NON-OPIOID SURGICAL PAIN BLOCKER FOR LUMBAR SPINE FIXATION SURGERY: RATIONALE AND DESIGN OF AN ADAPTIVE PHASE II/III CLINICAL TRIAL (STX-103)
HR Jonkman, FR van Tol, S Bruins, S Piluso, A Smorenburg, BJ Oosterman, JJ VerlaanIntroduction & Clinical Challenge
Acute postsurgical pain following lumbar spine fixation surgery remains inadequately managed by current opioid-based regimens, resulting in delayed mobilization, prolonged hospital stays, worse recovery, and an increased risk for chronic postoperative pain (CPSP) and opioid use disorder (OUD). Local anesthetics such as bupivacaine offer a safe and effective opioid-sparing alternative, but current injections work for 24 hours at best, leaving patients undertreated in the most pain-intensive early phase of recovery. Sustained local anesthetic solutions covering the first 72 hours represent a significant unmet need in lumbar spine surgery and are a prerequisite for enhanced recovery and early discharge.
Approach, Methodology & Key Findings
BR-003 is an investigational non-opioid surgical pain blocker. It consists of a ring-shaped biodegradable hydrogel placed intraoperatively at the fixation site, around the pedicle screw. After surgery, it provides a controlled local bupivacaine release for more than three days without changing the current surgical workflow. In a Phase Ib clinical trial, BR-003 demonstrated sustained local drug availability with favorable safety results, as well as an early indication of efficacy in terms of reductions in postoperative pain and opioid consumption. The STX-103 study is designed to evaluate the efficacy and safety of BR-003 in adults undergoing primary single-level lumbar fixation. It is an adaptive prospective, multicenter, double-blind randomized controlled trial consisting of a Phase II part (n=24) and a Phase III part (n=176) within the same protocol. The primary endpoint is acute postsurgical pain, expressed as the Area Under the Curve (AUC) of the Numeric Rating Scale of back pain intensity in rest (NRS-R) during the first 72 hours. For the intercurrent event rescue opioids, a windowed last observation carried forward (wLOCF) is applied. The key secondary endpoint is cumulative opioid use in Morphine Milligram Equivalents (MME) during the first 72 hours. Other endpoints include length of hospital stay, postoperative mobilization and recovery, safety assessments (including adverse events, ECGs, radiographs, blood chemistry, clinical & neurological outcomes), and pharmacokinetics up to six weeks. In addition, up to one year, patients will report health-related quality of life, functional outcomes, healthcare utilization, and return to work and normal activities. Both the intervention and control group will receive a fully standardized perioperative pain protocol. Phase II results will inform a pre-specified interim analysis for sample size re-estimation and protocol adaptation prior to Phase III. The trial will be conducted in Europe, and its design has been reviewed by EMA as part of a scientific advice request.
Discussion
BR-003 addresses the mechanistic gap in current local anesthetic approaches by delivering bupivacaine where and when it is needed without increasing perioperative complexity. By providing sustained local pain relief whilst reducing the need for opioids, it is designed to be integrated with Enhanced Recovery After Surgery (ERAS) protocols for lumbar fixation and promote earlier discharge and better patient outcomes. Beyond acute pain relief, the opioid-sparing mechanism of BR-003 has the potential to reduce downstream clinical and economic burden associated with prolonged hospital stays, opioid-related adverse events, and the development of CPSP and OUD. If the primary endpoint is confirmed, this trial will generate the first prospective pivotal dataset on implantable local anesthetics in lumbar fixation, with direct implications for regulatory approval, multimodal opioid-sparing analgesia, and ERAS adoption in surgical practice.