HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial

Abstract

BackgroundHTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine and low-dose meloxicam in a novel polymer that is administered by needle-free application during surgery. The active ingredients are released from the polymer by controlled diffusion over 72 hours. MethodsThis phase 2b, double-blind, placebo-controlled and active-controlled trial enrolled patients undergoing primary unilateral total knee arthroplasty under general anesthesia. Two hundred thirty-two patients were randomized into 4 groups: HTX-011 400 mg bupivacaine/12 mg meloxicam, applied without a needle into the surgical site, the same dose of HTX-011 with a separate 50 mg ropivacaine injection into the posterior capsule, bupivacaine hydrochloride (HCl) 125 mg injection, and saline placebo injection. Only opioids were permitted for postoperative pain rescue. Primary and key secondary endpoints were mean area under the curve of pain intensity scores over 48 hours and 72 hours, respectively, for HTX-011 groups vs placebo. ResultsBoth HTX-011 groups had significantly reduced mean pain intensity vs placebo through 48 and 72 hours (both P < .001). Ropivacaine added a small initial benefit in the first 12 hours. Both HTX-011 groups also had decreased mean pain intensity vs bupivacaine HCl alone through 48 and 72 hours (P < .05). The HTX-011 groups had significantly earlier discharge readiness along with lower opioid consumption through 72 hours. HTX-011 alone or with ropivacaine was well-tolerated with a safety profile similar to controls. ConclusionNeedle-free application of HTX-011 400 mg bupivacaine/12 mg meloxicam provided superior pain reduction through 72 hours after total knee arthroplasty compared with placebo and bupivacaine HCl alone.