Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations

Theresa Winhusen¹, Michelle Lofwall², Hendrée E Jones³, Christine Wilder⁴, Robert Lindblad⁵, Davida M Schiff⁶, Scott Wexelblatt⁷, Stephanie Merhar⁷, Sean M Murphy⁸, Shelly F Greenfield⁹, Mishka Terplan¹⁰, Elisha M Wachman¹¹, Frankie Kropp⁴, Jeff Theobald⁴, Mitra Lewis⁵, Abigail G Matthews⁵, Connie Guille¹², Michael Silverstein¹³, Carmen Rosa¹⁴

Affiliations

¹ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA; Center for Addiction Research, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA. Electronic address: winhusen@carc.uc.edu.
² Departments of Behavioral Science and Psychiatry, University of Kentucky College of Medicine, Center on Drug and Alcohol Research, 845 Angliana Avenue, Lexington, KY 40508, USA.
³ UNC Horizons and Department of Obstetrics and Gynecology, University of North Carolina Chapel Hill, 410 North Greensboro St., Carrboro, NC 27510, USA.
⁴ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA; Center for Addiction Research, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA.
⁵ The Emmes Company, LLC, 401 N Washington Street, Suite 700, Rockville, MD 20850, USA.
⁶ Division of General Academic Pediatrics, MassGeneral Hospital for Children, 125 Nashua St Suite 860, Boston, MA 02114, USA.
⁷ Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Avenue, Cincinnati, OH 45229, USA.
⁸ Department of Healthcare Policy & Research, Weill Cornell Medical College, 425 East 61st Street Suite 301, New York, NY 10065, USA.
⁹ Department of Psychiatry, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Division of Alcohol, Drug and Addictions and the Division of Women's Mental Health, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
¹⁰ Friends Research Institute,1040 Park Ave Suite 103, Baltimore, MD 21201, USA.
¹¹ Department of Pediatrics, Boston Medical Center, 801 Albany Street, Boston, MA 02119, USA.
¹² Department of Psychiatry and Behavioral Science, Medical University of South Carolina, 67 President St., MSC 861, Charleston, SC 29425, USA.
¹³ Department of Pediatrics, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Boston, MA 02118, USA.
¹⁴ Center for the Clinical Trials Network, National Institute on Drug Abuse, 6001 Executive Blvd, Bethesda, MD 20892, USA.

PMID: 32353544
PMCID: PMC7184985
DOI: 10.1016/j.cct.2020.106014

Multicenter Study

Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations

Theresa Winhusen et al. Contemp Clin Trials. 2020 Jun.

. 2020 Jun:93:106014.

doi: 10.1016/j.cct.2020.106014. Epub 2020 Apr 27.

Authors

Affiliations

¹ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA; Center for Addiction Research, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA. Electronic address: winhusen@carc.uc.edu.
² Departments of Behavioral Science and Psychiatry, University of Kentucky College of Medicine, Center on Drug and Alcohol Research, 845 Angliana Avenue, Lexington, KY 40508, USA.
³ UNC Horizons and Department of Obstetrics and Gynecology, University of North Carolina Chapel Hill, 410 North Greensboro St., Carrboro, NC 27510, USA.
⁴ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA; Center for Addiction Research, University of Cincinnati College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA.
⁵ The Emmes Company, LLC, 401 N Washington Street, Suite 700, Rockville, MD 20850, USA.
⁶ Division of General Academic Pediatrics, MassGeneral Hospital for Children, 125 Nashua St Suite 860, Boston, MA 02114, USA.
⁷ Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Avenue, Cincinnati, OH 45229, USA.
⁸ Department of Healthcare Policy & Research, Weill Cornell Medical College, 425 East 61st Street Suite 301, New York, NY 10065, USA.
⁹ Department of Psychiatry, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Division of Alcohol, Drug and Addictions and the Division of Women's Mental Health, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
¹⁰ Friends Research Institute,1040 Park Ave Suite 103, Baltimore, MD 21201, USA.
¹¹ Department of Pediatrics, Boston Medical Center, 801 Albany Street, Boston, MA 02119, USA.
¹² Department of Psychiatry and Behavioral Science, Medical University of South Carolina, 67 President St., MSC 861, Charleston, SC 29425, USA.
¹³ Department of Pediatrics, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Boston, MA 02118, USA.
¹⁴ Center for the Clinical Trials Network, National Institute on Drug Abuse, 6001 Executive Blvd, Bethesda, MD 20892, USA.

PMID: 32353544
PMCID: PMC7184985
DOI: 10.1016/j.cct.2020.106014

Abstract

Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6-30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.

Keywords: Buprenorphine; Extended-release; Infant; Neurodevelopment; Opioid; Pregnant.

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Conflict of interest statement

Declaration of Competing Interest Dr. Lofwall reported receiving research funding from Braeburn Pharmaceuticals, Inc., consulting fees from Braeburn Pharmaceuticals, Inc. and Titan, and honorarium/travel expenses from Camurus. Dr. Murphy reports having consulted for Sandoz Inc. for work unrelated to the investigation reported here. Dr. Wexelblatt reported receiving consulting fees from Braeburn Pharmaceuticals, Inc. All other authors have no potential conflicts of interest to report.

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References

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Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations

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Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations

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