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| ID | Type | Description | Link |
|---|---|---|---|
| 4360 | Registry Identifier | Netherlands Trial Register | |
| 2013-002106-31 | EudraCT Number | ||
| 836011024 | Other Grant/Funding Number | Netherlands Organisation for Health Research and Development (ZonMw) |
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Budget exceeded
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| Name | Class |
|---|---|
| ZonMw: The Netherlands Organisation for Health Research and Development | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard course | 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 |
|
| Short course | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Flucloxacillin | Drug |
|
| |
| Placebo (for flucloxacillin) |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1/2: Resolution... | Resolution of cellulitis at day 14, defined as disappearance of warmth and tenderness at the site of infection, with substantial improvement in erythema and edema | day 14 |
| Part 2/2: ...without relapse | No recurrence by day 28, defined as the need for additional antibiotic therapy for cellulitis | day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Resolution without relapse | Other operators used to define resolution at day 14 (no fever; reduction in combined erythema/edema/warmth/tenderness score of at least 2 points, or reach 0) and relapse at day 28 (no fever; stable or further improved combined score; no new antibiotics for cellulitis) | day 28 |
| Recurrence at day 90 |
| Measure | Description | Time Frame |
|---|---|---|
| Cellulitis severity score subgroup analysis | Analysis to see if the height of the cellulitis severity score influences outcome, using a regression analysis with interaction term for severity score. | up to day 28 |
| Diabetes mellitus subgroup analysis |
Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| W. Joost Wiersinga, MD, PhD | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Principal Investigator |
| Jan M. Prins, MD, PhD | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Flevoziekenhuis | Almere Stad | Flevoland | 1300EG | Netherlands | ||
| Sint Lucas Andreas Ziekenhuis |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30321312 | Derived | Cranendonk DR, Hugenholtz F, Prins JM, Savelkoul PHM, Budding AE, Wiersinga WJ; DANCE Consortium. The Skin Microbiota in Patients Hospitalized for Cellulitis and Association With Outcome. Clin Infect Dis. 2019 Apr 8;68(8):1292-1299. doi: 10.1093/cid/ciy709. | |
| 24885384 | Derived | Cranendonk DR, Opmeer BC, Prins JM, Wiersinga WJ. Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial. BMC Infect Dis. 2014 May 5;14:235. doi: 10.1186/1471-2334-14-235. |
| Label | URL |
|---|---|
| Published study protocol in BMC Infectious Diseases | View source |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 27, 2017 | Oct 9, 2017 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D002481 | Cellulitis |
| D004886 | Erysipelas |
| ID | Term |
|---|---|
| D012874 | Skin Diseases, Infectious |
| D007239 | Infections |
| D013492 | Suppuration |
| D003240 | Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D005436 | Floxacillin |
| ID | Term |
|---|---|
| D003023 | Cloxacillin |
| D010068 | Oxacillin |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 |
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| Drug |
Sugar capsule manufactured to mimic flucloxacillin 500mg capsules |
|
Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis |
| 90 days |
| Objective speed of recovery | 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 | Up to 90 days |
| Health related Quality of Life | Using questionnaires Dutch SF-36 and EQ-5D at day 1, day 28, and day 90 | Up to 90 days |
| 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. | Up to 90 days |
| Subjective speed of recovery | 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 | Up to 90 days |
| Additional antibiotic usage | Total usage of additional antibiotics for cellulitis between the end of treatment and day 90. | Up to 90 days |
| Time to relapse | Time between end of treatment and the need for additional antibiotics for cellulitis | Up to 90 days |
Analysis to see if having diabetes mellitus influences outcome, using a regression analysis with interaction term for diabetes.
| up to day 28 |
| 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. | up to 28 days |
| Per protocol analysis of the "resolution without relapse" secondary outcome | Like secondary 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. Cured is defined as above (under secondary outcome). Indeterminate is (i) receiving <80% of study drug for reasons other than unblinding/requiring new AB for cellulitis/being unable to continue due to adverse effects, (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. Patients who are not cured nor indeterminate are failures. | up to 28 days |
| Sensitivity analyses of the "resolution without relapse" secondary outcome | Similar, but requiring further improvement of symptoms by either 1 or 2 points by day 28, instead of just stability of symptoms. | up to 28 days |
| Adjustments for baseline covariates | Sensitivity analysis, adjusting the primary outcome for baseline covariates | up to day 28 |
| Amsterdam |
| North Holland |
| 1061AE |
| Netherlands |
| Slotervaartziekenhuis | Amsterdam | North Holland | 1066EC | Netherlands |
| VU university medical center | Amsterdam | North Holland | 1081HV | Netherlands |
| Onze Lieve Vrouwe Gasthuis | Amsterdam | North Holland | 1087CH | Netherlands |
| Academic Medical Center - University of Amsterdam | Amsterdam | North Holland | 1105AZ | Netherlands |
| Spaarne Gasthuis Locatie Haarlem Zuid | Haarlem | North Holland | 2035RC | Netherlands |
| Tergooi | Hilversum | North Holland | 1213XZ | Netherlands |
| St. Antonius Ziekenhuis locatie Utrecht | Utrecht | 3543AZ | Netherlands |
| Diakonessenhuis | Utrecht | 3582KE | Netherlands |
| University Medical Center Utrecht | Utrecht | 3584CX | Netherlands |
| D017437 |
| Skin and Connective Tissue Diseases |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013290 | Streptococcal Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D017192 | Skin Diseases, Bacterial |
| D012871 | Skin Diseases |
| Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |