Duration of ANtibiotic Therapy for CEllulitis

Cellulitis Clinical Trial

— DANCE  

Official title:

Duration of Antibiotic Therapy for Cellulitis (DANCE): a Randomized Controlled Trial Comparing 6 to 12 Days of Antibiotic Therapy for Patients Hospitalized With Cellulitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02032654
• Other study ID #: NL44512.018.13
• Secondary ID: 43602013-002106-
• Status: Terminated
• Phase: Phase 4
• First received: January 8, 2014
• Last updated: October 9, 2017
• Start date: August 26, 2014
• Est. completion date: September 25, 2017

Study information

• Verified date: October 2017
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 151
• Est. completion date: September 25, 2017
• Est. primary completion date: July 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cellulitis
• Erysipelas

Intervention

Drug:
• Flucloxacillin

• Placebo (for flucloxacillin)
Sugar capsule manufactured to mimic flucloxacillin 500mg capsules

Locations

Country	Name	City	State
Netherlands	Flevoziekenhuis	Almere	Flevoland
Netherlands	Academic Medical Center - University of Amsterdam	Amsterdam	Noord-Holland
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam	Noord-Holland
Netherlands	Sint Lucas Andreas Ziekenhuis	Amsterdam	Noord-Holland
Netherlands	Slotervaartziekenhuis	Amsterdam	Noord-Holland
Netherlands	VU university medical center	Amsterdam	Noord-Holland
Netherlands	Spaarne Gasthuis Locatie Haarlem Zuid	Haarlem	Noord-Holland
Netherlands	Tergooi	Hilversum	Noord-Holland
Netherlands	Diakonessenhuis	Utrecht
Netherlands	St. Antonius Ziekenhuis locatie Utrecht	Utrecht
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Diabetes mellitus subgroup analysis	Analysis to see if having diabetes mellitus influences outcome, using a regression analysis with interaction term for diabetes.	up to day 28
Other	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
Other	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
Other	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
Other	Adjustments for baseline covariates	Sensitivity analysis, adjusting the primary outcome for baseline covariates	up to day 28
Primary	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
Primary	Part 2/2: ...without relapse	No recurrence by day 28, defined as the need for additional antibiotic therapy for cellulitis	day 28
Secondary	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
Secondary	Recurrence at day 90	Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis	90 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Additional antibiotic usage	Total usage of additional antibiotics for cellulitis between the end of treatment and day 90.	Up to 90 days
Secondary	Time to relapse	Time between end of treatment and the need for additional antibiotics for cellulitis	Up to 90 days

External Links

•   Published study protocol in BMC Infectious Diseases
•   Trial website, in Dutch