A Randomised Controlled Trial on Public Information Provision
PILOT RANDOMISED CONTROLLED TRIAL OF SHORT …
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OUR VALUES / RESPECT / COMPASSION / COMMITMENT / ACCOUNTABILITY / INNOVATION PILOT RANDOMISED CONTROLLED TRIAL OF SHORT COURSE INTRAVENOUS ANTIBIOTIC THERAPY FOR ERYSIPELAS AND CELLULITIS OF THE LOWER LIMB (SWITCH TRIAL) Friedman ND 1 , Pollard J 1,2 , Walton AL 1 , O’Brien DP 1 , Cowan R 1 , Lim K 1 , Huffam S 1 , Lane S 3 , Simpson P 1 , Hughes AJ 1 , Athan E 1 . Department of Infectious Diseases 1 , Hospital in the Home Service 2 , Biostatistics unit 3 , Barwon Health, Geelong, Victoria, Australia. METHODS Design: Randomized, controlled, open label, single-site pilot trial. Target Enrolment: 40 patients. Consecutive eligible patients were randomised by random block allocation to the intervention arm of 24 hours IV therapy or the control arm of ≥ 72 hours IV therapy (both followed by oral therapy to total duration 7-10 days). IV antibiotics used were anti-staphylococcal penicillins and first generation cephalosporins. Oral agents included; di/flucloxacillin, cephalexin, clindamycin. Illustration of Study Design: CONCLUSIONS • This pilot randomized trial of short course therapy for cellulitis has determined that such a trial is feasible. • It is very common for patients to present to hospital for IV treatment of presumed cellulitis after receiving >48 hours of oral antibiotics. • Enrolment into this trial with strict inclusion & exclusion criteria has been slow to date with less than 20% of screened patients being recruited. • Recruitment was further marred by many conditions that are mislabelled as cellulitis. • Among recruited trial patients to date, efficacy in both groups has been in keeping with expectations with regard to the non-inferiority design. • No safety issues have been identified to date. • This well-designed randomised clinical trial with strict inclusion and exclusion criteria that will lead to results of high validity. • A single trial site will be unable to recruit the required number of participants within an acceptable timeframe. • The SWITCH trial is expanding into a multi-centre study in Australia and Zealand in 2014. • Participants will no longer be excluded based on receiving oral antibiotics prior to recruitment. Photographic assessment of the affected limb at visits 1, 2, & 3: ACKNOWLEDGEMENTS This project has been funded by a grant from Department of Health, Victoria. [email protected] Barwon Health Geelong, VIC, Australia Inclusion Criteria • Spontaneous cellulitis of lower limb with consistent clinical features, including; erythema, pain, and swelling with onset within 48 hours with either fever on clinical examination or history consistent with fevers and/or chills, rigors, nausea within 48 hours prior to presentation • Age > 18 years • Patient is planned for hospital admission or hospital-in-the-home IV treatment for cellulitis of the lower limb Exclusion Criteria • Age <18 yrs or Pregnant Female • Immunosuppression • Alternative diagnosis, including venous eczema, Diabetic foot infection, Surgical site (wound) infection or other open wound • Penetrating injury or bite • Suspected complication such as abscess or necrotising infection • Septic shock or other reasons for intensive care unit admission • Antibiotics effective against cellulitis for > 48 hours orally or > 24 hours IV • Patient unwilling to participate or in the opinion of investigators will be unable to comply INTRODUCTION & PURPOSE Cellulitis is a common skin and soft tissue infection with an incidence of 16.4-24.6/1000 person-years. Cellulitis and erysipelas can be differentiated according to the tissues affected; erysipelas affects the upper dermis, including the superficial lymphatics, while cellulitis involves the deeper dermis, and subcutaneous fat. The most common causative organism is Streptococcus spp. and the infections that result carry an excellent prognosis. Although antibiotics are the mainstay of therapy for erysipelas and cellulitis, to date there is no consensus on whether intravenous or oral therapy are optimal choices, and the suggested duration of therapy. This randomized controlled non-inferiority trial was undertaken to determine the safety and efficacy of 24 hours intravenous (IV) antibiotic therapy compared to 72 hours or more of IV antibiotic therapy (both followed by oral therapy) for the treatment of cellulitis and erysipelas. Australian and New Zealand Clinical Trial Registry ANZCTR Number 365426. We hypothesize that short-course IV therapy is not inferior to longer duration IV therapy for the treatment of cellulitis and erysipelas. RESULTS Over a 12 month period from November 2012, 243 patients were screened for participation in the SWITCH trial. 40 patients were recruited to the pilot trial (16%) and 203 patients (84%) fulfilled one or more exclusion criteria. The majority of patients were excluded based on having received oral antibiotics for >48 hours prior to presentation at our institution. Many other patients were excluded based on an alternative diagnosis including venous eczema, diabetic foot infection and infected surgical wounds. Approximately 9% of excluded patients either decided not to participate, or were deemed to be unlikely to be able to comply with the study. 20 patients were randomized to ≥72 hours IV therapy; 19 successfully responded to therapy and 1 case withdrew prematurely. 20 patients were randomized to 24 hours IV therapy; 17 responded successfully and 3 withdrew prematurely. 1 of these patients was withdrawn because of ICU admission. 1 patient developed self-limiting, non C.difficile diarrhea after visit 3. There were no other adverse events. A retrospective review of 12 months of cellulitis cases in 2011-2012 revealed that 59 of 265 cases of cellulitis (22%) would have met criteria for inclusion in this trial. Primary Outcome Measures: Resolution of cellulitis, defined by the following 3 criteria: 1) Absence of progression of skin & subcutaneous abnormalities at visit 2 2) Resolution of fever at visit 2 3) Absence of ongoing requirement for antibiotic therapy beyond study period of 10 days. Secondary Outcome Measures: 1) Assessment of self-reported pain using Wong-Baker face scale 2) Blinded photographic assessment of affected limb 3) Adverse events 4) Disease recurrence within 30 days Patient Identification & Eligibility Assessment Vist 3 (Day 7-10) Vist 2 (Day 3-4) Consent & Randomisation Visit 1 (Day 0) Follow Up Phone Contact (Day 30) Screening - 24hrs Follow Up (20 days) Intervention - On Study (10 days)
Transcript of PILOT RANDOMISED CONTROLLED TRIAL OF SHORT …
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PILOT RANDOMISED CONTROLLED TRIAL OF SHORT COURSE INTRAVENOUS ANTIBIOTIC THERAPY FOR ERYSIPELAS AND CELLULITIS OF THE LOWER LIMB (SWITCH TRIAL) Friedman ND1, Pollard J1,2, Walton AL1, O’Brien DP1, Cowan R1, Lim K1, Huffam S1, Lane S3, Simpson P1, Hughes AJ1, Athan E1.
Department of Infectious Diseases1, Hospital in the Home Service2, Biostatistics unit3, Barwon Health, Geelong, Victoria, Australia.
MethodsDesign: Randomized, controlled, open label, single-site pilot trial.
Target Enrolment: 40 patients.
Consecutive eligible patients were randomised by random block allocation to the intervention arm of 24 hours IV therapy or the control arm of ≥ 72 hours IV therapy (both followed by oral therapy to total duration 7-10 days).
IV antibiotics used were anti-staphylococcal penicillins and first generation cephalosporins. Oral agents included; di/flucloxacillin, cephalexin, clindamycin.
Illustration of study design:
CoNClusIoNs• This pilot randomized trial of short course therapy for cellulitis has determined that such
a trial is feasible.
• It is very common for patients to present to hospital for IV treatment of presumed cellulitis after receiving >48 hours of oral antibiotics.
• Enrolment into this trial with strict inclusion & exclusion criteria has been slow to date with less than 20% of screened patients being recruited.
• Recruitment was further marred by many conditions that are mislabelled as cellulitis.
• Among recruited trial patients to date, efficacy in both groups has been in keeping with expectations with regard to the non-inferiority design.
• No safety issues have been identified to date.
• This well-designed randomised clinical trial with strict inclusion and exclusion criteria that will lead to results of high validity.
• A single trial site will be unable to recruit the required number of participants within an acceptable timeframe.
• The SWITCH trial is expanding into a multi-centre study in Australia and Zealand in 2014.
• Participants will no longer be excluded based on receiving oral antibiotics prior to recruitment.
Photographic assessment of the affected limb at visits 1, 2, & 3:
aCKNoWledGeMeNts This project has been funded by a grant from Department of Health, Victoria.
Barwon Health Geelong, VIC, Australia
Inclusion Criteria
• Spontaneous cellulitis of lower limb with consistent clinical features, including; erythema, pain, and swelling with onset within 48 hours with either fever on clinical examination or history consistent with fevers and/or chills, rigors, nausea within 48 hours prior to presentation
• Age > 18 years
• Patient is planned for hospital admission or hospital-in-the-home IV treatment for cellulitis of the lower limb
exclusion Criteria
• Age <18 yrs or Pregnant Female
• Immunosuppression
• Alternative diagnosis, including venous eczema, Diabetic foot infection, Surgical site (wound) infection or other open wound
• Penetrating injury or bite
• Suspected complication such as abscess or necrotising infection
• Septic shock or other reasons for intensive care unit admission
• Antibiotics effective against cellulitis for > 48 hours orally or > 24 hours IV
• Patient unwilling to participate or in the opinion of investigators will be unable to comply
INtroduCtIoN & PurPoseCellulitis is a common skin and soft tissue infection with an incidence of 16.4-24.6/1000 person-years. Cellulitis and erysipelas can be differentiated according to the tissues affected; erysipelas affects the upper dermis, including the superficial lymphatics, while cellulitis involves the deeper dermis, and subcutaneous fat. The most common causative organism is Streptococcus spp. and the infections that result carry an excellent prognosis.
Although antibiotics are the mainstay of therapy for erysipelas and cellulitis, to date there is no consensus on whether intravenous or oral therapy are optimal choices, and the suggested duration of therapy. This randomized controlled non-inferiority trial was undertaken to determine the safety and efficacy of 24 hours intravenous (IV) antibiotic therapy compared to 72 hours or more of IV antibiotic therapy (both followed by oral therapy) for the treatment of cellulitis and erysipelas. Australian and New Zealand Clinical Trial Registry ANZCTR Number 365426.
We hypothesize that short-course IV therapy is not inferior to longer duration IV therapy for the treatment of cellulitis and erysipelas.
resultsOver a 12 month period from November 2012, 243 patients were screened for participation in the SWITCH trial. 40 patients were recruited to the pilot trial (16%) and 203 patients (84%) fulfilled one or more exclusion criteria.
The majority of patients were excluded based on having received oral antibiotics for >48 hours prior to presentation at our institution.
Many other patients were excluded based on an alternative diagnosis including venous eczema, diabetic foot infection and infected surgical wounds. Approximately 9% of excluded patients either decided not to participate, or were deemed to be unlikely to be able to comply with the study.
20 patients were randomized to ≥72 hours IV therapy; 19 successfully responded to therapy and 1 case withdrew prematurely.
20 patients were randomized to 24 hours IV therapy; 17 responded successfully and 3 withdrew prematurely. 1 of these patients was withdrawn because of ICU admission.
1 patient developed self-limiting, non C.difficile diarrhea after visit 3. There were no other adverse events.
A retrospective review of 12 months of cellulitis cases in 2011-2012 revealed that 59 of 265 cases of cellulitis (22%) would have met criteria for inclusion in this trial.
Primary outcome Measures:
Resolution of cellulitis, defined by the following 3 criteria:
1) Absence of progression of skin & subcutaneous abnormalities at visit 2
2) Resolution of fever at visit 2
3) Absence of ongoing requirement for antibiotic therapy beyond study period of 10 days.
secondary outcome Measures:
1) Assessment of self-reported pain using Wong-Baker face scale
2) Blinded photographic assessment of affected limb
3) Adverse events
4) Disease recurrence within 30 days
Patient Identification & Eligibility Assessment
Vist 3 (Day 7-10)
Vist 2 (Day 3-4)
Consent & Randomisation Visit 1 (Day 0)
Follow Up Phone Contact
(Day 30)
Screening - 24hrs Follow Up (20 days)Intervention - On Study (10 days)
