Investigational Sodium Channel Blocker Effective at Reducing Acute Pain After Surgery
According to study results published in The New England Journal of Medicine, the use of high doses of investigative drug VX-548 (Vertex Pharmaceuticals, Boston, MA), a selective inhibitor of the Nav1.8 sodium ion channel, may be effective in reducing acute pain after surgeries, including abdominoplasty and bunionectomy. Nav1.8 is a voltage-gated sodium channel that plays a role in pain signaling in the peripheral nervous system.
The published results comprise 2 double-blind, placebo-controlled phase 2 studies, one including 303 participants who underwent abdominoplasty (NCT05034952) and the other including 274 participants who underwent bunionectomy (NCT04977336). Participants who underwent abdominoplasty were randomly assigned to a high dose group for VX-548 (100 mg loading dose with 50 mg maintenance doses every 12 hours), a middle dose group for VX-548 (60 mg loading dose with 30 mg maintenance doses every 12 hours), a hydrocodone bitartrate–acetaminophen group, or an oral placebo group. For the bunionectomy study, participants were randomized to a high dose group for VX-548, a middle dose group for VX-548, a low dose group for VX-548 (20 mg loading dose with 10 mg maintenance dose every 12 hours), a hydrocodone bitartrate–acetaminophen group, or an oral placebo group. Treatment in all groups was administered over a 48-hour period. Researchers assessed time-weighted sum of pain-intensity difference over 48 hours (SPID48) measured by Numeric Pain Rating Scale (NPRS).
After 48 hours, the least-squares mean difference in pain intensity (SPID48) between those in the high-dose VX-548 group and those given placebo was 37.8 (95% CI, 9.2-66.4) in the abdominoplasty trial and 36.8 (95% CI, 4.6-69.0) in the bunionectromy trial suggesting that high doses of VX-548 can reduce acute pain after surgery. The middle dose and low dose of VX-548 groups showed pain reduction similar to that seen with placebo, indicating that higher doses of the drug are needed. Common reported adverse events were mild or moderate for high-dose VX- 548 and included headache and constipation.