5-fluorouracil Versus Placebo in Periocular Full Thickness Skin Grafts
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|ClinicalTrials.gov Identifier: NCT02705352|
Recruitment Status : Terminated (Low enrollment)
First Posted : March 10, 2016
Last Update Posted : January 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Ectropion Skin Neoplasms||Drug: 5-Fluorouracil Other: Normal saline||Phase 2|
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In oculofacial surgery, full thickness skin grafts are a fundamental tool used to restore function to the eyelid. This can be required after removal of skin cancer, correction of eyelid malposition such as cicatricial eyelid ectropion (the eyelid edge is pulled away from the eye), retraction (the eyelid is pulled lower than normal, exposing more of the eye to the air), scar formation (such as a medial pulling or web), or trauma with loss of tissue. These conditions affect patients of all ages, ranging from newborns to nonagenarians. Skin grafting in the periorbital area is relatively safe, although complications may arise. The most common and challenging complication scarring and graft shrinkage. This can lead to requiring additional surgery to add additional skin or to improve the appearance of the graft. In addition to the morbidity of another surgery, some patients have limited or no additional skin available (e.g. young patients, burn patients). The eyelid skin is the thinnest of the body, so only thin skin can be used as donor material. However, the amount of skin available for this purpose is very little.
There are limited options for preventing graft shrinkage and scarring in this situation. The oldest and most commonly used technique is injection of steroid medication. Steroids decrease proliferation of a fibroblast cells, which create collagen and glycosaminoglycan, two proteins created by the body that contract and cause graft shrinkage. Data in literature shows that one form of steroid, triamcinolone, is effective for this purpose. However, there is a risk of embolization of this solid steroid material that care rarely cause blindness. In addition, in the periocular area, steroids can elevate eye (intraocular) pressure (that can cause glaucoma in some cases) and accelerate the formation of cataracts.
Another medication used for this purpose is 5-fluorouracil (5-FU). This is an antimetabolite (a drug that inhibits another chemical that is part of normal processes) that works by irreversibly inhibiting the enzyme thymidylate synthetase resulting in impaired DNA synthesis. This reduces fibroblast proliferation and inhibits collagen type 1 production which is a key protein in scar formation. This medication is commonly used in ophthalmology after glaucoma filtration surgery. In this usage, it is injected under the conjunctiva to prevent scarring around the surgical site.
There have been two retrospective studies that have investigated the safety and efficacy of 5-FU injected in periorbital skin grafts with or without Kenalog. The first (Massry 2011) used post-operative injections of a 50:50 mixture of 5-FU and triamcinolone for correction of medial canthal webs. In 2 patients, they found it to be safe and effective. The author noted he has used it previously for other scar management cases and was "very pleased with the results and [had] negligible side-effect[s]." The same author performed another study using 5-FU for skin grafts. This study evaluated 19 patients who had skin grafts for various purposes and were injected following surgery (similar to our protocol). This study demonstrated safety of the injection, with no cases of complication. The author concluded that the 5-FU is effective with "minimal scarring, high patient and surgeon satisfaction, and few complications." However, there was no comparison group to truly evaluate the effect. With only two retrospective studies by the same author, there is no strong evidence that it is effective, although safety has been demonstrated.
The investigators therefore propose a randomized controlled prospective study to evaluate the outcomes of periocular skin grafts with or without the use of 5-FU injected in the post-operative period. Patients will be recruited from the investigators' practices who need full thickness skin grafts for reconstruction after cancer removal, pre-existing scarring, eyelid malposition, or trauma. Patients will be introduced to the study, and will come back for detailed explanation and consent. The injection medication will be prepared by the Mass Eye and Ear Research Pharmacy and labeled for this double-blinded study. Injections will be given 2-3 weeks after surgery and up to 4 times (also every 2-3 weeks). Measurements and photographs of the skin graft will be taken at each visit (following injections, at 3, 6, and 12 months) to monitor for complications. Patients will be followed for at least 12 months.
If effective, this medication could change the post-operative management of skin grafts, reduce complications and reoperations.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Prospective, Randomized, Double-blinded Comparison of the Use of 5-fluorouracil Versus Placebo in Periocular Full Thickness Skin Grafts.|
|Actual Study Start Date :||August 25, 2016|
|Actual Primary Completion Date :||January 25, 2019|
|Actual Study Completion Date :||January 25, 2019|
Antimetabolite will be injected 2 weeks after periocular reconstruction with full thickness skin graft. Injection will be repeated every 2 weeks for a total of up to 4 injections.
Other Name: 5-FU
Placebo Comparator: Normal saline
Normal saline will be injected 2 weeks after periocular reconstruction with full thickness skin graft. Injection will be repeated every 2 weeks for a total of up to 4 injections.
Other: Normal saline
Other Name: Saline
- Graft change [ Time Frame: 12 months ]Full thickness skin grafts will be measured prior to treatment (at time of surgery) and 12 months after surgery. Although the graft will be measured at each visit, the outcome is the final size at 12 months.
- Adverse events [ Time Frame: 12 months ]Treatment side effects will be recorded. Examples include pain, skin thinning, color/texture change, atrophy, telangiectasis, infection, and erythema.
- Early post-operative complications [ Time Frame: 2 weeks after surgery ]Surgery complications will be recorded, not related to treatment. Examples are wound dehiscence, graft necrosis, infection, bleeding, partial/complete graft failure and/or ectropion.
- Surgeon and Patient satisfaction [ Time Frame: 12 months ]Surgeon and patient satisfaction will be evaluated using a scar assessment scale (POSAS) at each visit. Questionnaire developed and previously published by Draaijers et al 2004.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02705352
|United States, Massachusetts|
|Massachusetts Eye and Ear Infirmary|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Michael K Yoon, MD||Massachusetts Eye and Ear Infirmary|