Prospective Randomized Clinical Trial Comparing Outcomes of Secondary Intention Wound Care Methods
Phase: NA
Conditions: Wound Surgical, Wound Heal
Sponsor: Lahey Clinic

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
1 
 
LCID: 20193001  
Version #2  
22Mar2019 
 
 
 
 
 
 
Research Protocol 
 
 
 
Principal Investigator: Jeffrey Tiger, MD 
 
Sub-Investigators: Kristina Liu, MD (Prior Harvard Dermatology Resident; Currently Faculty at 
Brigham & Women’s Hospital); Ganary Dabiri, MD PhD (Roger Williams Medical Center in Providence, 
RI) 
 
 
Research Objectives / Specific Aims / Outcome Measures:  
 
Objective: 
 
To determine if debridement improves healing time for secondary intention wounds. 
 
Hypothesis 
Aggressive and frequent debridement of an acute post-surgical wound 
shortens healing time. 
 
Outcomes Measures 
The primary outcome measure will be time to healing.  
                                                    Secondary outcomes will include patient satisfaction with their scar (as 
assessed by the Patient Scar Assessment Questionnaire) at time of 
complete healing, cosmetic appearance (Visual analog Scale) as rated by a 
blinded reviewer at time of complete healing, number of required 
debridements by time of complete healing, treatment failures at week 16, 
and number of complications (including pain, bleeding, infection, tumor 
recurrence) by time of complete healing or by week 16.  
 
 
The Patient Scar Assessment Questionnaire is a validated questionnaire 
used standardly in Dermatology for assessing patient-based outcome 
measures of scarring. It consists of 5 subscales: appearance, symptoms 
consciousness, satisfaction with appearance and satisfaction with 
symptoms.  Each subscale consists of a set of items with 4-point categorical 
responses, scoring 1 to 4 points (with 1 point assigned to the most favorable 
category and 4 assigned to the least favorable). It has been demonstrated to 
be a reliable and valid measure of patients’ perception of scarring12.  
  
 
The Visual Analog Scale is a validated image-based scale that is frequently 
used in the Dermatology and Plastic Surgery literature, that uses 

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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photographs for evaluation in 5 dimensions (pigmentation, vascularity, 
acceptability, observer comfort, and contour).  “Observer comfort” measures 
the observer’s “comfort level” when viewing the wound.  The benefit of using 
this scale for the purposes of the study is because it is a photograph-based 
scale which can be evaluated later by a blinded physician rather than in the 
clinic at the time of the visit.  The observer places a mark along the 
continuum and then that is measured from left to right and a corresponding 
score is given.  The individual scores are tallied to obtain a single overall 
score ranging from “poor” to “excellent.”  It has been shown to have high 
observer reliability and internal consistency when evaluated by experts13.   
 
Background Information / Significance / Scientific Rationale:  
Secondary intention is an established method of allowing post-surgical defects to heal. Previous studies 
have shown a positive association between the frequency of debridement 
and healing rates in chronic wounds, based on the belief that debridement 
initiates the first stage of wound healing, and transforms chronic wounds 
into acute wounds. 1-4  However, the effect of debridement on acute, post-
surgical wounds is not well-described in the literature. 
 
5 One retrospective review of debridement and time to heal did include the analysis of surgical wounds and 
concluded that frequent debridement led to shorter healing times, but no 
prospective studies have been done investigating whether this subset of 
wounds show a propensity to heal without frequent and aggressive 
debridement.6 Frequent debridement may unnecessarily strip the wound of 
macrophages, fibroblasts and keratinocytes that are valuable to wound 
healing in the acute, post-surgical wound. Additionally, while it is known that 
fibrin mediates many processes related to wound healing, it is not clear 
whether the presence of fibrin impedes or facilitates healing of the acute, 
post-surgical wound. Chronic wounds and wound care represent a major 
health burden in this country with significant associated costs.4  Through this 
study, we hope to assess whether frequent debridement facilitates or 
impedes acute wound healing. Lastly, findings of this study may have 
implications on the number and frequency of follow-up clinical visit for 
patients, with direct effects on costs on the healthcare system, opportunity 
costs to the patient, as well as the availability of those appointments for 
other uses. Optimizing wound care methods in this era of accountable care 
organizations (ACO) therefore targets the triple aim of improving patient 
satisfaction, improving quality of care, and reducing overall system costs.7  

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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Participant Selection / Eligibility:  
 
Subjects 
 
1) Dermatology patients at Lahey Clinic  
2) who have undergone Mohs surgery or excision 
3) who are older than 18 years 
4) who are able to give consent 
5) who had postoperative defects allowed to heal by secondary intention on 
the a) head and neck, b) trunk and upper extremities, c) lower extremities 
6) who are willing and able to return to clinic in Peabody for all wound care 
visits 
 
Exclusion Criteria 
 
1) Unable to consent (due to language barrier, mental status) 
 
 
 
 
2) Unable to perform daily wound care 
 
 
 
 
3) Unwilling or unable to return for follow-up 
 
 
 
 
4) Have baseline venous stasis or pitting edema of the affected limb 
5) Wear compression stockings or require use of a compressive bandage  
(such as an Unna Boot) at baseline. 
 
Subject Enrollment: / Consent Process / Screening / Randomization:  
 
Randomization  
Block randomization using randomly-permuted block sizes of four and six 
will be used to ensure balanced enrollment in each arm as the trial 
progresses. Randomization will also be stratified by anatomic region.  The 
three anatomic regions include: head and neck (5 per arm), trunk and upper 
extremity (5 per arm), and lower extremity (10 per arm).  Randomization 
sequences will be generated in advance using an available web service and 
the list will be maintained by a research nurse not involved in patient 
enrollment. (Sealed Envelope Ltd. 2015. Create a blocked randomization 
list. [Online] Available from: https://www.sealedenvelope.com/simple-
randomiser/v1/lists  [Accessed 12 Oct 2015].)  Treatment allocation 
assignment for each patient will be kept in sealed envelopes by the research 
nurse until after the patient is enrolled in the study.  As patients are being 
enrolled, the clinician enrolling the patient will contact this research nurse to 
obtain the treatment assignment and will not have a priori knowledge of the 
randomization of the patient.  In order to ensure a manageable caseload, 
only 10 patients will be enrolled in the study at any one time.  Once 10 

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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people are enrolled, then enrollment will stop until a patient completes the 
study, at which point randomized enrollment will resume.   
   
 
 
Study Design / Procedures:  
Randomized Clinical Trial 
 
Enrollment 
At the baseline visit, after the patient has signed consent and been randomized to 
their specific treatment arm, we will obtain basic demographic information including 
age, sex and race, as well as pertinent comorbidities that would affect wound 
healing such as diabetes, venous stasis, immunosuppression and tobacco use (if 
documented as problems in the patient’s chart). Wound defect width, length, and 
depth will also be measured at baseline, prior to any intervention.  
 Intervention Arms: 
1) Aggressive debridement: Aggressive and frequent debridement of fibrin and crust 
from the wound base down to pinpoint bleeding, both by the patient as part of daily 
wound care at home, and also by the clinician (either physician or experienced 
dermatologic surgery nurse) during follow-up visits. Silver nitrate will be used to treat 
excessive granulation tissue only if the granulation tissue is higher than the level of 
surrounding skin.  Patients will return weekly until healed.  Patients will be provided 
with detailed instructions and guidelines to help determine whether healing has 
taken place. 
 
 
2) Minimal debridement: No debridement of fibrin by the patient or the clinician. 
Exceptions include debridement of dried crust or eschar. Silver nitrate will be used to 
treat excessive granulation tissue only if the granulation tissue is higher than the 
level of surrounding skin. Patients will return every two weeks until healed. In 
between visits at weekly intervals, the patient will be contacted by phone to 
determine if healing has occurred in between clinic visits11. Patients will be provided 
with detailed instructions and guidelines to help determine whether healing has 
taken place. 
 
Notes:  
• 
The following information will be recorded for each patient at each clinic visit for both 
treatment arms, using a standardized data collection form: Date of follow up; pain 
(0/10); episodes of bleeding (# and whether mild, moderate, or severe); amount of 
crust (mild, moderate, or severe); amount of fibrin (mild, moderate, or severe); size 

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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of wound (width, length, and depth); whether the wound is completely healed 
(completely re-epithelialized); any tumor recurrence (as determined by physician); if 
excess granulation tissue is present (as determined by being higher than the level of 
the surrounding skin); if there is infection (as determined by the physician); whether 
culture was taken; and degree of debridement (none, mild, moderate, or severe). 
• 
At each visit, we will review the treatment method with the patient (i.e. whether aggressive or 
minimal debridement), reinforce the instructions, and give them another written copy 
of their wound care methods) 
• 
We will measure time to 50% healing of the wound for all patients. 
• 
Both intervention arms (aggressive debridement and minimal debridement) are accepted 
methods of post-operative care for secondary intention wounds.  While both 
methods are practiced at Lahey Clinic, there is no known, published “standard-of-
care” in the literature for such wounds.  This is because there have been no 
randomized controlled trials undertaken comparing efficacy of these two methods.  
That is the purpose of this study. 
• 
It is the standard of care to have patients with wounds healing by secondary intention return 
to clinic for wound checks until the wounds is sufficiently healed; however, the exact 
interval period is up to the discretion of the provider.  In this study, we will be 
following up weekly with patients receiving frequent debridement and biweekly with 
patients receiving minimal debridement.  All patients will continue to be followed until 
their wounds are healed.   
 
Ongoing Care: The patient will return to clinic for evaluation until defect is completely healed, as determined 
by the principal investigator.  
 
The follow-up intervals are as noted above. 
● 
 Patients will be asked to record the date on which their wound healed, and this will be reviewed over 
the phone or at their next clinic appointment.  
 
● 
Once the wound is determined to be completely healed (full re-epithelialization), the patient will be 
asked to complete the Patient Scar Assessment Questionnaire. The Patient Scar Assessment 
Questionnaire is a validated questionnaire used standardly in Dermatology for assessing patient-
based outcome measures of scarring. It consists of 5 subscales: appearance, symptoms, 
consciousness, satisfaction with appearance and satisfaction with symptoms.  Each subscale 
consists of a set of items with 4-point categorical responses, scoring 1 to 4 points (with 1 point 
assigned to the most favorable category and 4 assigned to the least favorable). It has been 
demonstrated to be a reliable and valid measure of patients’ perception of scarring12.  
 

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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● 
Photographs of healed wounds will be provided to a third-party, blinded investigator, who will 
evaluate these photos using the validated Visual Analog Scale.   
● 
If the patient’s wound is not healed by 16 weeks, then the patient is deemed to be a treatment 
failure.  The patient will be withdrawn from the treatment part of the study.  The wound care 
instructions will be changed based on the patient’s wound characteristics and medical comorbidities 
and they will continue to receive medical care until their wound is completely healed.  We will 
continue to collect data on these patients until their wounds are completely healed and may describe 
their post-operative wound course in qualitative terms. 
 
 
Statistical Issues 
 
Sample Size/Power 
Time to healing will be the primary outcome measure and will be compared 
between groups using a two-sided t-test.  There is limited literature 
regarding similar patients to help guide estimates for a power analysis. 
Based on a review of the literature,8-10 and a brief review of patients 
previously seen at our clinic, we powered the study to detect a difference in 
healing time between treatment groups of 14 days, and assumed a standard 
deviation (SD) of 15 days. To obtain 80% power to detect such a difference, 
assuming alpha=0.05 and a two-sided t-test, 20 patients per group (40 total) 
are required.  
 
 
 
Anticipated Strengths 
We performed a priori power analysis. We are using a randomized study 
design with validated survey instruments. We plan to use a blinded reviewer 
of the final cosmetic outcome.  
 
Anticipated Limitations 
Given the nature of our study, it will not be possible to conceal treatment 
arm to patients or providers, though assessment of the final outcome will be 
by blinded reviewer. If variability in wound healing is greater than 
anticipated, we may not have statistical power to detect differences between 
groups; however, the estimates we obtain will help inform future studies. 
The minimal debridement group will be seen by the clinician every two 
weeks; while the aggressive debridement group will be seen weekly. It is 
therefore possible that ascertainment of time to wound healing will differ 
between groups. However, we hope to avoid this bias checking with the 
minimal debridement group by phone on weeks where they have no 
scheduled visit. 
 
 

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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Study Calendar / Schematic / Schedule:  
 
Day 1: 
 
Eligible Dermatology patients at Lahey Clinic who have undergone Mohs surgery or excision and have 
postoperative defects allowed to heal by secondary intention, who satisfy the inclusion/exclusion criteria and 
who agree to enter the study and sign the consent form, are randomized to different intervention groups:  
 
Aggressive Debridement Arm vs Minimal Debridement Arm. 
 
Aggressive Debridement Arm: 
 
Week 1-Week 16:  
 
The patient returns to the clinic every week for evaluation until the wound is completely healed, as 
determined by the principal investigator. 
 
Minimal Debridement Arm:  
 
Week 2-Week 16: 
 
The patient returns to the clinic every two weeks for evaluation until the wound is completely healed, as 
determined by the principal investigator. 
 
Potential Risks and Discomforts:  
 
The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of 
themselves than those ordinarily encountered during routine post-operative care, including the performance 
of routine physical or psychological examinations or tests.  However, since this study is comparing two 
methods of treating post-surgical wounds, it is possible that one treatment method is 
significantly more effective than another.  By participating in this study, there is the risk that 
the patients randomized to the less effective treatment method may delay their wound 
healing.  It is also possible that one group of patients may have more side effects than the 
other.  For example, patients in the aggressive debridement group may experience more 
bleeding, pain, and scarring than the minimal debridement group.     
 
Potential Benefits:  
 
Improved knowledge of most effective post-operative secondary intention wound care methods.  
 
 
Statistical Analysis:  
 
Analytic Plan 
Differences in demographic and wound characteristics between groups will 
be compared to evaluate balance between groups. Differences between 
treatments arms for the primary (time-to-healing) and continuous secondary 
outcomes (patient satisfaction with their scar, cosmetic appearance, number 
of complications) will be analyzed using t-tests for independent groups. If 
time-to-healing is not distributed normally, or if there are censored 
observations (e.g., loss to follow-up, or not all patients have healed by the 
16-week endpoint), a log-rank test will be used to test for differences in 

Study Title: Prospective randomized clinical trial comparing outcomes of secondary intention wound 
care methods  
 
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healing time instead of a t-test. Time to healing in both groups will be plotted 
using Kaplan-Meier curves. The proportion of treatment failures in each 
group will be compared using chi-square or exact tests, as appropriate. 
Exploratory subgroup analysis for the above outcomes stratified by 
anatomic site, will be performed to assess for between-group differences 
across wound location. All tests will be two-sided with alpha=0.05. Data will 
be analyzed using at Tufts CTSI using SAS or R software. 
 
Data Management:  
 
All primary data will be maintained by the Principal Investigator  at Lahey Hospital & Medical Center.  An 
electronic copy of de-identified study data will be provided to Dr. Liu, who will be the first author.  De-
identified electronic photographs (i.e. non-full-face photographs showing the scar only) of the final wound will 
be provided to Dr. Dabiri to rank using the Visual Analog Scale. 
 
Data and Safety Monitoring and Quality Assurance:  
 
Data and Safety Monitoring and Quality Assurance will be performed by the Principal Investigator.  As the 
probability and magnitude of harm or discomfort anticipated in the research are not greater in and of 
themselves than those ordinarily encountered during routine post-operative care, there will not be a formal 
Data Safety Monitoring Board (DSMB) for this research. 
 
 
References:  
 
 
 
1. 
Saap, L. J. & Falanga, V. Debridement performance index and its correlation with complete closure 
of diabetic foot ulcers. Wound Repair Regen 10, 354–359 (2002). PMID: 12453138 
2. 
Steed, D. L. Debridement. Am. J. Surg. 187, 71S–74S (2004). PMID: 15147995 
3. 
Hess, C. T. & Kirsner, R. S. Orchestrating Wound Healing: Assessing and Preparing the Wound Bed. 
Advances in Skin & Wound Care 16, 246 (2003). PMID: 14581817 
4. 
Fonder, M. A. et al. Treating the chronic wound: A practical approach to the care of nonhealing 
wounds and wound care dressings. J. Am. Acad. Dermatol. 58, 185–206 (2008). PMID: 18222318 
5. 
Alavi, A. et al. What's new: Management of venous leg ulcers: Treating venous leg ulcers. J. Am. 
Acad. Dermatol. 74, 643–64– quiz 665–6 (2016). PMID: 26979355 
6. 
Wilcox, J. R., Carter, M. J. & Covington, S. Frequency of Debridements and Time to Heal. JAMA 
Dermatol 149, 1050 (2013). PMID: 23884238 
7. 
Luft, H. S. Becoming accountable—opportunities and obstacles for ACOs. N. Engl. J. Med. 363, 
1389–1391 (2010). PMID: 20925539 
8. 
Gloster, H. M., Jr. The use of second-intention healing for partial-thickness Mohs defects involving 
the vermilion and/or mucosal surfaces of the lip. J. Am. Acad. Dermatol. 47, 893–897 (2002). PMID: 
12451375 
9. 
Gohari, S. et al. Evaluation of tissue-engineered skin (human skin substitute) and secondary intention 
healing in the treatment of full thickness wounds after Mohs micrographic or excisional surgery. 
Dermatologic Surgery 28, 1107–14– discussion 1114 (2002). PMID: 12472488 
10. 
Dodson, M. K., Magann, E. F. & Meeks, G. R. A randomized comparison of secondary closure and 
secondary intention in patients with superficial wound dehiscence. Obstet Gynecol 80, 321–324 
(1992). PMID: 1495686 
11. 
Joo, J. et al. Purse-String Suture vs Second Intention Healing. JAMA Dermatol 151, 265 (2015). 
PMID: 25372450 
12. 
Durani, P., McGrouther, D. A. & Ferguson, M. W. The Patient Scar Assessment Questionnaire: A 

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care methods  
 
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Reliable and Valid Patient-Reported Outcomes Measure for Linear Scars. Plastic and Reconstructive 
Surgery 123, 1481–1489 (2009). PMID: 19407619 
13. 
Fearmonti, R., Bond, J., Erdmann, D. & Levinson, H. A review of scar scales and scar measuring 
devices. Eplasty 10, e43 (2010). PMID: 20596233