Objective  To evaluate the safety and efficacy of cross-linked hyaluronic acid Revanesse Ultra for treatment of nasolabial folds in Chinese population.

  Methods  A total of 120 participants were enrolled in this prospective, randomized, positive controlled, non-inferiority clinical trial in accordance to inclusion and exclusion criteria, and signed informed consents were obtained. The participants were numbered in the order of enrollment and randomized into Restylane group and Revanesse group, receiving hyaluronic acid injection to correct bilateral nasolabial folds. Each person received 1 or 2 times of injection (a touch-up injection could be administered 4 weeks post the first injection). According to the original depth of the wrinkles, no more than 2 ml hyaluronic acid was injected into each side. All the participants were followed up at 1, 3, 6, and 12 months after the last injection and standardized photographs were taken at each visit. All the participants were asked to fill the form of local adverse events within the first 15 days after injection. Investigators and the participants both evaluated wrinkles based on Wrinkle Severity Rating Scale (WSRS). The WSRS score according to the pictures of 6 months post-injection were compared with the pictures which were taken before the injection (baseline) by independent staff at the end of the trial. One or more grades of WSRS improvement compared with the baseline was considered as effective. Laboratory tests including blood and urine routine, liver and renal function tests were carried out at screening visit and 6 months after injection.

  Results  The baseline features between the two groups were comparable (all P > 0.05). There was no significant difference in the WSRS 6 months after injection between the two groups (P > 0.05). There was no significant difference in the WSRS improvement compared with baseline between the two groups (P=0.105). There was no significant difference in the rate of effectiveness between the two groups (93.0% vs. 96.7%, P=0.431). Two participants reported minor adverse events, although both of which might not be associated with the product or procedure. No laboratory test change was found during the trial.

  Conclusions  No severe adverse event associated with the injection material was observed during this clinical trial. According to the result, Revanesse Ultra may have good histocompatibility and tolerance. It could provide obvious improvement in the nasolabial folds, with effectiveness comparable to that of Restylane.