Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).

A Prospective Randomized Trial of an Oral Patient-Controlled Analgesia Device Versus Usual Care Following Total Hip Arthroplasty.

BACKGROUND: Multimodal pain management for surgery patients may include the use of a combination of scheduled oral pain medications with as-needed (PRN) oral opioids. Multiple concurrent time demands on nursing staff frequently cause delays in the delivery of oral PRN pain medication compromising pain management. PURPOSE: Postoperative pain control was compared using a wireless oral patient-controlled analgesia device for the delivery of oxycodone with a control group receiving PRN oxycodone from nursing staff. METHODS: Thirty patients were prospectively randomized into each of 2 groups after total hip arthroplasty. Patient demographics, pain scores, drug dose data, and physical therapy data were collected from chart reviews. Additional data were obtained from patient and nursing surveys. RESULTS: Device patients recorded statistically lower pain scores while taking lower doses of oxycodone on postoperative Day 1 as compared with the control group. Patient surveys indicated that those in the device group reported lower pain scores 24 hours prior to discharge, albeit not statistically different from the control group. Men in the device group reported statistically lower pain scores with physical therapy than men in the control group. Findings from the nursing survey indicate that nurses favored the device over nurse-administered PRN. CONCLUSION: Patients using the wireless patient-controlled analgesia (PCA) (oral) device had less pain at rest and with activity (men) while taking lower doses of oxycodone with each dose. Nursing surveys indicated that nursing staff in this orthopedic postoperative unit found the device easy to use, reliable, and efficient. They also recommended its adoption for those capable of using it.

Nursing time study for the administration of a PRN oral analgesic on an orthopedic postoperative unit.

As needed (PRN) oral opioid analgesics are an integral part of many orthopedic postoperative multimodal pain management regimens. However, the unpredictable nature of this dosing method can lead to disruptions in the process of administering the medication, as well as be an interruption to regular nursing activities. This IRB approved quantitative time study tested the hypothesis that a significant amount of nursing time is required in the administration of PRN oral opioid analgesics on a postoperative orthopedic nursing unit. The purpose of this study is to evaluate the time necessary to complete the required steps related to the administration of PRN oral analgesics. Nurses from 28 nursing shifts used a personal digital assistant (PDA) to record the time needed to complete these steps. We determined that 10.9 minutes is the mean time required to administer PRN oral analgesics on this unit. Other time studies have evaluated the medication administration process as a whole. No time studies related to PRN oral analgesic administration have been reported. In phase I of our project, the data were summarized and will be used as a baseline comparison for phase II, in which we will evaluate an oral PCA medication administration system.