Background & Aims
There is a troubling lack of effective pain treatments after major surgery. Opioids remain dominant despite their many drawbacks, resulting in worse clinical outcomes and higher costs. Locoregional anesthetics are increasingly employed, but their added value remains limited by their short duration of effect.
BR-003 is an implantable anesthetic designed for spine fixation surgery. It consists of a ring-shaped biodegradable hydrogel that is easily co-implanted with pedicle screws. Unlike injections, BR-003 stays in place and delivers bupivacaine to the surgical site for three days before dissolving in the body completely.
By reducing pain and opioid-related side-effects, BR-003 may help patients leave the hospital sooner and in better shape. Now, it is being tested in humans for the first time, to assess safety and obtain an early indication of efficacy.
Methods
Open-label Phase Ib clinical trial on BR-003 safety and pharmacokinetics. Two cohorts of 6 patients were scheduled for posterior degenerative spine fixation in two hospitals. Cohort 1 received 4 pedicle screws with 4 BR-003 rings. Cohort 2 received 6 screws and 6 rings. In both cohorts, 3 patients were planned for minimally invasive surgery (MIS) and 3 for open procedures. The primary endpoint was the peak serum concentration of bupivacaine (Cmax). Secondary endpoints included additional pharmacokinetics, safety, and exploratory efficacy up to 6 weeks. Safety monitoring included adverse events, ECGs, X-rays, and blood biochemistry. Efficacy was explored by comparing back pain in rest (AUC-NRS-R) and opioid use (Morphine Milligram Equivalents, MMEs) in the first three days to a recent observational cohort undergoing the same type of surgery by the same surgeons in the same hospitals. In MIS cohort 1, pre-emptive analgesia was restricted to assess the early effects of BR-003.
Results
Eleven patients were included in the study in total. The measured bupivacaine Cmax remained 10x below the known toxic threshold of 2000 ng/mL. No serious adverse events were attributed to BR-003 to date. In the first three days after surgery, total opioid use was 52% lower with BR-003 (mean MME 231 vs. 111), with a 36% reduction in back pain in rest (mean AUC-NRS-R 4.2 vs. 2.7). Opioid use on day 2 and 3 was low, providing opportunities for earlier discharge.
Conclusions
This first-in-human study with BR-003 revealed no safety concerns to date. A substantial reduction in pain and opioid use was found as compared to a recent observational cohort in the same hospitals. A large randomized controlled trial is planned to substantiate the impact of BR-003 on pain, opioid use, and enhanced recovery after spine fixation surgery.
References
N/A
Presenting Author
Hein Jonkman
Poster Authors
Hein Jonkman
MD, MSc
Radboud University Medical Center, SentryX, The Netherlands
Lead Author
Suzanne Bruins
SentryX, the Netherlands
Lead Author
Floris Rudolf van Tol
MD
SentryX, University Medical Center Utrecht, the Netherlands
Lead Author
Jasper Gerard Steverink
MD
SentryX, University Medical Center Utrecht, the Netherlands
Lead Author
Lorin Benneker
MD
Sonnenhof Hospital, Bern, Switzerland
Lead Author
Ruth Geuze
MD
Elizabeth Two Cities Hospital, Tilburg, the Netherlands
Lead Author
Paul De Baat
MD
Catharina Hospital
Lead Author
Bas Jeroen Oosterman
PhD
SentryX, the Netherlands
Lead Author
Jorrit-Jan Verlaan
MD
University Medical Center Utrecht, SentryX, The Netherlands
Lead Author
Topics
- Specific Pain Conditions/Pain in Specific Populations: Acute Pain and Nociceptive Pain