A multisite clinical trial, currently in the recruitment phase, will compare the effectiveness of buprenorphine-naloxone (using Suboxone) and extended-release naltrexone (Vivitrol) in treating opioid use disorders, based on time to relapse. This trial is being funded by the National Institute on Drug Abuse and the EMMES Corporation. Principal investigator John Rotrosen, M.D., professor of psychiatry at the New York University School of Medicine, shared some of the details of the study with ADAW last week.
The purpose of the trial will be to estimate the difference in the time to relapse between the two medications during the six-month trial. Because the medications are so different in so many ways, subjects will not be blinded to the kind of medication they are getting.
The secondary outcomes will be to look at a range of clinical efficacy domains, including craving, to look at demographic, clinical and genetic predictors of effectiveness, and to collect data that will help conduct analyses of costs and benefits.
Patients are being recruited from inpatient detoxification or residential treatment settings, Rotrosen said. Recruitment will be at flexible time points — some patients will be further ahead in the detoxification process than others. “This is an effectiveness study that is trying to mimic and model real-world practice,” he said. All subjects must agree to randomization ahead of time — anyone who wants buprenorphine or Vivitrol specifically would not be in the study, said Rotrosen. Randomization can occur midway through detoxification, or near the end of it. For subjects who are randomized to buprenorphine, induction can be done quickly. If they are randomized to Vivitrol and still are going through detoxification, they will have to stay in the inpatient program long enough to pass a naloxone challenge, he said.
Extensive informed consent
“We have an informed consent that is very extensive,” said Rotrosen. He acknowledged that many opioid users don’t have a clear understanding of Vivitrol — they think it is like a long-term agonist, whereas it is an antagonist. They have to understand the need to be completely detoxified, with no opioids in their system, before being induced.
Will some patients who are randomized to one drug be unhappy that it wasn’t the other? “This is anecdotal rather than data-driven, but yes, there will be some patients who are unhappy to be randomized to Vivitrol, and other patients who are unhappy when randomized to Suboxone,” he said. “One of the eligibility criteria is that patients are expected to be willing to accept either one, so we will be screening out patients who really want one or the other. “
Anyone who drops out of the study during the induction phase or once being treated will be referred to community-based treatment programs, said Rotrosen. “We strongly encourage people to get onto medication,” he said. “We don’t want people to go untreated.”
When the study ends at six months, subjects will be referred to community treatment, just as they will be if they relapse during the trial, he said, adding that all subjects are followed to nine months.
Taper vs. long-term maintenance
For the buprenorphine group, subjects will be given enough medication for a 14-day taper when they leave the study, in case they do not find treatment.
According to Rotrosen, whether maintenance treatment needs to be lifelong is not established yet. “Buprenorphine was developed both as a maintenance medication and as a detox medication,” he said. However, he conceded that “data show that detoxification, whether it’s done with buprenorphine or methadone or clonidine, isn’t good treatment, because people relapse.” Long-term tapers are no better than short-term tapers, he said, citing the Prescription Opioid Addiction Treatment Study of buprenorphine (see ADAW, Nov. 14, 2011). “These are medications that for most people need to be taken for a long time,” said Rotrosen. “I hesitate to say for a lifetime.”
The primary outcome — time to relapse — is the opposite of abstinence. “We expect people to use occasionally,” said Rotrosen. So relapse has been defined as consecutive days and weeks of opioid use.
For more information, go to https://clinicaltrials.gov/ct2/show/NCT02032433.