A Single Center Clinical Trial to Evaluate the Effect of Sclerotherapy on Fistulas and Sinus Tracts in Adult Patients With Hidradenitis Suppurativa
Phase: PHASE2
Conditions: Hidradenitis Suppurativa
Sponsor: Beth Israel Deaconess Medical Center

NCT Number:  
NCT02805595 
Official Title: 
Effect of Sclerotherapy on Fistulas and Sinus Tracts in Hidradenitis Suppurativa 
Document Type: 
Protocol with Statistical Analysis Plan  
Document Date: 
02/22/2019 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
A Single Center Clinical Trial to Evaluate the Effect of 
Sclerotherapy on Fistulas and Sinus Tracts in Adult Patients with 
Hidradenitis Suppurativa 
Principal Investigator 
Dr. Martina Porter 
 
 
 
B1. 
PURPOSE OF PROTOCOL 
The purpose of the protocol is to evaluate the effect of sclerotherapy on fistula and sinus tract 
evolvement using hypertonic saline injections in fistulas and sinus tracts in subjects with hidradenitis 
suppurativa 
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
Hidradenitis Suppurativa (HS) is a chronic suppurative disease characterized by firm, tender, 
inflammatory, red nodules that often evolve into fluctuant and malodorous painful abscesses, 
fistulas, and non-healing sores.  Rupture of the lesion, suppuration, formation of sinus tracts and 
scarring frequently occurs. It has been estimated to affect up to 4% of the population, affecting 
women more commonly than men. A study performed in 20071 showed that the disease can cause 
significant morbidity, especially among patients who have an early onset of disease, long duration 
and continuous evolution. Proposed etiologic factors include follicular occlusion, bacterial infection, 
genetics2-4, host defense defects, hormonal influences, cigarette smoking, and irritants. Although the 
current belief is that the primary defect is occlusion of the terminal parts of the follicular 
acroinfundibulum5 and recent genetic information supports this hypothesis,6,7  the apocrine milieu is 
likely to  play a meaningful role in the disease because it primarily affects apocrine gland-containing 
regions such as the axillary, inguinal and perineal areas. Importantly, the disease also responds well 
to complete excision of these apocrine gland-containing sites. While this approach is substantially 
disfiguring, requiring large areas of excision, it also typically results in a cure in the region excised, 
while other areas will remain active.   
In order to classify HS the Hurley classification and the Sartorius scoring system are used, both rely 
on clinical data, which may be inaccurate because of the difficulty in assessing the extensiveness of 
the lesions beneath the skin surface. This can lead to underestimation of severity.8 Ultrasound has 
also been used as a low-invasive and safe method for evaluating the lesions of HS. 
One persistent problem for many patients is the continued presence of draining fistulas and sinus 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
tracts lined with epithelium that can sometimes form “honeycomb network”. Because the tracts are 
lined with epithelium, they are unlikely to close or fill in by themselves. A treatment approach that 
has evolved to manage this persistent problem is sometimes called “unroofing” or “deroofing” in 
which the surface the epithelial track is slit and laid open. As shown in appendix 1, the disadvantage 
of this treatment is the wide area of surgical exposure and morbidity that results.   
Sclerotherapy is a well-known, safe and successful treatment for spider and varicose veins. A 
sclerosant is injected directly into the varicose vein and causes endothelial and vein wall damage, 
which leads to occlusion and ultimately results in fibrosis of the targeted vein. One of the sclerosants 
commonly used in clinical practice is hypertonic saline, which causes dehydration of endothelial cells 
and denaturation of cell surface protein and ultimately causes the vein to collapse and close. 
Hypertonic saline is one of the most popular agents because of lack of allergenicity, low cost and easy 
availability. A downside is that upon injection patients experience more pain, because of stinging, in 
comparison with other sclerosants but complication rates such as ulceration are low. Excision is the 
only reliable way to treat these semi-permanent HS lesions. The less-invasive sclerotherapy 
treatment might be an alternative for this since it can disrupt the epithelial lining and allow for 
wound healing from the inside of the tract to occur.  
We have treated two patients with this as innovative therapy using 0.2-0.4 cc of hypertonic saline 
injected in to a tract. In patient one, we did 2 treatments about 1 month apart with substantial 
reduction in the lumen of the fistula. Patient 2 has been treated once and asked for a second 
treatment.  Patient one had some erythema development near the site about 1 month after 
treatment, which resolved and appeared to be due to concomitant disease outside the treated 
fistula. Both patients, as expected, experienced mild to moderate stinging. 
 
This project was first started at MGH through cede review and are now continuing it at Beth Israel 
Deaconess Medical Center, which will be the only study site.  
 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
 Study Design and plan:  
The design of this study is a single center, single-blinded clinical research treatment study. This clinical 
study will be conducted at Beth Israel Deaconess Medical Center in Boston (the study was previously 
conducted at MGH and is currently being conducted at both institutions through Cede Review with MGH 
as the overseeing IRB and BIDMC). All subjects with a signed informed consent will be screened to 
ensure they meet all inclusion criteria and do not meet the exclusion criteria. After enrolment, the 
duration of the study is approximately 8 weeks, involving 3 or 4 visits. A schematic overview of the main 
procedures during each visit is illustrated in Appendix 2. 
 
The clinical effect of the hypertonic saline treatment will be evaluated with Physician and patients 
Assessments at week 2 (t=2), week four (t=4) and week 8 (t=8) and compared with the first visit 
(baseline) (t=0). If necessary, subjects will be eligible to receive another hypertonic saline injected in 
week 2 and/or week 4, with a maximum of three injections. Simultaneously improvement will be 
assessed by ultrasound if possible, using the Philips Lumify Ultrasound Device, and by patients using HS 
Improvement Assessments. Pain and stinging during treatment sessions will be monitored using 
numeric rating scales (NRS). For monitoring quality of life the DLQI will be used. 
 
Prior to performing any study related procedures, the investigator will discuss with each subject the 
nature of the study, its requirements and its restrictions. A written informed consent form will be 
obtained from each participant prior to any procedure. Each subject with a signed informed consent 
form will be screened at the first visit, to ensure all the inclusion criteria are met and none of the 
exclusion criteria. Medical history and demographic information will be taken. Patients will have their 
medication reviewed and undergo a full HS examination, including lesion counts, Hurley staging and 
target site assessment. Target HS area(s) will be digitally photographed and be imaged with ultrasound. 
The duration of the study is approximately 8 weeks, involving a minimum of 3 and a maximum of 4 
visits. In case of an adverse event or disease progression, patients are instructed to call and/or visit the 
clinic. An overview of the exact procedures during each visit can be found in the chart 
 
Study Table (Chart with Study Procedures) 
Activity 
(timeline)  
0 week 
(Baseline) 
2 Week 
4 Week 
Week 8 
Subject 
Information and 
Informed Consent 
 
 
 
 
Eligibility Criteria  
 
 
 
 
Medical History  
 
 
 
 
Prior and 
concomitant 
therapy  
 
 
 
 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
Review and 
document 
pregnancy 
avoidance with 
females of child 
bearing age 
 
 
 
 
23.4% Hypertonic 
Saline Injection 
 
 
 
 
Urine Pregnancy 
Test (For all 
females of 
childbearing age) 
 
 
 
 
Ultrasound (to  
locate the tracts)  
 
 
 
 
 
 
 
B. 
Statistical Considerations 
a. Sample Size Justification:   
The total number of subjects to be studied is 20 and the number to be studied at BIDMC is 14.  
A sample size calculation is not applicable, for this is an early feasibility and tolerability pilot study. 
 
b. Data Analysis:   
 
Primary study parameter(s) 
The clinical efficacy will be measured by Physician and patients Assessments. These are continuous 
variables and depending on the date distribution a one way ANOVA, a Kruskal Wallis or a Wilcoxon 
rank sum test will be performed for analysis. 
Secondary study parameter(s) 
Hence the small patient group in this pilot study, no power is expected from statistical analysis. 
Therefore all outcomes will be assessed by using descriptive statistics. 
The clinical efficacy will also be measured using the following outcomes: 
 
Measuring the length and the lumen of the fistulas using ultrasound if possible. Since this 
variable is highly dependent on investigator and experience with ultrasound, descriptive statistics will 
be used to present this variable. 
The patient reported outcomes: 
 
HS Improvement assessment: this is a continuous variable and depending on the date 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
distribution a one way ANOVA, a Kruskal Wallis or a Wilcoxon rank sum test will be performed for 
analysis. 
 
NRS to assess pain and stinging: continuous variable. Per individual a percentage 
improvement will be calculated as a main outcome.  
 
DLQI: continuous variable. this is a continuous variable and depending on the date 
distribution a one way ANOVA, a Kruskal Wallis or a Wilcoxon rank sum test will be performed for 
analysis. 
 
C. 
Subject Selection 
Patients potentially eligible for this study are at least 18 years of age and have active HS sites with 
fistula(s) or sinus tracts. A total of 20 subjects will be enrolled in the study. Potential patients will be 
assessed for eligibility to participate in this clinical study using the criteria for inclusion and exclusion 
listed below.  
Inclusion Criteria: 
A subject must meet all of the following criteria in order to be eligible to participate in this study: 
1. 
Male or female subjects are at least 18 years of age or older  
2. 
A confirmed diagnosis of HS disease 
3. 
Presence of inflammatory HS lesion(s) and one or more fistula(s) or sinus tracts 
 
Exclusion Criteria: 
Eligible subjects will be excluded from participation if they meet any of the following criteria: 
1. 
Receiving any other kind of treatment for fistulas including introduction of anti-inflammatory 
systemic therapy such as prednisone or adalimumab within the prior month. 
2. 
Are currently pregnant or planning to get pregnant during the study. 
3. 
Are participating in another study using an investigational agent or procedure during 
participation in this study.  
4. 
Have any condition that, in the opinion of the investigator, would compromise the well-being 
of the subject or the study. 
Urine Pregnancy Test 
A urine pregnancy test will be performed locally for all females of childbearing potential at the 
Baseline Visit prior to the first dose of study drug and at minimum at monthly intervals (either at 
study visits or at home between scheduled study visits). The results of the monthly at home tests 
must be communicated to the site. More frequent pregnancy tests will be performed throughout the 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
study if required per local/country requirements. 
• If the Baseline urine pregnancy test performed at the site is negative, then dosing with study 
drug may begin. 
• If the Baseline or postbaseline urine pregnancy test performed at the site is positive, dosing 
with study drug must be withheld and a serum pregnancy test is required. The serum 
pregnancy test will be performed by the central laboratory. If the serum pregnancy test is 
negative, study drug may be started or resumed. If the serum pregnancy test is positive, study 
drug must be permanently discontinued. In the event a pregnancy test comes back 
borderline, a repeat test is required (≥ 3 days later). If the repeat serum pregnancy test is: 
o Positive, the subject must be discontinued; 
o Negative, the subject can continue in the trial; 
o Still borderline ≥ 3 days later, this will be considered documentation of continued lack 
of a positive result and the subject can continue in the study (unless prohibited locally) 
in the absence of clinical suspicion of pregnancy and other pathological causes of 
borderline results. 
If time between visits is longer than 1 month, then collect the results of the monthly at home urine 
pregnancy test between scheduled visits. 
 
If during the course of the study a female becomes surgically sterile or postmenopausal and 
complete documentation as described in Protocol Section 5.2 (Contraception Requirements for 
Females) is available, pregnancy testing is no longer required. 
 
A pregnant or breastfeeding female will not be eligible to enter the study or be allowed to continue 
study drug. 
  
B4. 
POSSIBLE BENEFITS 
The potential benefits of this study are that the individual subject’s Hidradenitis Suppurativa caused 
fistulas and sinus tracts might improve with the administration of sclerosants like hypertonic saline. 
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
Hypertonic saline is as effective as other sclerosants with the advantage of lack of allergenicity and low 
costs. The most common adverse events or risks associated with sclerotherapy using hypertonic saline 
are hyperpigmentation, teleangiectic matting (neovascularization), pain, ulceration and tissue necrosis. 
Other reported less common adverse events include exacerbation of hypertension, necrosis of kidney 
cortex, hemolysis, hematuria, central nervous system disorders, hypernatremia and membranous fat 
necrosis. 
 
When used to treat fistulas or sinus tracts, none of the systemic adverse events are expected to occur. 
The common adverse events can be minimized by adhering to meticulous technique. 
 
Risks listed in ICF are as follows: 
More Common: Stinging, pain in the injected area 
Less Common: Skin Ulceration,  
Rare: Infection  
 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
Recruitment 
Dermatologists from Beth Israel Deaconess Medical Center will be informed using IRB-approved 
recruitment letters of this study and asked to refer eligible patients to our research unit. These 
letters will explain the purpose of the research, including a brief description of the nature and extent 
of involvement, and the investigator's email and phone number will be included.  A research study 
advertisement will also be posted in the dermatology clinic. 
 
A list of potential subjects will be compiled from Dr. Kimball and Dr. Porter’s patient population using 
ICD codes for HS. These identified patients will be sent recruitment letters informing them of the 
study and to contact one of the doctors if they are interested. 
 
The study will also be placed on TrialX as well as skinstudies.com, craigslist, twitter and BU quickie 
jobs. TrialX will use clinicaltrials.gov information; skinstudies.com, craigslist, twitter and BU quickie 
jobs will use the recruitment flyer and language from the targeted provider email.  
 
We will advertise the study on Twitter as well with the following posting: “Do you have Hidradenitis 
Suppurativa (HS)? You may be eligible to participate in a clinical trial. If you are interested visit our 
website skintudies.com, email us at clears@bidmc.harvard.edu or call at 617-667-5834.”  
 
Consent 
Prior to entering the study, a licensed physician investigator will explain to the potential subject the 
nature of the study, its purpose, procedures, expected duration, and the benefits and risks involved 
in study participation.  The licensed physician will explain the main study. 
 
Subjects will be given the opportunity to ask questions and be informed of their right to study 
withdrawal.  After this explanation and before any study-specific procedures have been performed, 
the potential subject may voluntarily sign and date the informed consent form for the main study, 
thereby giving permission for the subject to enter the study.  
 
Prior to participation in the study, the subject will receive a copy of the signed and dated written 
informed consent form and any other written information provided to the subject. If, for any reason, the 
subject desires more time to consider the decision, the subject will be given a copy of the unsigned 
consent form for reference and instructed to call the office if they decide to participate in the study. 
 
Subject Protection 
In order to address the issue of patients feeling pressured to participate, a standard approach was 
developed and implemented years ago. This gives the patient the opportunity to actively 
demonstrate their interest before enrolling in the study. If a discussion about the study presents 
itself during a clinical encounter, the patient is offered to take the consent home and read and then 
asked to follow up with the clinic if they are interested. It is also attempted to have a physician who 
is not involved in their clinical care go over their consent form in order to provide further separation.  
 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
B7. 
STUDY LOCATION 
 Privacy  
Subject visits will be conducted in the CRC at BIDMC or, rarely, in private patient exam rooms in the 
dermatology clinic if the CRC is not available at the time of subject visits.  Both locations should 
ensure adequate privacy for patients.  Patients will complete all study related procedures in these 
private settings, including questionnaires.  Questionnaires will be in written form and returned 
directly to the investigators or study staff. 
 
Pre-screening telephone calls and subject visits will be limited only to the minimum amount of data 
necessary to accomplish the research purposes.  No sensitive questions will be discussed by 
telephone 
 
 Physical Setting 
Subject visits will be conducted in the CRC at BIDMC or, rarely, in private patient exam rooms in the 
dermatology clinic if the CRC is not available at the time of subject visits.  Both locations should 
ensure adequate privacy for patients.  Patients will complete all study related procedures in these 
private settings, including questionnaires. 
 
 
B8. 
DATA SECURITY 
All subjects will be assigned a subject number at their screening visit.  Only investigators and study 
staff at BIDMC will have access to the subject’s identifiable health information. To ensure 
appropriate privacy and confidentiality, any paper source documentation and questionnaires will be 
stored in a locked cabinet.  Only the PI, sub-investigator, and study staff will have access to this 
locked cabinet. This documentation will all be coded.  Subject’s identifiable health information will 
be kept separate from coded documentation.  Any electronic data containing PHI will be stored on a 
password protected computer in a locked office and on a secure server behind the BIDMC firewall.  
The Investigator will maintain adequate records for the study, including resultssource 
documentation, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, adverse events, and other pertinent 
data. All essential documents will retained by the Investigators for at least 2 years in a long-term 
storage facility as arranged through the CTO. 
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?       
 Yes    
 No  
 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No  
 

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Study Description – Part B 
CCI Form:  9-2015 
                                                                                                                                                                              PI Revision Date:  2/22/19 
 
B10 
Dissemination of Research Results 
Subjects will be thanked for their participation in the study immediately following their last visit.  
Because we are not able to anticipate the final completion date of the study, which may take years, 
and because we are not primarily responsible for analyzing and publishing the data, it will not be 
feasible for investigators to provide results to individual subjects.  Subjects may contact the PI 
following their completion of the study to inquire about the final findings of the study, if available to 
the investigators, at that time. 
 
Planned dissemination of research results may include abstract presentations at dermatology 
conferences and submission of data for publication in academic journals as an original research 
article.