There is no difference in outcomes when patients hospitalized with cellulitis are treated with either a short-course (6 days) or standard-course (12 days) of antibiotics.
ID
Source
Brief title
Health condition
cellulitis, erysipelas
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
- Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis
- Objective speed of recovery, measured by improvement in cellulitis severity score (a 7 item scoring system, each with a score between 0-3; items are erythema, warmth, tenderness, edema, ulceration, drainage and fluctuance). Determined at day 1, day 2-3, day 5-6, day 14, and day 28
- Quality of Life scores, using questionnaires Dutch SF-36 and EQ-5D at day 1, day 28, and day 90
- Health care resource utilisation, determined by total antibiotic use and effect on direct and indirect health-care associated costs, using modified versions of iMTA's Productivity Cost Questionnaire (iPCQ) and Medical Consumption Questionnaire (iMCQ). Measured at day 5-6, day 28 and day 90.
- Subjective speed of recovery, using visual Analog Scales (0-10) on pain and on swelling. Determined at day 1, day 2-3, day 5-6, day 14, day 28, and day 90
- Additional antibiotic usage, measuring total usage of additional antibiotics for cellulitis between the end of treatment and day 90.
- Time to relapse; time between end of treatment and the need for additional antibiotics for cellulitis
Additional analyses:
Cellulitis severity score subgroup analysis, to see if the height of the cellulitis severity score influences outcome, using a regression analysis with interaction term for severity score.
Diabetes mellitus subgroup analysis, to see if having diabetes mellitus influences outcome, using a regression analysis with interaction term for diabetes.
Per protocol analysis: like main outcome, but the following will be included: (i) patients with treatment failure, who have received at least 24 hours of study medication, and (ii) patients with treatment success, who have received at least 80% of study medication. Treatment failure is defined as the persistence or progression of signs and symptoms of the acute process after randomization, or the inability to complete the study owing to adverse events. The response is deemed indeterminate when the patients (i) received less than 80% of the study drug for reasons other than treatment failure, (ii) acquired a concomitant infection outside of the skin requiring antibiotic treatment, (iii) were lost to follow-up, or (iv) died unrelated to the primary diagnosis.
Adjustments for baseline covariates: sensitivity analysis, adjusting the primary outcome for baseline covariates
Background summary
Cellulitis is among the most common infections leading to hospitalization, yet the optimal duration of therapy remains ill defined. Pragmatically, Dutch guidelines advise 10-14 days of antibiotics, which is the current standard of care. Recently it has been shown that antibiotic treatment for pneumonia and urinary tract infections can safely and significantly be shortened. Importantly, in an outpatient setting, treatment of uncomplicated cellulitis with 5 days of antibiotics was as effective as 10 days. We hypothesize that there is no difference in outcomes when patients hospitalized with cellulitis are treated with either a short-course (6 days) or standard-course (12 days) of antibiotics.
Study objective
There is no difference in outcomes when patients hospitalized with cellulitis are treated with either a short-course (6 days) or standard-course (12 days) of antibiotics.
Study design
Visits scheduled for day 1, day 2-3, day 5-6, day 14, day 28, and day 90.
Intervention
Patients are included on day 1 of their hospital cellulitis episode, and judged on eligiblity for randomization on day 5-6. To qualify for randomization, patients must respond to therapy, defined as absence of fever (temp > 38.0°C) and improvement in cellulitis severity score (see below). Arm 1: Short course (6 days antibiotics, 6 days placebo), experimental Flucloxacillin (1000mg iv OR, later, 500mg capsules), every 6 hours, for 6 days, followed by: Placebo (for flucloxacillin 500mg) 500mg capsules, every 6 hours, for 6 days Arm 2: Standard course (12 days antibiotics), active comparator Flucloxacillin (1000mg iv OR, later, 500mg capsules), every 6 hours, for 6 days, followed by: Flucloxacillin 500mg capsules, every 6 hours, for 6 days
Meibergdreef 9
D.R. Cranendonk
Amsterdam 1105 AZ
The Netherlands
+31 20 566 5247
d.r.cranendonk@amc.uva.nl
Meibergdreef 9
D.R. Cranendonk
Amsterdam 1105 AZ
The Netherlands
+31 20 566 5247
d.r.cranendonk@amc.uva.nl
Inclusion criteria
- Admitted to receive intravenous antibiotics for cellulitis/erysipelas
- 18 years of age or older
- Capable of giving written informed consent, able to comply with study requirements and restrictions
Exclusion criteria
- 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:
-- Use of antibiotics with Gram-positive activity for more than 4 days in the past 7 days
-- Intensive care unit admission during the last 7 days
-- Severe peripheral arterial disease (Fontaine IV)
-- Severe cellulitis necessitating surgical debridement or fascial biopsy
-- Necrotizing fasciitis
-- Periorbital or perirectal involvement
-- Surgery
-- Life expectancy less than one month
-- Risk factors associated with Gram-negative pathogens as a causative agent:
--- Chronic or macerated infra-malleolar ulcers, or infra-malleolar ulcers with previous antibiotic treatment, in patients with diabetes mellitus.
--- Neutropenia
--- Cirrhosis (Child-Pugh class B or C)
--- Intravenous drug use
--- Human or animal bite
--- Skin laceration acquired in fresh or salt open water
--- Fish fin or bone injuries
Design
Recruitment
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL4208 |
| NTR-old | NTR4360 |
| ClinicalTrials.gov | NCT02032654 |
| CCMO | NL44512.018.13 |
| OMON | NL-OMON45002 |