E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cellulitis (Cellulitis is a common acute, spreading pyogenic inflammation of the skin (dermis) and subcutaneous tissue, usually complicating a wound, ulcer or dermatosis) |
Bacteriele huidinfecties |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
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 determine whether 6 days of flucloxacillin has equal efficacy compared to 12 days in patients hospitalized with cellulitis who after 5 days of initial therapy have substantially improved, defined as absence of fever (temp > 38.0°C) and improvement in cellulitis severity score (self-reported or investigator assessed). |
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E.2.2 | Secondary objectives of the trial |
- To assess differences in the frequency of relapse by day 90 - To assess differences in (A) speed of improvement of symptoms and (B) quality of life - To assess the effects of 6 days of antibiotics compared to 12 days on total antibiotic use and health care costs - To analyse inflammation parameters in the (epi)dermis and blood during cellulitis, to explore markers of disease severity and determinants of therapeutic failure |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria. Subjects must be: - Admitted to the hospital to receive intravenous antibiotics for cellulitis/erysipelas. Cellulitis is the general the general descriptive term suggesting infection and indicating the warmth, erythema and induration of skin and/or subcutaneous tissue, with or without pain (this also includes erysipelas, see appendix I). - 18 years of age or older - Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form |
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E.4 | Principal exclusion criteria |
As this study focuses on the treatment of cellulitis requiring hospitalization without additional complicating factors, a potential subject who meets any of the following criteria will be excluded from participation: - Allergy for flucloxacillin, other beta-lactam antibiotics or one of the additives, or flucloxacillin induced hepatitis or liver enzyme disorders - Concurrent use of antibiotics for other indications - Alternative diagnosis accounting for the clinical presentation. - All cases involving any of the following complicating factors: o Use of antibiotics with Gram-positive activity for more than 4 days in the past 7 days o Intensive care unit admission during the last 7 days o Risk factors associated with Gram-negative pathogens as a causative agent19: o Chronic or macerated infra-malleolar ulcers, or infra-malleolar ulcers with previous antibiotic treatment, in patients with diabetes mellitus 20 o Neutropenia o Cirrhosis (Child-Pugh class B or C) o Intravenous drug use o Human or animal bite o Skin laceration acquired in fresh or salt open water o Fish fin or bone injuries o Severe peripheral arterial disease (Fontaine IV) o Severe cellulitis necessitating surgical debridement or fascial biopsy o Necrotizing fasciitis o Periorbital or perirectal involvement o Surgery o Life expectancy less than one month
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is resolution of cellulitis at 14 days, defined as disappearance of warmth and tenderness at the site of infection, with substantial improvement in erythema and edema, and without recurrence by day 28, defined as the need of additional antibiotic therapy for cellulitis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Recurrence of cellulitis by day 90 after inclusion, defined as the need of additional antibiotic therapy for cellulitis • Speed of recovery, as determined by improvement in cellulitis severity score, and self assessment of subjective pain and swelling on Visual Analog Scales scales (0-10), assessed at baseline (day 0), days 2-3, 5-6, 14, 28 and 90 (day 90 self-assessment only)12 • Mean health-related Quality of Life (using the Dutch SF-36 questionnaire and the EQ-5D) at day 0, 28 and 90. • Health care resource utilisation, as determined by total antibiotic use and effect on direct and indirect health-care associated costs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 0, 2-3, 5-6, 14, 28, 90. |
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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 | Yes |
E.6.4 | Safety | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |