Four Hyaluronic Acid Fillers for Lip Augmentation

Study Overview
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Brief Summary
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There is need for evidence-based and reproducible data comparing the safety, longevity and patient satisfaction propensity of the various HA soft tissue filler products. Among cosmetic HA soft tissue filler procedures, especially the lip augmentation has become common. Therefore, the aim of this study is to determine whether a statistically significant difference can be detected in the safety, longevity and/or patient satisfaction related to four HA soft tissue filler products widely used for cosmetic lip augmentation. Specifically, the aim of this study is to determine whether superiority of one or more product(s) over the others can be detected.

Detailed Description
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Rationale: Currently, hyaluronic acid (HA) soft tissue fillers are widely employed in cosmetic medical practice for facial contouring and rejuvenation. Among these procedures, especially the lip augmentation has become common. To this end various products have become commercially available, however to date no robust evidence is available to support the safety, longevity or patient satisfaction propensity superiority of one product over the others. Objective: To assess whether superiority in safety, longevity and patient satisfaction propensity can be shown of one of four most frequently used FDA-approved and/or CE marked HA fillers worldwide, used to augment the lip, over the others. Study design: Multi-center, randomized, controlled, four group, parallel, triple-blind clinical trial of 160 adult participants. Study population: Consecutive healthy individuals with no history of previous lip treatment and a self-reported wish for lip augmentation, who present at one of the private cosmetic medicine clinics in the Netherlands, will be recruited. Intervention (if applicable): After giving informed consent, participants will be randomized to receive a protocoled lip augmentation procedure by the injection of either 1 mL of brand A, B, C or D. Main study parameters/endpoints: The primary outcome measure will be the absolute lip volume augmentation as measured by the Lemperle Lip Index from baseline to 3-months follow-up. Secondary outcomes will include the incidence of serious adverse reactions and side effects related to the procedure, the absolute volume augmentation from baseline to 2-weeks follow-up and self-reported quality of life and satisfaction with aesthetic results from baseline to 2-weeks follow-up as measured by validated FACE-Q questionnaire scores.

Official Title
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Safety, Longevity and Patient Satisfaction Comparison of Four Hyaluronic Acid Soft Tissue Fillers in Lip Augmentation: Study Protocol for a Randomized Controlled Clinical Trial

Conditions
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Lip

Intervention / Treatment
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* Procedure: Cosmetic lip augmentation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or over. Female sex. No history of previous lip augmentation treatment. Oral and written informed consent to participate in the study. Desire for cosmetic lip augmentation to improve one's physical or mental well-being. Actively treatment seeking (patient actively chooses to make an appointment at a Faceland private cosmetic clinic without invitation). Small to moderately full lip volume (Merz Lip Scale score 0 - 2 out of 4). Exclusion Criteria: Active peri-oral infection in vicinity of injection site Tumour in vicinity of injection site Active tuberculosis Pregnant or breast-feeding History of severe hypersensitivity to filler components (sodium hyaluronate preparations or local anesthetics of the -amide type, gram-positive proteins, wasps/bees or the hyaluronidase enzyme) Active collagenosis (e.g., active systemic lupus) Graft vs. host disease Active Hashimoto's disease Use of thrombolytics or anticoagulants with high bleeding risk General infection Porphyria Untreated epilepsy Keloid tendency Cardiac arrythmia Severe liver or kidney disease Fulfilling the DSM-5 diagnostic criteria for Body Dyspmorphic Disorder Concurrent laser- peeling- or dermabrasia treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter; triple blind; randomized; parallel; controlled trial with 4 treatment arms (4 different widely used commercially available HA soft tissue fillers with FDA approval status and/or CE-marking for cosmetic facial use).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Juvéderm®<br>Cross-linked hyaluronic acid dermal filler product brand A (1,0 mL at baseline and 0,2 mL touch-up at 2-week follow-up). | Procedure: Cosmetic lip augmentation<br>* The primary study treatment site will be the vermilion (body of the lip); additional areas (vermilion borders, Cupid's bow, philtral columns, and/or oral commissures) will be treated if deemed appropriate by the treating physician. Treatment will be administered through intradermal, subdermal, and/or intramuscular injection within the orbicularis oris muscle. Injection techniques for each area will include linear threading, serial puncture, fanning, and/or cross-hatching. The treating physician will determine the appropriate volume to inject based on clinical experience and the subject's goals for lip augmentation.<br>|
| Experimental: Restylane®<br>Cross-linked hyaluronic acid dermal filler product brand B (1,0 mL at baseline and 0,2 mL touch-up at 2-week follow-up). | Procedure: Cosmetic lip augmentation<br>* The primary study treatment site will be the vermilion (body of the lip); additional areas (vermilion borders, Cupid's bow, philtral columns, and/or oral commissures) will be treated if deemed appropriate by the treating physician. Treatment will be administered through intradermal, subdermal, and/or intramuscular injection within the orbicularis oris muscle. Injection techniques for each area will include linear threading, serial puncture, fanning, and/or cross-hatching. The treating physician will determine the appropriate volume to inject based on clinical experience and the subject's goals for lip augmentation.<br>|
| Experimental: Belotero®<br>Cross-linked hyaluronic acid dermal filler product brand C (1,0 mL at baseline and 0,2 mL touch-up at 2-week follow-up). | Procedure: Cosmetic lip augmentation<br>* The primary study treatment site will be the vermilion (body of the lip); additional areas (vermilion borders, Cupid's bow, philtral columns, and/or oral commissures) will be treated if deemed appropriate by the treating physician. Treatment will be administered through intradermal, subdermal, and/or intramuscular injection within the orbicularis oris muscle. Injection techniques for each area will include linear threading, serial puncture, fanning, and/or cross-hatching. The treating physician will determine the appropriate volume to inject based on clinical experience and the subject's goals for lip augmentation.<br>|
| Experimental: Stylage®<br>Cross-linked hyaluronic acid dermal filler product brand D (1,0 mL at baseline and 0,2 mL touch-up at 2-week follow-up). | Procedure: Cosmetic lip augmentation<br>* The primary study treatment site will be the vermilion (body of the lip); additional areas (vermilion borders, Cupid's bow, philtral columns, and/or oral commissures) will be treated if deemed appropriate by the treating physician. Treatment will be administered through intradermal, subdermal, and/or intramuscular injection within the orbicularis oris muscle. Injection techniques for each area will include linear threading, serial puncture, fanning, and/or cross-hatching. The treating physician will determine the appropriate volume to inject based on clinical experience and the subject's goals for lip augmentation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longevity of absolute lip volume augmentation | The primary outcome will be the longevity of the absolute lip volume augmentation, as measured by the modified Lemperle Lip Index (vertical height in mm). | from baseline to 3-months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient satisfaction (lip appraisal) | Patient satisfaction with the treatment as measured by validated FACE-Q questionnaire Lips score. | from baseline to 3-months follow-up | 
| Quality of Life (Social) | Quality of Life as measured by validated FACE-Q questionnaire Social Function score. | baseline to 3-months follow-up | 
| Quality of Life (Psychological) | Quality of Life as measured by validated FACE-Q questionnaire Psychological Wellbeing score. | baseline to 3-months follow-up | 
| Product safety (serious adverse events) | Product safety, as measured by serious adverse events related to the procedure. | baseline, 2-weeks and 3-months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyaluronic Acid, Dermal Fillers, Lip, Safety, Longevity, Quality of Life, Patient Satisfaction