E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Acute Bacterial Skin Infection (ABSSSI) |
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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 the non-inferiority of oral flucloxacillin alone (monotherapy) compared with a combination of oral flucloxacillin and phenoxymethylpenicillin (dual therapy) for the ED- directed outpatient treatment of cellulitis. |
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E.2.2 | Secondary objectives of the trial |
To measure adherence and persistence of trial patients with outpatient antibiotic therapy measured by self-report and counting the number of unused study medications at the end of treatment visit. In addition, to describe adherence and persistence in a sub-study using an electronic medication event monitoring system (MEMS®) II. To perform a within-trial evaluation of the cost per QALY gained from the use of oral flucloxacillin compared with combination therapy over a one-month time horizon from the perspective of the health-care payer (direct costs). In a secondary analysis the perspective will be extended to consider costs related to the intervention falling on the patient and government. III. To externally validate the ESTI-score, a HRQL questionnaire designed to quantify the impact of cellulitis on patient HRQL in clinical trials.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The study design includes a sub-study to evaluate both adherence to therapy using an electronic monitoring system (MEMS) and persistence to therapy within the trial. The purpose of this is to both describe these parameters in the understudied area of short course outpatient antibiotic treatment as well as providing evidence for any adjustments in analysis based on medication taking behaviour. The objectives of the sub-study is to measure adherence and persistence of trial patients with outpatients antibiotic therapy measure by self report and counting the number of unused study medication at the end of treatment visit. In addition, to describe adherence and persistence in a sub-study using electronic medication event monitoring system (MEMS) |
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E.3 | Principal inclusion criteria |
1. Clinically diagnosed cellulitis, wound infection & abscess affecting any body part, excluding the perineum, and having any two of the following signs: •Erythema •Warmth •Tenderness / Pain of affected area •Oedema / Induration •Regional lymphadenopathy •Purulent drainage 2. Cellulitis, wound infection & abscess deemed treatable with oral antibiotics on an outpatient basis 3. Patients with cellulitis, wound infection & abscess who have no signs of systemic toxicity and have no uncontrolled co-morbidities. 4. Written informed consent obtained. 5. 16 years of age or older. 6. Fluency in written and spoken English. 7. Willing to return for study follow-up or to have the research nurse or clinical project coordinator visit them. 8. Willing to receive a telephone call from a study investigator.
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E.4 | Principal exclusion criteria |
1. Penicillin allergy (self-reported or confirmed). 2. Any cellulitis wound infection & abscess that treating clinicians deem treatable with intravenous (IV) antibiotics. 3. 3. Patients that may have a significant systemic upset such as acute confusion, tachycardia, tachypnoea, hypotension or may have unstable co-morbidities that may interfere with a response to therapy or have a limb threatening infection due to vascular compromise. 4. Patients who may have a severe life threatening infection such as necrotizing fasciitis. 5. Any cellulitis wound infection & abscess of the perineal region. 6. Patients who have received more than 24 hours of effective antibiotics for the current episode of acute cellulitis, wound infection & abscess 7. Any medical condition, based on clinical judgment that may interfere with the interpretation of the primary outcome measures (e.g. a chronic skin condition at the site of the cellulitis wound infection or abscess). 8. Immunodeficiency from primary or secondary causes (e.g. corticosteroids, chemotherapeutic agents). 9. Previous history of renal dysfunction or known chronic kidney disease under the care of a nephrologist.
10. Previous history of liver dysfunction defined as chronically deranged liver function tests elicited from the medical notes or history. 11. Suspected or confirmed septic arthritis. 12. Suspected or confirmed osteomyelitis. 13. Infection involving prosthetic material. 14. Pregnant or lactating women. 15. Patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction 16. Patients with a previous history of methicillin-resistant staphylococcus aureus (MRSA) colonisation/infection. 17. Patients with lactose intolerance diagnosed by a medical professional. 18. Patients currently taking probenecid, neomycin, chloramphenicol, erythromycin , tetracyclines sulfinpyrazone, methotrexate, guar gum or an oral anticoagulant.
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E.5 End points |
E.5.1 | Primary end point(s) |
i. A suitably trained member of the study team will determine clinical cure at the TOC visit. This is a clinically-determined response to treatment based on the judgment of a suitably trained member of the study team. ii. Definition of clinical cure: a. No treatment failure at any previous visit b. Resolution or minimal presence of the following signs and symptoms from the baseline assessment based on the study investigators clinical assessment i. Erythema ii. Swelling iii. Tenderness iv. Induration
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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) |
The principle secondary outcome measure is a ≥ 20% reduction in lesion surface area on day 2-3 after enrolment compared to the baseline visit. In addition, the following secondary outcome measures will be assessed: 1. Clinical treatment failure at each follow-up visit 2. Adherence and persistence of trial patients with outpatient antibiotic therapy at EOT (day 8-10 post enrolment). 3. HRQL assessments at each follow-up visit. 4. A pharmaco-economic assessment of cost per QALY.
ECR measured on day 2-3 is defined as i. ≥20% reduction in the lesion surface area from that which was measured at enrolment. ii. Objective measurement of lesion size is the US-FDA recommended outcome measure of choice. In order to enhance the validity of the study findings, an objective measure of the percentage decrease in the diameter of infection at day 2-3 will be utilized as a secondary outcome measure. iii. Surface area measurement will be achieved by multiplying the vertical and horizontal measurements of the lesion.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 2-3 post enrolment Day 8-10 Post enrolment and Day 14-21 Post enrolment |
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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 | 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 | 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) | 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 | 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.8.2.4 | 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 | 5 |
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 | 20 |
E.8.9.1 | In the Member State concerned days | |