A 12-Month Controlled Study in the United States of the Safety and Efficacy of Aquamid® Hydrogel, a Permanent Soft-Tissue Filler

Rodney J. Rohrich, MD, Rhoda S Narins, MD, Fredric S. Brandt, MD, Suzanne Bruce, MD, William P. Coleman III, MD, Lawrence B. Colen, MD, FACS, Steven Dayan, MD, FACS, Richard G. Glogau, MD, Ian T. Jackson, MD, PC, Corey S. Maas, MD, FACS, Gary D. Monheit, MD, Alexander Z. Rivkin, MD, Anthony P. Sclafani, MD, FACS

Background:  A number of soft-tissue fillers are available for cosmetic use to restore volume lost due to aging.  Aquamid® Hydrogel is an injectable, transparent, colorless polyacrylamide hydrogel that acts as a tissue substitute, occupying extracellular space and augmenting skin and underlying tissue depleted due to aging.  Aquamid® Hydrogel is an investigational device in the US, but has been made available in about 40 countries worldwide since it first came to market in 2001.  As Aquamid® Hydrogel is non-resorbable and does not migrate, it offers promise as a longer lasting soft-tissue filler.  For this reason, a comparison of the efficacy and safety of Aquamid® Hydrogel in the aesthetic enhancement of nasolabial folds and that of an active control, the widely used soft-tissue filler Restylane,® was undertaken.

Objective: To demonstrate the non-inferiority in effectiveness of Aquamid® Hydrogel in aesthetic enhancement of nasolabial folds compared to that of an active control six months after end of treatment and to demonstrate the safety of Aquamid® Hydrogel through 12 months following treatment for nasolabial folds.

Methods:  A double-masked, randomized, multi-center study evaluated the safety and efficacy of Aquamid® Hydrogel and the control agent Restylane® in parallel in 315 subjects with nasolabial folds over a period of 12 months.  Subjects were randomly assigned to receive either Aquamid® (N= 210) or Restylane® (N=105) in a 2:1 ratio.  Subjects were allowed up to two touch-up treatments, with a total of three treatments maximum.  The primary effectiveness endpoint was change from baseline in Wrinkle Assessment Scale (WAS) scores (scored 0-5, with higher numbers indicating deeper wrinkles) at six months following the Optimal Treatment Visit, which occurred two weeks after the final treatment.  Adverse events were recorded at each treatment visit.  Subjects also recorded any adverse events in a diary for the two-week period following each injection.

Results:  The primary effectiveness endpoint was met at six months, with Aquamid® Hydrogel demonstrating  non-inferiority to Restylane® in WAS improvement, based on an intent-to-treat analysis.  Effectiveness of Aquamid® Hydrogel was maintained through 12 months.  Mean improvement in WAS score for Aquamid® was 1.8 (± 0.90), which was more than three times the maximum predefined clinically irrelevant difference of 0.5 WAS points.

Secondary endpoints provide further support for the effectiveness of Aquamid® Hydrogel.  The incidence of adverse events, the large majority of which were transient, mild to moderate, and were largely judged as being related to the injection procedure, was similar between groups.  Only one serious adverse event (infection) was thought to be related to treatment and was resolved.

Conclusions:  Aquamid® Hydrogel is as effective as Restylane in aesthetic enhancement of nasolabial folds six months after the last treatment, and continues to be effective through 12 months after treatment.  Aquamid® Hydrogel also appears to be safe and well-tolerated.  As Aquamid® Hydrogel is nonbiodegradable and does not migrate, it is expected that efficacy will continue over a longer period than occurs with Restylane.  A 12-month extension of this study is currently under way to evaluate the longer term safety and efficacy of Aquamid® Hydrogel.

###