculosis that is not associated with erythema of at least 5 cm in radius. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical and microbiologic evaluations will be performed for each subject to assess efficacy. The variables will include clinical observations of infection, changes in vital signs and signs/symptoms, number of days of study medication received, and microbiologic assessment of the infection site. The primary efficacy endpoint will be the clinical outcome at the EOS visit, in subjects with baseline MRSA. The secondary efficacy endpoints will be the microbiological outcome at the EOT and EOS visits, for subjects with baseline MRSA and the subject s clinical outcome at the EOT visit. Safety and tolerability will be assessed in subjects with baseline MRSA at the EOT and EOS visits. The secondary endpoints for medical resource utilization will include length of hospital stay, duration of IV study medication and inpatient and outpatient medical resource utilization. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | 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) | No |
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 | 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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |