Joshua D Lee1, Edward V Nunes2, Patricia Novo Mpa3, Genie L Bailey4, Gregory S Brigham5, Allan J Cohen6, Marc Fishman7, Walter Ling8, Robert Lindblad9, Dikla Shmueli-Blumberg9, Don Stablein9, Jeanine May9, Dagmar Salazar9, David Liu10, John Rotrosen3. 1. New York University School of Medicine, New York, NY, United States. Electronic address: joshua.lee@nyumc.org. 2. New York State Psychiatric Institute, Columbia University Medical Center, New York, NY, United States. 3. New York University School of Medicine, New York, NY, United States. 4. Warren Alpert Medical School, Brown University, Providence, RI, United States; Stanley Street Treatment & Resources, Fall River, MA, United States. 5. Adapt, Roseburg, OR, United States. 6. Bay Area Addiction Research & Treatment, San Francisco, CA, United States. 7. Mountain Manor Treatment Center, Baltimore, MD, United States. 8. UCLA Integrated Substance Abuse Program, Los Angeles, CA, United States. 9. The Emmes Corporation, Rockville, MD, United States. 10. National Institute on Drug Abuse, Rockville, MD, United States.
Abstract
INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. CONCLUSIONS: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. CLINICAL TRIAL REGISTRATION: NCT02032433.
RCT Entities:
INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. CONCLUSIONS:XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. CLINICAL TRIAL REGISTRATION: NCT02032433.
Authors: Daniel Wolfe; M Patrizia Carrieri; Nabarun Dasgupta; Alex Wodak; Robert Newman; R Douglas Bruce Journal: Lancet Date: 2011-04-30 Impact factor: 79.321
Authors: Raymond F Anton; Stephanie S O'Malley; Domenic A Ciraulo; Ron A Cisler; David Couper; Dennis M Donovan; David R Gastfriend; James D Hosking; Bankole A Johnson; Joseph S LoCastro; Richard Longabaugh; Barbara J Mason; Margaret E Mattson; William R Miller; Helen M Pettinati; Carrie L Randall; Robert Swift; Roger D Weiss; Lauren D Williams; Allen Zweben Journal: JAMA Date: 2006-05-03 Impact factor: 56.272
Authors: Evgeny Krupitsky; Edward V Nunes; Walter Ling; Ari Illeperuma; David R Gastfriend; Bernard L Silverman Journal: Lancet Date: 2011-04-30 Impact factor: 79.321
Authors: Lesia M Ruglass; Jennifer Scodes; Martina Pavlicova; Aimee N C Campbell; Skye Fitzpatrick; Celestina Barbosa-Leiker; Kathleen Burlew; Shelly F Greenfield; John Rotrosen; Edward V Nunes Journal: Drug Alcohol Depend Date: 2019-10-21 Impact factor: 4.492
Authors: Scott E Hadland; J Frank Wharam; Mark A Schuster; Fang Zhang; Jeffrey H Samet; Marc R Larochelle Journal: JAMA Pediatr Date: 2017-08-01 Impact factor: 16.193
Authors: Marc Fishman; Kevin Wenzel; Jennifer Scodes; Martina Pavlicova; Joshua D Lee; John Rotrosen; Edward Nunes Journal: J Adolesc Health Date: 2020-08-29 Impact factor: 5.012
Authors: Celestina Barbosa-Leiker; Aimee N C Campbell; Martina Pavlicova; Jennifer Scodes; A Kathleen Burlew; Mary Hatch-Maillette; Sarah E Mennenga; Shannon G Mitchell; Patricia Novo; Edward V Nunes; John Rotrosen; Shelly F Greenfield Journal: Am J Addict Date: 2020-05-21
Authors: Angela M Haeny; LaTrice Montgomery; A Kathleen Burlew; Aimee N C Campbell; Jennifer Scodes; Martina Pavlicova; John Rotrosen; Edward Nunes Journal: Addict Behav Date: 2020-06-18 Impact factor: 3.913
Authors: Brantley P Jarvis; August F Holtyn; Shrinidhi Subramaniam; D Andrew Tompkins; Emmanuel A Oga; George E Bigelow; Kenneth Silverman Journal: Addiction Date: 2018-03-24 Impact factor: 6.526
Authors: Kathryn E McCollister; Jared A Leff; Xuan Yang; Joshua D Lee; Edward V Nunes; Patricia Novo; John Rotrosen; Bruce R Schackman; Sean M Murphy Journal: Am J Manag Care Date: 2018-11 Impact factor: 2.229
Authors: Edward V Nunes; Joshua D Lee; Dominic Sisti; Andrea Segal; Arthur Caplan; Marc Fishman; Genie Bailey; Gregory Brigham; Patricia Novo; Sarah Farkas; John Rotrosen Journal: Contemp Clin Trials Date: 2016-09-28 Impact factor: 2.226
Authors: Joshua D Lee; Edward V Nunes; Patricia Novo; Ken Bachrach; Genie L Bailey; Snehal Bhatt; Sarah Farkas; Marc Fishman; Phoebe Gauthier; Candace C Hodgkins; Jacquie King; Robert Lindblad; David Liu; Abigail G Matthews; Jeanine May; K Michelle Peavy; Stephen Ross; Dagmar Salazar; Paul Schkolnik; Dikla Shmueli-Blumberg; Don Stablein; Geetha Subramaniam; John Rotrosen Journal: Lancet Date: 2017-11-14 Impact factor: 79.321