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

• Sponsor: Albert Einstein Healthcare Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT01671423
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 2
• Duration (Months): 37
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cellulitis	Drug: Prednisone; Drug: Placebo	N/A

Detailed Description

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:

1. 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.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Use of a Single Dose of Oral Prednisone in the Treatment of Cellulitis
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Prednisone In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit.	Drug: Prednisone; See "Prednisone" arm description; Other Names: Deltasone Prednicot Sterapred
Placebo Comparator: Placebo In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit.	Drug: Placebo; See "Placebo" arm description; Other Names: Sugar Pill Inactive Drug Control

Outcome Measures

Primary Outcome Measures

1. Visual Analog Scale(VAS) for Pain - Day 1 to 48 Hours [Assessed once at day 1 and then once during the 48 hour follow-up]

   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.

Secondary Outcome Measures

1. Amount of Pain Medication - Day 1 to 48 Hours [Assessed once during the 48 hour follow-up]

   Number of times the subject needed to use pain medication between day 1 and the 48 hour follow-up

2. Amount of Pain Medication - Day 1 to 7 Days [Assessed once during the 7 day follow-up]

   Total amount of pain medication used between day 1 and the 7 day follow-up call.

3. Amount of Pain Medication - 48 Hours to 7 Days [Assessed at the 48 hour follow-up and at the 7 day follow-up]

   Amount of pain medication the subject needed to use between the 48 hour follow-up and the 7 day follow-up.

4. Number of Participants Requiring Additional Medical Assistance Post-Randomization [Assessed continuously from day 1 to the day 7 follow-up call]

   Need for additional medical intervention to treat the current episode of cellulitis.

5. Disposition Trend [Assessed once during day 1]

   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.

6. Adverse Events (AE) [Assessed continuously from day 1 to day 7 follow-up]

   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)

7. Change in Erythema Size - Day 1 to 48 Hours [Calculated once at 48 hrs]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 to 70 years

• Current episode of cellulitis

1. Erythema greater than 5 centimeters in any dimension

2. 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:

1. Steroids

2. Acetaminophen

3. Trimethoprim-Sulphamethoxazole (TMP/SMX), Cephalexin, and Clindamycin (must be allergic to all three for exclusion)

4. Oxycodone and Hydrocodone (must be allergic to both for exclusion)

• If subject is going to the Observation unit, allergy to:

1. Clindamycin and Vancomycin (must be allergic to both for exclusion)

2. 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:

1. Sepsis

2. Hypotension (systolic pressure < 90 mmHg or reduction of 40 mmHg from baseline)

3. Failure of single end organ

• Suspicion or presence of septic shock, as defined by:

1. Severe sepsis

2. Hypotension that is refractory to fluid management

3. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141

Sponsors and Collaborators

• Albert Einstein Healthcare Network

Investigators

• Principal Investigator: Scott Goldstein, DO, Albert Einstein Healthcare Network

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bergkvist PI, Sjöbeck K. Antibiotic and prednisolone therapy of erysipelas: a randomized, double blind, placebo-controlled study. Scand J Infect Dis. 1997;29(4):377-82.
• Kiderman A, Yaphe J, Bregman J, Zemel T, Furst AL. Adjuvant prednisone therapy in pharyngitis: a randomised controlled trial from general practice. Br J Gen Pract. 2005 Mar;55(512):218-21.
• Qi D, Pulinilkunnil T, An D, Ghosh S, Abrahani A, Pospisilik JA, Brownsey R, Wambolt R, Allard M, Rodrigues B. Single-dose dexamethasone induces whole-body insulin resistance and alters both cardiac fatty acid and carbohydrate metabolism. Diabetes. 2004 Jul;53(7):1790-7.
• Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med. 1996 Apr;27(4):485-9.
• Yen MT, Yen KG. Effect of corticosteroids in the acute management of pediatric orbital cellulitis with subperiosteal abscess. Ophthalmic Plast Reconstr Surg. 2005 Sep;21(5):363-6; discussion 366-7.

• Responsible Party: Scott Goldstein, DO, Attending Physician, Albert Einstein Healthcare Network
• ClinicalTrials.gov Identifier: NCT01671423
• Other Study ID Numbers: HN 4372
• First Posted: Aug 23, 2012
• Last Update Posted: Feb 10, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Scott Goldstein, DO, Attending Physician, Albert Einstein Healthcare Network: Cellulitis; Skin infection; Prednisone; Steroid; Anti-inflammatory
• Additional relevant MeSH terms: Cellulitis; Prednisone

Study Results

Participant Flow

Pre-assignment Detail	42 participants agreed to participate in the study. Following completion of informed consent process, 1 participant withdrew of their own volition, 1 participant was excluded from analysis for taking NSAID within the first 48 hrs.

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Period Title: Overall Study
STARTED	20	20
COMPLETED	14	9
NOT COMPLETED	6	11

Baseline Characteristics

Arm/Group Title	Prednisone	Placebo	Total
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description	Total of all reporting groups
Overall Participants	14	11	25
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	40	40	40
Sex: Female, Male (Count of Participants)
Female	5 35.7%	6 54.5%	11 44%
Male	9 64.3%	5 45.5%	14 56%

Outcome Measures

1. Primary Outcome

Title	Visual Analog Scale(VAS) for Pain - Day 1 to 48 Hours
Description	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.
Time Frame	Assessed once at day 1 and then once during the 48 hour follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	14	11
VAS at Day 1	79.64 (14.89)	56.45 (30.25)
VAS at 48 hrs	39.71 (34.5)	25.91 (33.25)

2. Secondary Outcome

Title	Amount of Pain Medication - Day 1 to 48 Hours
Description	Number of times the subject needed to use pain medication between day 1 and the 48 hour follow-up
Time Frame	Assessed once during the 48 hour follow-up

Outcome Measure Data

Analysis Population Description

Data is not available on all participants

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	14	11
Median (Full Range) [medications taken]	7	2

3. Secondary Outcome

Title	Amount of Pain Medication - Day 1 to 7 Days
Description	Total amount of pain medication used between day 1 and the 7 day follow-up call.
Time Frame	Assessed once during the 7 day follow-up

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	0	0

4. Secondary Outcome

Title	Amount of Pain Medication - 48 Hours to 7 Days
Description	Amount of pain medication the subject needed to use between the 48 hour follow-up and the 7 day follow-up.
Time Frame	Assessed at the 48 hour follow-up and at the 7 day follow-up

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	0	0

5. Secondary Outcome

Title	Number of Participants Requiring Additional Medical Assistance Post-Randomization
Description	Need for additional medical intervention to treat the current episode of cellulitis.
Time Frame	Assessed continuously from day 1 to the day 7 follow-up call

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	0	0

6. Secondary Outcome

Title	Disposition Trend
Description	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.
Time Frame	Assessed once during day 1

Outcome Measure Data

Analysis Population Description

Data is not available on all participants

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	14	11
Discharged to Home	12 85.7%	8 72.7%
Data not available/not collected	2 14.3%	3 27.3%

7. Secondary Outcome

Title	Adverse Events (AE)
Description	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)
Time Frame	Assessed continuously from day 1 to day 7 follow-up

Outcome Measure Data

Analysis Population Description

Data not collected on this outcome measure

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	0	0

8. Secondary Outcome

Title	Change in Erythema Size - Day 1 to 48 Hours
Description	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.
Time Frame	Calculated once at 48 hrs

Outcome Measure Data

Analysis Population Description

Data not collected on this outcome measure

Arm/Group Title	Prednisone	Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description	In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events collected upto 7 day follow up.
Arm/Group Title	Prednisone		Placebo
Arm/Group Description	In addition to standard care for cellulitis, subject will receive a single 60 mg dose of Prednisone orally during their initial visit. Prednisone: See "Prednisone" arm description		In addition to standard care for cellulitis, subjects will receive a single placebo pill to take during their initial visit. Placebo: See "Placebo" arm description
All Cause Mortality
	Prednisone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Prednisone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Prednisone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

Small sample size

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.