Clinical trial NCT02781818
Conditions: Hidradenitis Suppurativa
Keywords: hidradenitis intralesional triamcinolone
Sponsor: University of North Carolina, Chapel Hill
Start date: 2016-06-01; Completion date: 2017-07-01
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Purpose: To evaluate the effectiveness of intralesional triamcinolone for the treatment of hidradenitis suppurativa (HS)

Participants: Patients diagnosed with Hidradenitis Suppurativa that have active inflammatory HS lesions. Up to 60 lesions will be treated. Between 20 and 60 patients will be enrolled dependent on the number of lesions they have treated. (up to 3 per patient)

Procedures (methods): Injection of triamcinolone or placebo into active lesions of hidradenitis suppurativa

Detailed description:
This will be a randomized, double-blind, placebo-controlled trial of two concentrations of intralesional triamcinolone, triamcinolone 40mg/mL and triamcinolone 10mg/mL, with normal saline as a placebo control. For subjects with lesions deemed appropriate for the study, between one and three treatment sites will be marked with sequential lettering with a skin marker and documented by body location. Baseline pain level of each lesion will be recorded. At that time each lesion will be randomized in a 1:1:1 fashion to be treated with intralesional triamcinolone 10mg/mL, triamcinolone 40mg/mL, or normal saline placebo.

Following treatment, subjects will be given a paper questionnaire that will ask them to rate their level of pain on a 1-10 scale for each lesion, and whether they believe the target lesion has resolved on days 1, 2, 3, 5, 7, 10, and 14. On day 14 they will also rate how helpful they think the treatment is on a scale of 0-4. These will be patient-reported outcomes only without any physician assessment as this is felt to be a more clinically relevant outcome.

Aim 1. Characterize and compare the 3 regimens in terms of days to resolution of treated lesion.

Hypotheses for Aim 1: Days to resolution of treated lesions will be fewer in the treatment groups compared to normal saline placebo, and will be fewer with triamcinolone 40mg/mL compared to triamcinolone 10mg/mL.

Aim 2. Characterize and compare the 3 regimens in terms of pain level on day 5.

Hypotheses for Aim 2: Rating of pain will be less in the treatment groups compared to normal saline placebo, and will be less with triamcinolone 40mg/mL compared to triamcinolone 10mg/mL at day 5.

Aim 3. Characterize and compare the 3 regimens in terms of patient rating of the "benefit of the treatment Hypotheses for Aim 1: Patient rating will be more favorable the treatment groups compared to normal saline placebo, and will be more favorable with triamcinolone 40mg/mL compared to triamcinolone 10mg/mL.

Arms: arm 1: Each lesion randomized to this group will receive a single intralesional treatment with 0.1 mL of triamcinolone 10mg/mL solution. arm 2: Each lesion randomized to this group will receive a single intralesional treatment with 0.1 mL of triamcinolone 40mg/mL solution. arm 3: Each lesion randomized to this group will receive a single intralesional treatment with 0.1 mL of sterile normal saline solution.
Interventions: intervention 1: Triamcinolone Acetonide 10mg/mL intervention 2: Triamcinolone Acetonide 40mg/mL intervention 3: Normal Saline
Intervention descriptions: intervention 1: Triamcinolone acetonide is a glucocorticoid used in intralesional treatment of many skin diseases, intra-articular treatment of inflammatory joint diseases, and intramuscular treatment for systemic management of systemic inflammatory diseases. It is commonly used in clinical practice for the treatment of acute abscesses and nodules of hidradenitis suppurativa, but little clinical trial data exist supporting its use. intervention 2: Triamcinolone acetonide is a glucocorticoid used in intralesional treatment of many skin diseases, intra-articular treatment of inflammatory joint diseases, and intramuscular treatment for systemic management of systemic inflammatory diseases. It is commonly used in clinical practice for the treatment of acute abscesses and nodules of hidradenitis suppurativa, but little clinical trial data exist supporting its use. intervention 3: Normal saline 0.1 mL will be administered intralesionally at the selected site.

Protocol documents:
Prot_000.pdf: 
 
A randomized, controlled, double blind study to evaluate the efficacy 
of intralesional triamcinolone in the treatment of hidradenitis 
suppurativa 
 
STUDY PROTOCOL 
 
NCT number NCT02781818 
Document Date 11/30/2017 
 


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dŝƚůĞ͗A randomized, controlled, double blind study to evaluate the efficacy of intralesional 
triamcinolone in the treatment of hidradenitis suppurativa. 
 
Purpose: To evaluate the effectiveness of intralesional triamcinolone for the treatment of 
hidradenitis suppurativa 
 
Participants: Patients diagnosed with Hidradenitis Suppurativa that have active inflammatory HS 
lesions. Up to 60 lesions will be treated. Between 20 and 60 patients will be enrolled dependent 
on the number of lesions they have treated. (up to 3 per patient) 
 
Procedures (methods): Injection of triamcinolone or placebo into active lesions of hidradenitis 
suppurativa. 
 
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Three criteria must be present for the diagnosis of HS. Firstly, characteristic lesions must be 
present, often beginning as ³blind boils´ that transition to abscesses, bridged scars, draining 
sinus, and post-inflammatory ³tombstone double-ended pseudocomedones.´1 These lesions must 
be present in the typical areas: the groin, axillae, buttocks, perineal region, and infra- and 
intermammary folds.1 The final criterion is that there must be a history of recurrence. The 
disease is typically chronic with relentless progression that frequently results in significant 
disability and quality of life impairment. 
 
The acute, painful lesions have been reported to have an average duration of 6.9 days, but 
permanent painful boils are present in 62% of patients.2 Patients develop a median of two lesions 
per month and average age of onset is 21.9 years.2 Rupture of lesions can lead to worsening 
pain, suppurativa discharge, and malodor.3  The current prevalence of HS has been reported to 
range from 0.05% to 4%, with the number of patients diagnosed substantially increasing in 
recent years.4 The rise in diagnoses is due to either increased knowledge of HS, increased ability 
to identify the clinical signs, or a true increase based on lifestyle modifications. 4 
 
A dermatologist or healthcare professional with HS experience should make the diagnosis and 
determine the clinical stage. Hurley staging is a quick way to characterize staging of the 
condition and identify appropriate therapy and likely success of treatment. We will identify the 
Hurley staging for the involved sites during the study, as this may be helpful in characterizing 
our population. 
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The exact pathogenesis of HS remains unclear, but the hair follicle is most likely the location 
where the lesion originates. Recent investigations demonstrated that the interleukin-
12/interleukin-23/Th17 pathway and tumor necrosis factor Į are involved in HS, indicating that 
the pathogenesis is immune and inflammatory related.5, 6 Intralesional steroid injections are 
commonly used for localized inflammatory skin diseases, such as cutaneous lupus 
erythematosus, cystic acne, and sarcoidosis, so it seems appropriate that intralesional 


triamcinolone will be beneficial for HS.7 HS may also be associated with comorbid diseases 
such as obesity, arthritis, anemia, lymphedema, and metabolic syndrome.8 These conditions 
should be addressed and appropriately managed by health care providers. 
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HS is primarily treated with antibiotics, biologics, and surgery in severe cases. First line 
therapies are clindamycin lotion 1%, Tetracycline, Clindamycin/Rifampicin, and Adalimumab.9 
Intralesional triamcinolone, the focus of our research study, is a common and routine treatment 
for acutely flaring HS lesions. 
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HS has a greater negative impact on quality of life than other more commonly known 
dermatologic conditions such as psoriasis, atopic dermatitis, acne vulgaris, and chronic 
urticaria.10 This is primarily due to the severe pain, discomfort, pruritus, and malodor associated 
with HS. Patients also often have an impaired sexual health, suffer from depression, and have a 
difficulty performing work responsibilities.11 Out of employed HS patients, 58.1% report work 
absence due to the condition with a mean absence from work duration of 33.6 ± 26.1 days 
annually.10 Improving clinical outcomes, such as shortened outbreaks and diminished pain, 
could have a profound effect on patients¶ professional endeavors and quality of life. 
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Despite HS being a relatively common disease that is chronic, painful, and debilitating, it has 
still not received much research or societal attention. To date, limited clinical trial data exists 
supporting treatment of HS and the management of acute exacerbations. Clinical experience 
suggests that intralesional triamcinolone may be useful, but its effectiveness has not been 
extensively assessed. Intralesional triamcinolone injections are commonly used for localized 
inflammatory skin diseases, so it will likely benefit HS patients as well.7 
 
Our proposed study seeks to answer two of the top 10 uncertainties set by The Hidradenitis 
Suppurativa Priority Setting Partnership: ³What is the best management of an acute flare?´ and 
³What is the best management of pain associated with HS?´5 Analyzing the efficacy of 
intralesional triamcinolone at resolving lesions and decreasing pain could help guide 
dermatologists¶ treatment of HS and provide better outcomes for patients. Patients with HS at 
UNC¶s Dermatology and Skin Cancer Centers will receive varying concentrations of 
intralesional triamcinolone or a normal saline placebo and their self-reported outcomes will be 
analyzed. 
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1. Hessel H. van der Zee, Gregor B.E. Jemec, New insights into the diagnosis of hidradenitis 
suppurativa: Clinical presentations and phenotypes, Journal of the American Academy of 
Dermatology, Volume 73, Issue 5, Supplement 1, November 2015, Pages S23-S26, ISSN 
0190-9622, http://dx.doi.org/10.1016/j.jaad.2015.07.047. 
(http://www.sciencedirect.com/science/article/pii/S0190962215019957) 
2. Von Der Werth, J. and Williams, H. (2000), The natural history of hidradenitis suppurativa. 
Journal of the European Academy of Dermatology and Venereology, 14: 389±392. 
doi:10.1046/j.1468-3083.2000.00087.x 


3. Ring, H.C., Theut Riis, P., Miller, I.M., Saunte, D.M. and Jemec, G.B. (2016), Self-reported 
pain management in hidradenitis suppurativa. Br J Dermatol. doi:10.1111/bjd.14266 
4. Alavi, A., Cohen, A. D., Gulliver, W., Brassard, A., Danby, W. B. and Zouboulis, C. C. 
(2016), Proceedings of the Joint CHSF/HSF/EHSF pre-WCD Hidradenitis Suppurativa 
Symposium. Exp Dermatol, 25: 1±5. doi:10.1111/exd.12903 
5. Matusiak L, Bieniek A, Szepietowski J. Increased serum tumour necrosis factor alpha in 
hidradenitis suppurativa patients: is there a basis for treatment with anti-tumour necrosis factor 
alpha agents? Acta Dermatol Venereol. 2009; 89: 601±3.  
6. Schlapbach C, Hanni T, Yawalkar N, Hunger RE Expression of the IL-23/Th17 pathway in 
lesions of hidradenitis suppurativa. J Am Acad Dermatol 2011;65:790-798 
7. Verbov J (1976) The place of intralesional steroid therapy in dermatology. %ULWLVK-RXUQDORI
'HUPDWRORJ\94, (Suppl 12),51 
8. Fimmel S, Zouboulis CC. Comorbidities of hidradenitis suppurativa (acne inversa). 
'HUPDWRHQGRFULQRORJ\. 2010;2(1):9-16. doi:10.4161/derm.2.1.12490. 
9. Gulliver W, Zouboulis CC, Prens E, Jemec GB, Tzellos T. Evidence-based approach to the 
treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for 
hidradenitis suppurativa. Reviews in endocrine & metabolic disorders. 2016.  
10.Matusiak , Bieniek A, Szepietowski JC. J Am Acad Dermatol. 2010 Apr;62(4):706-8, 708.e1. 
11. Deckers, Inge Elizabeth, MD; Kimball, Alexa Boer, MD, MPH. Published January 1, 2016. 
Volume 34, Issue 1. Pages 17-22. © 2016. 
 
Study Aims: 
Aim 1. Characterize and compare the 3 regimens in terms of days to resolution of treated lesion. 
Hypotheses for Aim 1: Days to resolution of treated lesions will be fewer in the treatment groups 
compared to normal saline placebo, and will be fewer with triamcinolone 40mg/ml compared to 
triamcinolone 10mg/ml. 
 
Aim 2. Characterize and compare the 3 regimens in terms of pain level on day 5. 
Hypotheses for Aim 2: Rating of pain will be less in the treatment groups compared to normal 
saline placebo, and will be less with triamcinolone 40mg/ml compared to triamcinolone 10mg/ml 
at day 5. 
 
Aim 3. Characterize and compare the 3 regimens in terms of patient rating of the ³benefit of the 
Treatment Hypotheses for Aim 1: Patient rating will be more favorable the treatment groups 
compared to normal saline placebo, and will be more favorable with triamcinolone 40mg/ml 
compared to triamcinolone 10mg/ml. 
 
Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Male and females > or = 16 years of age 
2. Diagnosis or history of clinical features consistent with hidradenitis suppurativa for >1 year 
3. Patient must have an inflammatory lesion at the time of treatment. This can be an 
inflammatory nodule defined by a tender, palpable subcutaneous nodule, or an abscess defined as 
as fluctuant, painful, subcutaneous nodule. Lesions greater than 2 centimeters in size will not be 
excluded. Inflammatory nodules or abscesses can be treated if they are associated with a sinus 
tract, which is a 


chronic HS lesion defined by tunneled lesion with multiple openings to the surface of the skin. 
Sinus tracts without associated nodules or abscesses will not be treatment targets. 
4. Patient must be off of antibiotics or on a stable course of oral antibiotics for >4 weeks prior to 
the baseline visit. Allowable antibiotics during treatment course are topical clindamycin, topical 
chlorhexidine gluconate, oral doxycycline, oral minocycline, or oral clindamycin +/- rifampin. 
5. Must be able to provide adequate informed consent for themselves 
 
Exclusion Criteria: 
1. Any patient with signs of active infection at the time of screening that is not related to their 
hidradenitis suppurativa. 
2. Patients who have been on non-permitted antibiotics in the 4 weeks prior to baseline. 
Allowable antibiotics during treatment course are topical clindamycin, topical chlorhexidine 
gluconate, oral doxycycline, oral minocycline, or oral clindamycin +/- rifampin. 
3. Patients who have had surgical intervention of the treated body region (i.e., right axilla) 
beyond incision and drainage procedures in the last 8 weeks or with open surgical wounds in the 
treatment region. 
4. Patients who have been started on immunomodulatory or biologic treatment (i.e., adalimumab, 
infliximab) in the past 4 weeks 
5. Patients on non-stable doses of opiate analgesics for the last 14 days prior to screening 
6. Patients with history of hypersensitivity reactions to triamcinolone 
7. Ongoing health or physical exam concerns which the investigator feels may put the patient at 
significant risk 
 
Study Design 
This will be a randomized, double-blind, placebo-controlled trial of two concentrations of 
intralesional triamcinolone, triamcinolone 40mg/ml and triamcinolone 10mg/ml, with normal 
saline as a placebo control. Target enrollment is up to 60 lesions with 1-3 lesions treated in each 
patient enrolled.  Screening will be performed during regularly scheduled clinic visits with the 
principal investigator (C.S.). Informed consent will be signed by the subject. Physical exam will 
be performed to assure that inflammatory lesions suitable for treatment are present. Once 
subjects are deemed appropriate for the study, between one and three treatment sites will be 
marked with sequential lettering with a skin marker and documented by body location. Pain level 
of each lesion will be recorded. At that time the triamcinolone and/or placebo will be prepared 
by the co-investigator the drug will be concealed with opaque tape on the syringe. The principal 
investigator and subject will thus be blinded as the principal investigator administers the 
treatment.  
 
Following treatment, subjects will be given a paper questionnaire that will ask them to rate their 
level of pain on a 1-10 scale, the effectiveness of the treatment, and whether they believe the 
target lesions has resolved. They will record these scores on days 1, 2, 3, 5, 7, 10, and 14. These 
will be patient-reported outcomes only without any physician assessment as this is felt to be a 
more clinically relevant outcome. The principal investigator or co-investigator will contact 
subjects by phone to ensure that logs recording pain and days to resolution are completed in a 
timely and correct manner, but no data will be collected during the 14-day period in which 
questionnaires are completed to avoid influencing subject responses at the time of contact. After 
the final questionnaire is completed (more than 14 days after the intervention is performed), the 


co-investigator or principal investigator will contact the subject by phone to remind the subject to 
mail in their questionnaires and may allow the option to collect the data that the subject has 
already recorded. At this time, the principal or co-investigator may also ascertain if any 
previously unreported adverse events occurred during the study period. The days to resolution 
reported and pain data will be used to compare the effects of varying concentrations of 
intralesional triamcinolone with normal saline. 
 
Protocol summary: 
Day 0: Subject recruited and pre-screened, 
-Adult subjects will sign adult consent form and HIPAA authorization 
-Subjects aged 16-17 will sign the age 15-17 assent form and parents will sign the parental 
consent form. HIPAA authorization will be signed. 
-History of disease and medications will be taken 
-Physical exam will be performed to see if appropriate target lesions are present 
-Each lesion will be randomized to a treatment group 
-Treatment will be administered via intralesional injection by the principal investigator 
-Follow-up paper and pencil questionnaire will be dispensed along with a stamped and addressed 
return envelope. 
 
Day 1, 2, 3, 5, 7, and 10: 
-subject will complete corresponding section of the paper and pencil questionnaire on each of 
these days to report pain level of each lesion treated and whether each lesion has resolved. 
-between day 2-7 the subject will be contacted by phone and reminded to complete their 
questionnaires. No data will be gathered at this time. 
 
Day 14: subject will complete corresponding section of the paper and pencil questionnaire on 
each of these days to report pain level of each lesion treated and whether each lesion has 
resolved.  He/she will also answer a question regarding how they view the efficacy of the 
treatment for each location 
 
Day 14-21: 
-investigator or co-investigator will contact the subject by phone to remind the subject to mail 
the completed questionnaire or allow the option collect the data on pain, lesion resolution, and 
efficacy that was previously recorded during the study period over the phone. At that time, the 
primary or co-investigator may ascertain if any adverse effects have occurred that have not 
already been reported. 

SAP_001.pdf: 
 
A randomized, controlled, double blind study to evaluate the efficacy 
of intralesional triamcinolone in the treatment of hidradenitis 
suppurativa 
 
STATISTICAL ANALYSIS PLAN 
 
NCT number NCT02781818 
Document Date 05/17/2017 
 


Date 5-17-2017 
Statistical approach for IRB 16-0773, A randomized, controlled, double-blind study 
to evaluate the efficacy of intralesional triamcinolone in the treatment of 
hidradenitis suppurativa. 
The calculations for power justification are outlined below demonstrating 80% 
power to demonstrate our primary aim. The power to tell a difference between 
our 2 treatment groups is only 28%, but this is acceptable as a secondary aim. In 
our final analysis we will use a mixed effects regression model to account for the 
variation in number of lesions evaluated in each patient. This will account for 
some correlation among lesions treated within the same patient due to how 
patient reported lesion clearance may be somewhat effected by individual patient 
perception. 95% confidence intervals will be created for each group and p-values 
for comparisons between each group will be calculated in the final analysis for 
each study end point. 
Our secondary aim of finding differences in pain scores are appropriately 
powered with power nearing 100%. 
For our third aim demonstrating improved perception of treatment, the analysis is 
more straightforward as data is gathered at only one time point. We will perform 
descriptive analysis and report the average ratings and the corresponding 
confidence intervals. 
Simulation settings for power analysis 
There are 30 patients in which 12 have 1 lesion, 6 have 2 lesions and 12 have 3 
lesions. Each lesion is then randomized to one of 3 treatment groups (say, A, B, C) 
with equal chance. For patient k, lesion j, let T be the treatment assigned. We 
generate data as following: 
Ykj =Pi I(Tkj =A)+ P2 I(Tkj = B) + P3I (Tkj = C) +bk + ekj 
bk is a patient-specific random effect, ekj is a random error. 


We consider two scenarios, where the first one corresponds to the outcome of 
days to resolution, and the second one is for the pain scores. 
Scenario 1: 
/31 = 6,/J2 = 8,/J3 = 10; 
bk is patient-specific random effect from normal with mean 0 and standard 
deviation S-v"02; 
ekj is random error from normal with mean 0 and standard deviation sv'Q.8. 
Scenario 2: 
/31 = 2,/J2 = 4,/J3 = 6; 
bk is patient-specific random effect from normal with mean 0 and standard 
deviation .../Oi; 
ekj is random error from normal with mean O and standard deviation v'D.8. 
After simulating the data 100 times, we fit the same model, and perform two 
tests as follows: 
a. Test Pi;P
2 < /J3, report the probability of rejecting the null (one side p-
value<0.05), report the standard error of the estimates for Pi ;(J2 -
{J3 • 
b. Test /31 < {32, report the probability of rejecting the null {one side p-
value<0.05), report the standard error of the estimates for {31 - /J2 • 
The results are given in the following table. It shows that for the primary outcome 
(days to resolution}, there is 80% power to test that the combined treatment 
groups have less number of the days than the control group. The power to detect 
the difference between two treatment groups is 28%. For the secondary 
outcome of the pain scores, these numbers become 100%. 
The average 95% confidence interval for the difference between the combined 
treatment groups and the control group is (2.6, 5.6) for days to resolution and 
(2.46, 3.52) for pain scores. 
Results of the two scenarios 
Compare combined treatments vs control 
Compare two treatment groups 
Scenario 
P1+P2 _ p
3 
SE 
power 
P1 - /12 
Std err (estimates) 
power 
2 
True value 
True value 


1: days to resolution 
-3 
1.331 
0.8 
-2 
1.540 
2: pain scores 
-3 
0.266 
1 
-2 
0.300 
Final analysis of data: 
For each aim we will calculate means with 95% confidence intervals and p-values for 
comparisons between each treatment group and the placebo group. The treatment groups will 
also be combined for comparison to the placebo group. 
0.28 
1