Long-term Safety and Effectiveness of Cold-Crosslinked Hyaluronic Acid Fillers: Multicenter, Randomized, Controlled, Double-Blind Study

Summary: In a level-1, randomized, controlled, split-face study of 140 patients with moderate-to-severe nasolabial folds (NLFs), two new cold-crosslinked hyaluronic acid fillers—Evolysse Form (EVLF) and Evolysse Smooth (EVLS)—were compared to Restylane-L (RESL). Each patient received a cold-crosslinked filler in one fold and RESL in the other, with follow-up over 12 months. Both EVLF and EVLS met the primary endpoint by demonstrating noninferiority and, in some cases, statistical superiority to RESL in wrinkle severity reduction. Patient, investigator, and blinded evaluator assessments consistently favored the cold-crosslinked fillers, with significant improvements in FACE-Q scores and a strong safety profile. Overall, EVLF and EVLS were effective and well tolerated, with results lasting up to one year.