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Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials

OBJECTIVES: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha(2)-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing in...

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Autores principales: Alam, Danesh, Tirado, Carlos, Pirner, Mark, Clinch, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968526/
https://www.ncbi.nlm.nih.gov/pubmed/32002194
http://dx.doi.org/10.1080/21556660.2019.1704416
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author Alam, Danesh
Tirado, Carlos
Pirner, Mark
Clinch, Thomas
author_facet Alam, Danesh
Tirado, Carlos
Pirner, Mark
Clinch, Thomas
author_sort Alam, Danesh
collection PubMed
description OBJECTIVES: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha(2)-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing information presents these efficacy results using a different, standardized statistical approach that does not transform data or impute missing values. This analysis is easier to interpret and allows comparison across studies. This reanalysis is presented here. METHODS: Studies were double-blind, placebo-controlled for 7 days in Study 1 and 5 days in Study 2. Opioid-dependent adults received placebo or lofexidine; efficacy was assessed using the Short Opioid Withdrawal Scale of Gossop (SOWS-G) daily. RESULTS: Study 1 (N = 602) mean SOWS-G scores were 6.1 (SE: 0.35), 6.5 (SE: 0.34), and 8.8 (SE: 0.47) over Days 1–7 for lofexidine 2.88 mg/day, 2.16 mg/day, and placebo, respectively (for 2.88, p < .0001; for 2.16 mg, p < .0001). Study 2 (N = 264) mean SOWS-G scores were 7.0 (SE: 0.44) and 8.9 (SE: 0.48) over Days 1–5 for lofexidine 2.16 mg/day and placebo, respectively (p = .0037). Median time to treatment discontinuation was approximately 2 days later with lofexidine treatment than with placebo and significantly more lofexidine-treated subjects completed the studies. Hypotension and bradycardia were more common with lofexidine. More placebo subjects withdrew prematurely for lack of efficacy. CONCLUSION: This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in opioid-dependent adults. These results are robust and comparable across studies using various methods of analysis. CLINICALTRIALS.GOV IDENTIFIER: Study 1, NCT01863186; Study 2 NCT00235729. URL: https://clinicaltrials.gov/
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spelling pubmed-69685262020-01-30 Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials Alam, Danesh Tirado, Carlos Pirner, Mark Clinch, Thomas J Drug Assess Addiction Medicine OBJECTIVES: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha(2)-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing information presents these efficacy results using a different, standardized statistical approach that does not transform data or impute missing values. This analysis is easier to interpret and allows comparison across studies. This reanalysis is presented here. METHODS: Studies were double-blind, placebo-controlled for 7 days in Study 1 and 5 days in Study 2. Opioid-dependent adults received placebo or lofexidine; efficacy was assessed using the Short Opioid Withdrawal Scale of Gossop (SOWS-G) daily. RESULTS: Study 1 (N = 602) mean SOWS-G scores were 6.1 (SE: 0.35), 6.5 (SE: 0.34), and 8.8 (SE: 0.47) over Days 1–7 for lofexidine 2.88 mg/day, 2.16 mg/day, and placebo, respectively (for 2.88, p < .0001; for 2.16 mg, p < .0001). Study 2 (N = 264) mean SOWS-G scores were 7.0 (SE: 0.44) and 8.9 (SE: 0.48) over Days 1–5 for lofexidine 2.16 mg/day and placebo, respectively (p = .0037). Median time to treatment discontinuation was approximately 2 days later with lofexidine treatment than with placebo and significantly more lofexidine-treated subjects completed the studies. Hypotension and bradycardia were more common with lofexidine. More placebo subjects withdrew prematurely for lack of efficacy. CONCLUSION: This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in opioid-dependent adults. These results are robust and comparable across studies using various methods of analysis. CLINICALTRIALS.GOV IDENTIFIER: Study 1, NCT01863186; Study 2 NCT00235729. URL: https://clinicaltrials.gov/ Taylor & Francis 2020-01-08 /pmc/articles/PMC6968526/ /pubmed/32002194 http://dx.doi.org/10.1080/21556660.2019.1704416 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Addiction Medicine
Alam, Danesh
Tirado, Carlos
Pirner, Mark
Clinch, Thomas
Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
title Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
title_full Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
title_fullStr Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
title_full_unstemmed Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
title_short Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
title_sort efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials
topic Addiction Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968526/
https://www.ncbi.nlm.nih.gov/pubmed/32002194
http://dx.doi.org/10.1080/21556660.2019.1704416
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