03450nam a2200313   4500001000800000007000300008008004100011040000800052041000800060100003200068245005600100300002300156520249400179650002502673650003302698650001702731650001602748650002602764650002102790700003002811700002402841700002802865700002602893700003102919700002802950773011002978942003103088999001703119ESSALUDta      t        pe ||||| |||| 00| 0 spa d  aBMG  aspa  aSingla, Neil eAutor953819  aPhase 2b Trial of a NaV1.8 inhibitor for acute pain  apáginas: 454-464  aBackground: Nav1.8, a voltage-gated sodium channel expressed in the peripheral nervous system, has a critical role in pain signaling. Previous trials of NaV1.8 inhibitors have shown effectiveness in reducing postoperative pain. Methods: We conducted a phase 2b, double-blind, randomized, placebo-controlled trial to evaluate LTG-001, a selective Nav1.8 inhibitor, in patients with moderate-to-severe pain after abdominoplasty. Patients were randomly assigned in a 1:1:1:1 ratio to receive a 300-mg loading dose of LTG-001, followed by 150 mg every 12 hours (low-dose group); a 450-mg loading dose of LTG-001, followed by 300 mg every 12 hours (high-dose group); hydrocodone bitartrate–acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen) every 6 hours; or placebo every 6 hours. All doses were administered orally over a 48-hour period. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour treatment period (SPID48), based on scores on the Numeric Pain Rating Scale (range, 0 to 10, with higher values indicating more severe pain; higher SPID48 values indicate greater pain reduction). Secondary end points included the amount of opioid rescue medication consumed in morphine milligram equivalents (MME) and no receipt of opioid rescue medication.
Results: A total of 343 patients underwent randomization. The least-squares mean SPID48 was 161.05 (95% confidence interval [CI], 142.93 to 179.16) in the low-dose group, 185.30 (95% CI, 167.26 to 203.34) in the high-dose group, 164.08 (95% CI, 146.02 to 182.14) in the hydrocodone bitartrate–acetaminophen group, and 123.22 (95% CI, 105.23 to 141.21) in the placebo group. The least-squares mean difference in the SPID48 between LTG-001 and placebo was significant for each dose (low dose: 37.82 [P=0.003]; high dose: 62.08 [P<0.001]), and that between hydrocodone bitartrate–acetaminophen and placebo was 40.86. High-dose LTG-001, but not low-dose LTG-001, was associated with significantly lower opioid use than placebo (11.00 MME vs. 18.35 MME, P=0.01), as well as a significantly higher percentage of patients who received no opioid rescue medication (52% vs. 22%, P<0.001). High-dose LTG-001 was associated with a higher incidence of pyrexia than placebo (7% vs. 2%) and a higher incidence of presyncope (6% vs. 1%).
Conclusions: LTG-001 led to significantly greater reductions in pain scores than placebo over the course of 48 hours after abdominoplasty.  aDERMATOLOGÍA97479  aMEDICINA DE URGENCIAS953820  aNEUROLOGÍA  aOBSTETRICIA  aOFTALMOLOGÍA932364  aORTOPEDIA925652  aP. Katz, Nathaniel953821  aVaughn, Ben 953822  aRogier, Timothy 953823  aBertoch, Todd 953824  aMinkowitz, Harold  953825  aLoflin, Mallory 9538260 022717922638dMassachusetts NEJM GroupoNEJM005tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-07-31zSQB  c22752d22752