Tacrolimus for Malar Edema

NCT ID: NCT03715387

Last Updated: 2018-10-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-10
• Study Completion Date: 2019-07-01

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.

Conditions

Edema Face

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Tacrolimus Treatment

Tacrolimus Topical 0.1% Topical Ointment

Group Type: EXPERIMENTAL

Tacrolimus Topical 0.1% Topical Ointment

Intervention Type: DRUG

Topical tacrolimus ointment

Control

Patients will be self matched controls with one cheek receiving the study ointment and the other receiving a control ointment (polysporin ointment).

Group Type: PLACEBO_COMPARATOR

Polysporin Ointment

Intervention Type: DRUG

Polysporin ointment

Interventions

Tacrolimus Topical 0.1% Topical Ointment

Topical tacrolimus ointment

Intervention Type: DRUG

Polysporin Ointment

Polysporin ointment

Intervention Type: DRUG

Other Intervention Names

Protopic; Polysporin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Richard Warren

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Warren, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Stahs Pripotnev, MD

Role: STUDY_CHAIR

University of British Columbia

Locations

Vancouver Plastic Surgery Center

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Richard Warren, MD

Role: CONTACT

tracy@drwarren.ca

604-876-1774

Tracy Stuby

Role: CONTACT

tracy@drwarren.ca

604-876-1774

Facility Contacts

Richard Warren, MD

Role: primary

604-876-1774

Tracy Stuby

Role: backup

References

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Other Identifiers

H17-02969

Identifier Type: -

Identifier Source: org_study_id