The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613001366741
Ethics application status
Approved
Date submitted
6/12/2013
Date registered
13/12/2013
Date last updated
13/12/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
The safety and efficacy of short course intravenous antibiotic therapy for the resolution of acute cellulitis and erysipelas
Scientific title
Randomised controlled trial of 24 hours intravenous (IV) antibiotic therapy followed by oral antibiotic therapy versus 72 hours or more IV antibiotic therapy for the successful resolution of acute erysipelas and cellulitis of the lower limb
Secondary ID [1] 283708 0
Nil known
Universal Trial Number (UTN)
Trial acronym
SWITCH trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cellulitis of the lower limb 290674 0
Erysipelas of the lower limb 290709 0
Condition category
Condition code
Infection 291044 291044 0 0
Other infectious diseases
Skin 291078 291078 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
24 hours intravenous antibiotic therapy followed by oral antibiotics to a maximum of 10 days.
Intravenous antibiotics: We recommend flucloxacillin 2 grams given over 20-30 minutes every 6 hours, or cephazolin 2 grams given over 20-30 minutes 2-3 times daily (2 times daily if given at home, or 3 times daily if given in the hospital). Any antibiotic with acitvity against Steptococcus and Staphylococcus spp. is however allowable. The antibiotic used may differ according to patient allergies, but not physician discretion.
Following 24 hours of intravenous therapy patients are switched to oral antibiotics for 9 days. Total duration of antibiotics is 10 days.
Oral antibiotics: flucloxacillin 500 mg 4 times daily or cephalexin 500 mg 4 times daily. These medicines are administered by the patient, but are approximately at 6 hour intervals. Any antibiotic with acitvity against Steptococcus and Staphylococcus spp. is however allowable depending on patient allergies.

Adherence to oral treatment is determined by drug tablets remaining at study visits at days 3-4 and 7-10.
Intervention code [1] 288403 0
Treatment: Drugs
Comparator / control treatment
72 hours or more intravenous antibiotic therapy determined by clinician preference followed by oral antibiotics to a maximum of 10 days.
Intravenous antibiotics: We recommend flucloxacillin 2 grams 4 tines daily infused over 20-30 minutes, or cephazolin 2 grams infused over 20-30 minutes, 2-3 times daily. Antibiotics are administered twice daily if patients are at home, or 3 times daily if they are in hospital. Any antibiotic with acitvity against Steptococcus and Staphylococcus spp. is however allowable depending on patient allergies but not according to physician discretion.

Following 72 hours or more of intravenous therapy patients are switched to oral antibiotics for the number of days remaining after IV therapy to total 10 days.
Oral antibiotics: flucloxacillin 500 mg 4 times daily or cephalexin 500 mg 4 times daily.
Any antibiotic with acitvity against Steptococcus and Staphylococcus spp. is however allowable depending on patient allergies.

Adherence to oral treatment is determined by drug tablets remaining at study visits at days 7-10.
Control group
Active

Outcomes
Primary outcome [1] 291035 0
Resolution of cellulitis, defined by all of the following 3 criteria:
Resolution of fever at visit 2 (72-96 hours).
Absence of progression of skin & subcutaneous abnormalities at visit 2.
Absence of ongoing requirement for antibiotic therapy beyond the study period of 10 days.
Timepoint [1] 291035 0
10 days
Secondary outcome [1] 305869 0
Self-reported pain using Wong-Baker face scale
Timepoint [1] 305869 0
Assessed daily by participants for 7-10 days and marked on their patient study diary.
Secondary outcome [2] 305943 0
Clinical resolution of erysipelas or cellulitis measured by blinded photographic assessment of affected lower limb
Timepoint [2] 305943 0
Assessed at 3-4 days and 7-10 days at study visits when photos are taken and later compared with the photo of the affected area on recruitment by a blinded reviewer.
Secondary outcome [3] 305944 0
Adverse events include reactions to an antibiotic, such as a rash, or diarrhoea, or an infected intravenous cannula in the setting of intravenous therapy. All antibiotics administered intravenously are first administered in the hospital setting to observe patients for allergic reactions. Patients on intravenous antibiotics at home are reviewed twice daily at home, where they are asked about any new symptoms, and their cannula is inspected for signs of infection. Patients who are on oral antibiotics at home are reviewed at visits 2 (days 3-4) and 3 (days 7-10), and are asked to contact study coordinators if they develop any reactions.
Timepoint [3] 305944 0
10 days
Secondary outcome [4] 305945 0
Disease recurrence within 30 days will be assessed via a telephone follow-up at day 30, where patients are questioned about their recovery and any recurrence of cellulitis since their 3rd visit at days 7-10.
Timepoint [4] 305945 0
30 days

Eligibility
Key inclusion criteria
1. Spontaneous cellulitis or erysipelas of lower limb with consistent clinical features, including erythema, pain, swelling of lower extremity of acute onset with associated fevers and/or chills, rigors, and nausea
2. Age greater than or equal to18 years
3. Antibiotics effective against cellulitis <24-48 hours
4. Patient is planned for intravenous treatment for cellulitis of the lower limb
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age <18 years
2. Pregnant female
3. Immunosuppression including any one of: active chemotherapy in the last 6 weeks, receipt of prednisolone >20mg/ day, or neutropaenia with neutrophil count <0.5 x 109/L or alternative conditions significantly affecting the immune system
4. Alternative diagnosis, including but not limited to: venous eczema, Diabetic foot infection, Surgical site (wound) infection or other open wound
5. Penetrating injury or bite
6. Suspected complication such as abscess or necrotising infection
7. Septic shock or other reasons for intensive care unit admission
8. Oral antibiotics effective against cellulitis for > 48 hours or IV antibiotics effective against cellulitis for >24 hours. (including receipt of flucloxacillin, dicloxacillin, cephalexin, cephazolin, clindamycin and Vancomycin).
9. Patient unwilling to participate or in the opinion of investigators will be unable to comply with the requirements of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Individuals who are identified as potential participants will be screened for eligibility and allocated a sequential screening number. Eligible participants who wish to participate and do not fulfil any exclusion criteria will be consented to participate and allocated a sequential randomisation number. Randomisation for the study will be performed prior to the initiation of participant recruitment via random block allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation of participants to either the short-course or standard course treatment arms of the study will be completed on enrolment into the study. Participants will be allocated the envelope with the lowest available study number, and allocation will then occur in ascending numeric order.
Sequentially numbered, opaque, tamper-evident envelopes will contain a slip with the treatment allocation. The participant’s basic information including initials, unique study number and date of birth will be entered on this slip, and the number on the envelope will indicate the unique study number for that participant. A separate master list will be maintained containing the 8 digit participant number and initials, date of birth and hospital UR number of the participant.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Non-inferiority of short-course treatment will be assessed by comparing the tail of a 95% confidence interval for the difference in the proportions of successful resolution of cellulitis between the two treatment arms, with the stated non-inferiority margin of 10%.
Sample size is calculated based on the one-sided hypothesis test for the difference of two proportions. Assuming an efficacy rate of 90% for both treatment arms, a one-sided significance of 2.5% and 80% power, to reject the null hypothesis of inferiority with a margin of 10% requires a sample size of at least 284 (142 in each arm).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1805 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 7620 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 288390 0
Government body
Name [1] 288390 0
Victorian Department of Health
Address [1] 288390 0
50 Lonsdale Street
Melbourne, 3000
Victoria, Australia
Country [1] 288390 0
Australia
Primary sponsor type
Hospital
Name
Barwon Health
Address
Bellerine St, Geelong
Vic 3220
Country
Australia
Secondary sponsor category [1] 287092 0
None
Name [1] 287092 0
Address [1] 287092 0
Country [1] 287092 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290276 0
Barwon Health Human research and Ethics Committee
Ethics committee address [1] 290276 0
Kitchener House
Geelong Hospital
Ryrie st, Geelong
VIC 3220
Ethics committee country [1] 290276 0
Australia
Date submitted for ethics approval [1] 290276 0
04/06/2012
Approval date [1] 290276 0
04/09/2012
Ethics approval number [1] 290276 0
12/63

Summary
Brief summary
Cellulitis and erysipelas are common skin infections, and it is not known what the ideal duration of IV therapy is for treatment. This is a trial which commenced at Barwon Health in November 2012 is provisionally planned for expansion to multiple sites in Australia to study whether a short-course of IV therapy is not inferior to longer duration IV therapy. Over 300 participants are required for this trial.

Patients who attend Geelong hospital emergency department, hospital wards, or hospital in the home (HITH) programs with a diagnosis of cellulitis and are planned for IV therapy are currently reviewed to determine if they fulfill the criteria for inclusion in the trial. Those who meet the criteria and agree to participate are consented to participation in the trial, and are then randomly allocated to either IV therapy of 72 hours or more (as an inpatient or on hospital in the home) or 24 hours IV therapy, both followed by oral therapy for a maximum of 10 days. Antibiotics that are used are those ordinarily recommended for cellulitis and are not experimental.

Each participant is involved for approximately one month, including 3 visits over the first 10 days and a follow-up phone contact at Day 30. In order to determine that short course IV therapy is safe and effective when compared to longer durations, we measure the following things to determine that cellulitis has resolved:
1) That fever has resolved at 72-96 hours
2) That skin abnormalities have not gotten worse at Days 7-10
3) That ongoing antibiotic therapy is not required after 10 days.
We also measure; time taken for fever to resolve, pain as reported by the patient, photos of the affected leg over the first 10 days, and whether there are any side effects that patients experience while on this trial. At 30 days the patient is telephoned to check that their cellulitis has not recurred.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44762 0
Dr N. Deborah Friedman
Address 44762 0
Department of Medicine
Myers House
Geelong Hospital
Bellerine St, Geelong
VIC 3220
Country 44762 0
Australia
Phone 44762 0
+61342152033
Fax 44762 0
Email 44762 0
Deborahf@barwonhealth.org.au
Contact person for public queries
Name 44763 0
Dr N. Deborah Friedman
Address 44763 0
Department of Medicine
Myers House
Geelong Hospital
Bellerine St, Geelong
VIC 3220
Country 44763 0
Australia
Phone 44763 0
+61342152033
Fax 44763 0
Email 44763 0
Deborahf@barwonhealth.org.au
Contact person for scientific queries
Name 44764 0
Dr N. Deborah Friedman
Address 44764 0
Department of Medicine
Myers House
Geelong Hospital
Bellerine St, Geelong
VIC 3220
Country 44764 0
Australia
Phone 44764 0
+61342152033
Fax 44764 0
Email 44764 0
Deborahf@barwonhealth.org.au

No information has been provided regarding IPD availability
Summary results
No Results