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Duration of ANtibiotic Therapy for CEllulitis (DANCE)

Primary Purpose

Cellulitis, Erysipelas

Status
Terminated
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Flucloxacillin
Placebo (for flucloxacillin)
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cellulitis focused on measuring antibiotics, flucloxacillin, therapy duration, cellulitis, erysipelas, skin infections, hospital

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Flevoziekenhuis
  • Sint Lucas Andreas Ziekenhuis
  • Slotervaartziekenhuis
  • VU university medical center
  • Onze Lieve Vrouwe Gasthuis
  • Academic Medical Center - University of Amsterdam
  • Spaarne Gasthuis Locatie Haarlem Zuid
  • Tergooi
  • St. Antonius Ziekenhuis locatie Utrecht
  • Diakonessenhuis
  • University Medical Center Utrecht

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard course

Short course

Arm Description

Flucloxacillin (1000mg iv OR, later, 500mg capsules), every 6 hours, for 6 days, followed by: Flucloxacillin 500mg capsules, every 6 hours, for 6 days

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

Outcomes

Primary Outcome Measures

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
Part 2/2: ...without relapse
No recurrence by day 28, defined as the need for additional antibiotic therapy for cellulitis

Secondary Outcome Measures

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)
Recurrence at day 90
Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis
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
Health related Quality of Life
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
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
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

Full Information

First Posted
January 8, 2014
Last Updated
October 9, 2017
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT02032654
Brief Title
Duration of ANtibiotic Therapy for CEllulitis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Why Stopped
Budget exceeded
Study Start Date
August 26, 2014 (Actual)
Primary Completion Date
July 24, 2017 (Actual)
Study Completion Date
September 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cellulitis, Erysipelas
Keywords
antibiotics, flucloxacillin, therapy duration, cellulitis, erysipelas, skin infections, hospital

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard course
Arm Type
Active Comparator
Arm Description
Flucloxacillin (1000mg iv OR, later, 500mg capsules), every 6 hours, for 6 days, followed by: Flucloxacillin 500mg capsules, every 6 hours, for 6 days
Arm Title
Short course
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Flucloxacillin
Other Intervention Name(s)
Floxapen
Intervention Type
Drug
Intervention Name(s)
Placebo (for flucloxacillin)
Intervention Description
Sugar capsule manufactured to mimic flucloxacillin 500mg capsules
Primary Outcome Measure Information:
Title
Part 1/2: Resolution...
Description
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
Time Frame
day 14
Title
Part 2/2: ...without relapse
Description
No recurrence by day 28, defined as the need for additional antibiotic therapy for cellulitis
Time Frame
day 28
Secondary Outcome Measure Information:
Title
Resolution without relapse
Description
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)
Time Frame
day 28
Title
Recurrence at day 90
Description
Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis
Time Frame
90 days
Title
Objective speed of recovery
Description
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
Time Frame
Up to 90 days
Title
Health related Quality of Life
Description
Using questionnaires Dutch SF-36 and EQ-5D at day 1, day 28, and day 90
Time Frame
Up to 90 days
Title
Health care resource utilisation
Description
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.
Time Frame
Up to 90 days
Title
Subjective speed of recovery
Description
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
Time Frame
Up to 90 days
Title
Additional antibiotic usage
Description
Total usage of additional antibiotics for cellulitis between the end of treatment and day 90.
Time Frame
Up to 90 days
Title
Time to relapse
Description
Time between end of treatment and the need for additional antibiotics for cellulitis
Time Frame
Up to 90 days
Other Pre-specified Outcome Measures:
Title
Cellulitis severity score subgroup analysis
Description
Analysis to see if the height of the cellulitis severity score influences outcome, using a regression analysis with interaction term for severity score.
Time Frame
up to day 28
Title
Diabetes mellitus subgroup analysis
Description
Analysis to see if having diabetes mellitus influences outcome, using a regression analysis with interaction term for diabetes.
Time Frame
up to day 28
Title
Per protocol analysis
Description
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.
Time Frame
up to 28 days
Title
Per protocol analysis of the "resolution without relapse" secondary outcome
Description
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.
Time Frame
up to 28 days
Title
Sensitivity analyses of the "resolution without relapse" secondary outcome
Description
Similar, but requiring further improvement of symptoms by either 1 or 2 points by day 28, instead of just stability of symptoms.
Time Frame
up to 28 days
Title
Adjustments for baseline covariates
Description
Sensitivity analysis, adjusting the primary outcome for baseline covariates
Time Frame
up to day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
W. Joost Wiersinga, MD, PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jan M. Prins, MD, PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Flevoziekenhuis
City
Almere
State/Province
Flevoland
ZIP/Postal Code
1300EG
Country
Netherlands
Facility Name
Sint Lucas Andreas Ziekenhuis
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1061AE
Country
Netherlands
Facility Name
Slotervaartziekenhuis
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1066EC
Country
Netherlands
Facility Name
VU university medical center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1081HV
Country
Netherlands
Facility Name
Onze Lieve Vrouwe Gasthuis
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1087CH
Country
Netherlands
Facility Name
Academic Medical Center - University of Amsterdam
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105AZ
Country
Netherlands
Facility Name
Spaarne Gasthuis Locatie Haarlem Zuid
City
Haarlem
State/Province
Noord-Holland
ZIP/Postal Code
2035RC
Country
Netherlands
Facility Name
Tergooi
City
Hilversum
State/Province
Noord-Holland
ZIP/Postal Code
1213XZ
Country
Netherlands
Facility Name
St. Antonius Ziekenhuis locatie Utrecht
City
Utrecht
ZIP/Postal Code
3543AZ
Country
Netherlands
Facility Name
Diakonessenhuis
City
Utrecht
ZIP/Postal Code
3582KE
Country
Netherlands
Facility Name
University Medical Center Utrecht
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
30321312
Citation
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.
Results Reference
derived
PubMed Identifier
24885384
Citation
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.
Results Reference
derived
Links:
URL
http://www.biomedcentral.com/1471-2334/14/235
Description
Published study protocol in BMC Infectious Diseases

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Duration of ANtibiotic Therapy for CEllulitis

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