Tacrolimus for Malar Edema

October 19, 2018 updated by: Richard Warren, University of British Columbia

Malar Bags After Lower Lid Blepharoplasty and Facelift: A Randomized Controlled Trial of the Effects of Tacrolimus

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4J7
        • Recruiting
        • Vancouver Plastic Surgery Center
        • Contact:
          • Richard Warren, MD
          • Phone Number: 604-876-1774
        • Contact:
          • Tracy Stuby

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tacrolimus Treatment
Tacrolimus Topical 0.1% Topical Ointment
Drug: Tacrolimus Topical 0.1% Topical Ointment
Topical tacrolimus ointment
Other Names:
  • Protopic
Placebo Comparator: Control
Patients will be self matched controls with one cheek receiving the study ointment and the other receiving a control ointment (polysporin ointment).
Drug: Polysporin Ointment
Polysporin ointment
Other Names:
  • Polysporin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Malar edema
Time Frame: 6 months
Development of malar edema post operatively
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Investigators

  • Principal Investigator: Richard Warren, MD, University of British Columbia
  • Study Chair: Stahs Pripotnev, MD, University of British Columbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2018

Primary Completion (Anticipated)

July 1, 2019

Study Completion (Anticipated)

July 1, 2019

Study Registration Dates

First Submitted

October 19, 2018

First Submitted That Met QC Criteria

October 19, 2018

First Posted (Actual)

October 23, 2018

Study Record Updates

Last Update Posted (Actual)

October 23, 2018

Last Update Submitted That Met QC Criteria

October 19, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H17-02969

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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