Journal Article Annotations
2019, 2nd Quarter
Annotations by Walter Luchsinger
Fishman M1, Tirado C, Alam D, Gullo K, Clinch T, Gorodetzky CW; CLEEN-SLATE Team.
This study was a phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of lofexidine for alleviation of OWS symptoms after abrupt opioid withdrawal. Was conducted at 18 US centers from June 2013 to December 2014 and participants were adults who were dependent on short-acting opioids and seeking treatment for OWS. The Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) was chosen as the primary outcome measure because of its validated ability to assess symptom relief during acute opioid detoxification. It is a self-assessed scale with 10 symptom-related items rated from “none” (0) to “severe” (3). There were 603 participants who were randomly assigned into the study. Pairwise differences in overall SOWS-Gossop log-transformed least squares means were statistically significant for lofexidine 2.16 mg (difference, −0.21; 95% CI, −0.37 to −0.04; P = 0.02) and 2.88 mg (−0.26; 95% CI, −0.44 to −0.09; P = 0.003) compared with placebo, indicating greater OWS relief with lofexidine. Study completion rates were significantly higher in the lofexidine groups: 41.5% in the 2.16-mg group. Lofexidine 2.16 mg and 2.88 mg significantly reduced symptoms of OWS versus placebo and increased absolute rates of completing the 7-day study by 14% and 12%, respectively (a relative increase of 85% and 71%). Data suggest that lofexidine is a generally safe and effective nonopioid treatment for opioid withdrawal.
Strength and weaknesses:
Strengths: Randomized, double blind, placebo-controlled study
Weaknesses: The limitations of this study include some facets of its design. Opioid withdrawal is a proximal treatment goal, often necessary but always insufficient to fully manage physiologic opioid dependence. However, the role of lofexidine investigated in this study did not extend beyond its use in the early stage of withdrawal and it was not evaluated with opioid agonist therapy (OAT) or agonist-assisted withdrawal
Opioid use disorder (OUD) is associated with well-known morbidity and mortality, and the current US opioid epidemic has been declared a public health emergency. Lofexidine may have advantages over opioid-based medications for withdrawal management when these are not suitable for certain patients and may provide synergistic benefits when they are inadequate alone. Clonidine will likely have cost advantages over lofexidine (as does any older, generic medication over a newly introduced medication), but although it is routinely prescribed for OWS, it is not FDA-approved for OWS, and therefore does not have OWS labeling, and has not been well-studied to determine appropriate dosing guidelines
Type of study: Multicenter, randomized, double-blind, placebo-controlled study