Clinical trials of a novel non-opioid analgesic have found it to be effective in reducing acute postoperative pain, opening the door to a new way of managing short-term pain that avoids the pitfalls associated with using opioids.
Opioids are effective and routinely prescribed for acute pain. But they raise safety concerns such as respiratory depression (slowed, shallow breathing) and the potential for misuse and addiction. With worldwide medical and research communities claiming that there's an opioid ‘crisis’ or ‘epidemic’, the development of effective non-opioid alternatives is welcomed.
Two phase 2 clinical trials have assessed the efficacy and safety of a new non-opioid analgesic drug in the postoperative setting. The drug, VX-548, works differently from other analgesics by selectively blocking the sodium channel NaV1.8, found on nerves involved in the body’s pain pathways.
In the first trial, 303 participants who’d undergone abdominoplasty, a ‘tummy tuck’, were randomly assigned to receive oral VX-548 in various doses, a combination of hydrocodone bitartrate and acetaminophen (sold as Vicodin), or a placebo to manage postoperative pain over a 48-hour period. The VX-548 group was given either a high dose (100 mg loading dose, then 50 mg every 12 hours) or a mid-range dose (60 mg loading and 30 mg every 12 hours).
The second trial involved 274 participants who’d had bunions removed (bunionectomy) and were similarly divided into three groups. Over 48 hours, the VX-548 group was administered either a high-dose, mid-range dose – the same as in the first trial – or a low dose: a 20 mg loading dose followed by 10 mg every 12 hours.
In both trials, no ‘rescue medication’ was allowed to treat breakthrough pain after the initial dose of VX-548, hydrocodone bitartrate-acetaminophen or placebo, except for ibuprofen, a non-steroidal anti-inflammatory drug (NSAID).
The researchers chose abdominoplasty because it’s considered to be a model of soft-tissue pain and bunionectomy because it’s considered a model of bone pain. Both procedures cause moderate-to-severe postoperative acute pain that’s generally treated with analgesics such as opioids, NSAIDs, and acetaminophen (aka paracetamol).
Participants were asked to rate their pain on a score from zero to 10, with higher scores indicating greater pain, at regular intervals after the first dose of analgesic or placebo was given. They were monitored for adverse effects caused by the drugs.
The researchers found that, compared to the placebo group, VX-548 given at the highest dose reduced acute pain over a 48-hour period after both operations. The lower doses did not show an effect in decreasing acute pain, compared to the placebo. In the abdominoplasty trial, side effects of headache and constipation were more common with VX-548 than with the placebo. VX-548 did not cause respiratory depression or sedation in the participants.
In an accompanying editorial piece, Mark Wallace, an anesthesiologist specializing in pain management, said that while the trials produced promising results, he had some concerns.
“First, ibuprofen, which can be effective in reducing postoperative pain, was allowed as rescue medication, and data on the frequency of use of this drug in the trial groups were not presented,” he said. “Second, … there is little information regarding comparisons between VX-548 and hydrocodone bitartrate-acetaminophen.”
Nonetheless, Wallace is somewhat optimistic about the potential uses of the novel drug.
“It is perhaps disappointing that the effect size of this very original selective peripheral sodium channel blocker was small, and limited conclusions can be made about its effectiveness as compared with other agents because it was not directly compared with hydrocodone-bitartrate-acetaminophen, which is a standard drug for the treatment of acute pain,” he said. “However, these trials represent an early foray into an exciting new class of drugs in a difficult field.”
The study was published in the New England Journal of Medicine.
Source: Vertex Pharmaceuticals via Scimex
