Clinical trial NCT03715387: Tacrolimus for Malar Edema
Official title: Malar Bags After Lower Lid Blepharoplasty and Facelift: A Randomized Controlled Trial of the Effects of Tacrolimus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Edema Face
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2018-10-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Patients will serve as their own self matched controls with one study cheek and one control cheek.
Primary purpose: PREVENTION

Brief summary: Elective lower eyelid surgery is a common cosmetic procedure. Facial swelling is a common complication. Studies suggest that this facial swelling is part of a complex inflammatory process. Topical tacrolimus has long been used to treat various inflammatory skin disorders. By combining our knowledge of facial swelling and tacrolimus mechanism of action, we can hypothesize that it can be used as a treatment to prevent this post-operative swelling. The purpose of this project is to apply topical tacrolimus to one of the patient's cheeks following facial surgery and compare the incidence of facial swelling to the opposite side control cheek.

Detailed description: 1.0 Purpose:

To perform a randomized controlled trial to determine if topical tacrolimus ointment reduces incidence or severity of post-operative facial edema and malar bags after elective blepharoplasty and/or facelift.

2.0 Hypothesis:

Topical tacrolimus will reduce the incidence and severity of post-operative facial edema presenting as malar bags after blepharoplasty and/or facelift.

3.0 Justification:

Elective blepharoplasty is the fourth most common cosmetic procedures performed in North America. According to a report published by the American Society of Plastic Surgery, eye lid surgery accounted for 209,000 out of the 1.7 million cosmetic surgical procedures performed in 2016. Additionally, the number of eye lid surgeries rose 2% in 2016 compared to 2015 \[ref 1\].

Recurrent or worsened malar bags is a common complication of lower lid surgery. Studies suggest that post-operative lymphedema is a possible cause of these malar bags. Recent research into lymphedema pathophysiology shows that post-operative lymphedema is not simply a result of direct lymphatic injury, but rather a complex fibroproliferative inflammatory process.

Topical tacrolimus has long been used to treat various inflammatory skin disorders such as atopic dermatitis and psoriasis safely and effectively. By combining our knowledge of lymphedema pathophysiology and tacrolimus mechanism of action, we can hypothesize that it can be effectively used as a treatment to prevent post-operative malar bags as a result of lymphedema.

4.0 Objectives:

4.1. To apply topical tacrolimus ointment to a randomized cheek in sequential patients undergoing lower lid blepharoplasty, facelift or both and compare to the contralateral control cheek.

4.2. To determine if topical tacrolimus affects the incidence and severity of post-operative malar edema compared to the self-matched contralateral control cheek.

5.0 Research Design:

This is a double blinded randomized controlled trial involving an initial surgery followed by random topical drug treatment that is self matched to a contralateral control side. There will be 3 follow up visits for analysis.

6.0 Statistical Analysis:

6.1 Statistical Considerations

The primary endpoint is post operative malar edema which typically occurs 10-20% of the time following lower lid blepharoplasty and/or facelift procedures. If we expect to reduce the occurrence to 1-5% the number of patients required to achieve a significant result (α = 0.05 (2-sided), β = 0.20) is 40-100.

No increase in sample size has been made to account for losses to follow-up. In our practice over the past 10 years we have found that less than 1% of patients do not return for a follow-up visit.

6.2 Outcome Measures

A custom four point scale will be used to record the outcomes for each cheek:

I: No post operative edema. II: Mild post operative edema. III: Moderate post operative edema. IV: Severe post operative edema.

Example photographs will be provided to the blinded rater for each category.

6.3 Data Collection

Outcome measurements will be performed by a single observer who will be blinded to the contents of the containers and which cheek either was applied to. Data will be collected on study specific data collection forms.

7.0 Procedure

7.1 Surgical Procedure

The lower lid blepharoplasty and facelift procedures will be performed by Dr. Richard Warren in the usual fashion based on the patient's presenting problem. Specific differences in technique such as skin only excision vs fat transposition and ORL (Orbicularis Retaining Legament) division will be recorded and analyzed separately.

7.2 Tacrolimus Application

Patients will be given two containers labelled with "Right" and "Left" to be applied to their right and left cheeks respectively. The patients will apply the ointment once daily for 4 weeks post operatively. The contents of the containers will be randomized to either the treatment tacrolimus ointment or the control ointment which will be matched in colour and consistency to the tacrolimus ointment. They will be given instructions on applying the ointments based on FDA recommendations.

7.3 Choice of Tacrolimus Dose

The treatment containers will contain 0.1% tacrolimus ointment (marketed as PROTOPIC) based on FDA recommendations for adult patients. This dose of the drug is known to be sufficiently absorbed by inflamed skin reaching peak concentrations of 0.05-0.25ng/ml 3-6 hours after application. This is significantly lower than the accepted safe level of 5-20ng/ml established based on transplant research. \[ref 16,17\]

7.4 Post-operative Treatment

Patients will be followed post operatively in the office at 1 week, 4 weeks, and 6 months. Degree of post operative malar edema will be assessed by a single blinded observer. This will be recorded using a four point scale. Any side effects or adverse events will also be recorded.

Eligibility criteria: Inclusion Criteria:

* Bilateral lower lid blepharoplasty, facelift, or both.
* Patients over 18 years of age.

Exclusion Criteria:

* -Patients presenting for revision surgery.
* Patients with a known allergy to tacrolimus.
* Patients taking medications that alter tacrolimus metabolism:
* Anticonvulsants: carbamazepine, phenobarbital, phenytoin
* Antibiotics: rifampicin, rifabutin
* Antifungal: clotrimazole, ketoconazole, fluconazole, itraconazole
* Ca++ channel blockers: diltiazem, nifedipine, nicardipine, verapamil
* Macrolides: erythromycin, clarithromycin, troleandomycin
* Miscellaneous: cyclosporin A, danazol, bromocriptine, cimetidine, methylprednisolone, protease inhibitors
* Patients with previously diagnosed reduced kidney function.
* Immunocompromised patients.
* Patients with a history of cutaneous facial malignancies.
* Patients with active cutaneous facial infections.

Primary outcomes:
measure: Malar edema
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver Plastic Surgery Center
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Richard Warren, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Stahs Pripotnev, MD
role: STUDY_CHAIR
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