Use of a Single Dose of Oral Prednisone in the Treatment of Cellulitis

Study Overview
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Brief Summary
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Cellulitis is the medical term for an infection of the skin, with symptoms including redness, swelling, warmth, and pain. This group of symptoms is called inflammation, and is caused by the body's immune system responding to the infection. Standard care for cellulitis is using antibiotics to destroy the infection, but the inflammation can persist and cause a great deal of pain. The hypothesis of this study is that adding a single dose of an oral steroid (prednisone), which tempers the immune response, will reduce inflammation, reduce pain, and speed recovery. This hypothesis will be examined by recruiting a group of patients with cellulitis, and randomizing them to two sub-groups: one group will receive a dose of prednisone, while the other group will receive a placebo. Neither group will know what they received unless there is a problem. These subjects will be followed up at the 48 hour mark and the 7 day mark, and will have their results compared.

Detailed Description
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This pilot study will be conducted in a prospective, double-blinded, placebo-controlled, randomized fashion using a convenience sample of 100 subjects who come to the ED with signs and symptoms of cellulitis. Initial medical assessment will be made by an attending/senior resident according with established clinical procedures, including the history, physical examination, and vital signs. If by clinical assessment the patients meet eligibility criteria, then they will be approached by a research associate for screening, informed consent process, enrollment in the study, and data collection. After the subjects understand and sign the informed consent form, they will be randomized to either the placebo group or treatment group. The EMCP pharmacy will be in charge of the randomization process. Once randomized, a standard source document (see data management section and appendix C for details) will be filled with information given by the subjects and in their charts. While study medication is given (time zero), subjects will receive a Visual Analog Scale (VAS) to rate their pain upon initial presentation along with determination of size of the cellulitic area. This will be done by determining the longest axis of the cellulitic area and measuring it (in mm) from the most proximal/lateral end towards the most distal/medial end, excluding any lymphangitic spread. The most proximal and distal area of erythema will be outlined. While the standard treatment of care for cellulitis will be circumscribed according to already established protocols, the class of antibiotics and pain control that patients receive will depend on their disposition: If discharged: Antibiotic prescriptions will be TMP/SMX 160/800 mg (Bactrim DS), 2 pills PO BID and Cephalexin 500 mg PO qid; if allergic, Clindamycin 300 mg PO QID. Pain control: during stay in the ED subjects will receive, according to their allergic history and as long as the treating physician determines it is necessary to address the pain, two tablets of either Percocet 5/325 mg,Vicodin 5/500 mg (if allergic to Percocet), or Acetaminophen 500 mg as an only dose. Once discharged they will receive, according to their allergic history and the physician's clinical judgement, a prescription of 12 tablets of either Percocet 5/325 mg, Vicodin 5/500 mg (if allergic to Percocet), Tylenol #3 300/30 mg, or Acetaminophen 500 mg, one tablet PO q6 and PRN for pain. Pain medication must not include NSAIDs. If admitted to observation unit: antibiotics will be IV Clindamycin 300 mg q6 hours; if allergic, IV Vancomycin 1 g q12 hours should be given. For pain control: Morphine 4 mg IV q4 hours and PRN pain; if allergic, Dilaudid 1 mg IV q4 hours and PRN if pain. Pain medication must not include NSAIDs. Once discharged, they will receive the same prescription as the discharged group of subjects. In addition to the standard of care described and any additional medications deemed appropriate by the attending physician that do not represent a confounding factor to the study (NSAIDs, other antibiotics), subjects will also receive an additional pill which will be either prednisone 60 mg or placebo. If the treating physician feels it is in the best interest of the subject to break the protocol, the subject's participation in study procedures will end. Data that has already been collected will be kept, and may be analyzed separately. Once the subjects have received the study medications, they will follow their dispositions (either be discharged or be admitted in the observation's unit). To assure treatment compliance, the Research Associate will provide the subjects with antibiotics and pain medication treatment corresponding to the first 48 hours. After this landmark, the subjects will cover the rest of their treatment. Subjects will be instructed not to take any medication outside the prescription during the length of the study. If the subjects take NSAIDs during the first 48 hours, this could be considered a confounding factor. As such, subjects who take NSAIDs within the first 48 hours will have their participation in study procedures ended. Their already collected data will be kept and may be analyzed separately; however, if they take NSAIDs after the 48-hour visit their study participation will continue. Subjects will be required to return to the ED after 48 hours and bring the remaining prescribed pain medications. They will meet a Research Associate for re-evaluation, which will be done by using a VAS, measuring the cellulitic area, and assessing the degree of usage of the prescribed pain medications. This second visit is not part of the standard of care so patients won't be required to receive a formal evaluation by an ED doctor nor register in triage. Financial compensation will be provided on completion of the 48 hour follow-up visit for all patients. A seventh (± one) day follow-up call will be done to assess pain severity, degree of symptomatic recovery and disappearance of the erythema, and need of additional medical assistance.

Official Title
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Use of a Single Dose of Oral Prednisone in the Treatment of Cellulitis

Conditions
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Cellulitis

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 years Current episode of cellulitis Erythema greater than 5 centimeters in any dimension Pain, swelling, warmth, and tenderness in the area without elevated borders Dispositioned for discharge from the Emergency Department or Observation Able to consent Exclusion Criteria: Steroid use in the past 2 weeks History of adrenal insufficiency Any infection treated with antibiotics in the past 2 weeks Allergy to: Steroids Acetaminophen Trimethoprim-Sulphamethoxazole (TMP/SMX), Cephalexin, and Clindamycin (must be allergic to all three for exclusion) Oxycodone and Hydrocodone (must be allergic to both for exclusion) If subject is going to the Observation unit, allergy to: Clindamycin and Vancomycin (must be allergic to both for exclusion) Morphine and Hydromorphone (must be allergic to both for exclusion) Suspicion or presence of abscess Suspicion or presence of deep vein thrombosis Suspicion or presence of severe sepsis, as defined by: Sepsis Hypotension (systolic pressure < 90 mmHg or reduction of 40 mmHg from baseline) Failure of single end organ Suspicion or presence of septic shock, as defined by: Severe sepsis Hypotension that is refractory to fluid management Failure or more than one end organ Crepitus Change in mentation Tachycardia greater than 120 beats per minute Fever greater than or equal to 39 degrees Celsius Hospital admission Under 18 years of age, or over 70 years of age Pregnancy or breast feeding Police custody or prisoner Cognitive impairment Inability to consent Nursing home residents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prednisone<br>In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. | Drug: Prednisone<br>* See Prednisone arm description<br>* Other names: Sterapred;|
| Placebo Comparator: Placebo<br>In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. | Drug: Placebo<br>* See Placebo arm description<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale(VAS) for Pain - Day 1 to 48 Hours | The level of pain as measured by a Visual Analog Scale(VAS) measured once at day 1 and once during the 48th hour follow-up visit. Minimum value 0, maximum value 100mm, higher scores corresponds to more pain/worse outcomes. | Assessed once at day 1 and then once during the 48 hour follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Pain Medication - Day 1 to 48 Hours | Number of times the subject needed to use pain medication between day 1 and the 48 hour follow-up | Assessed once during the 48 hour follow-up | 
| Amount of Pain Medication - Day 1 to 7 Days | Total amount of pain medication used between day 1 and the 7 day follow-up call. | Assessed once during the 7 day follow-up | 
| Amount of Pain Medication - 48 Hours to 7 Days | Amount of pain medication the subject needed to use between the 48 hour follow-up and the 7 day follow-up. | Assessed at the 48 hour follow-up and at the 7 day follow-up | 
| Number of Participants Requiring Additional Medical Assistance Post-Randomization | Need for additional medical intervention to treat the current episode of cellulitis. | Assessed continuously from day 1 to the day 7 follow-up call | 
| Disposition Trend | Disposition of the subject at the end of the initial visit on day 1; Disposition Trend refers to whether the subject was discharged to home or admitted to observation unit in the hospital. This Outcome Measure intends to assess improvement from baseline following intervention. | Assessed once during day 1 | 
| Adverse Events (AE) | Development of adverse events during study period such as: allergic reaction, development of severe sepsis or septic shock, crepitus, change in mentation, fever greater than or equal to 39 degrees Celsius, tachycardia (heart rate over 120 beats per minute) | Assessed continuously from day 1 to day 7 follow-up | 
| Change in Erythema Size - Day 1 to 48 Hours | Change in erythema size - day 1 to 48 hours = (Mean erythema at Day 1) - (Mean erythema at 48 hrs) Erythema is measured in millimeters using the most proximal and distal area of the erythema. Higher values represent worse outcome. | Calculated once at 48 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cellulitis, Skin infection, Prednisone, Steroid, Anti-inflammatory