Buprenorphine vs Buprenorphine/Naloxone on the Effects of Maternal Symptomatology

NCT03740243 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: 1175806
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assesses the efficacy of buprenorphine/naloxone vs buprenorphine on maternal withdrawal symptoms and drug cravings. This is a randomized controlled trial to a cohort of pregnant women seeking medication-assisted treatment for opioid use disorders. Half of participants will receive buprenorphine, while the other half of participants receive a combination of buprenorphine/naloxone

Conditions

Opioid-use Disorder

Keywords

opioid use disorder; Buprenorphine/naloxone; Buprenorphine

Outcome Measures

Primary Outcomes (4)

• Compliance antepartum

  To compare compliance with buprenorphine versus buprenorphine/naloxone medication-assisted treatment (MAT) in pregnant women. Compliance will include the incidence of urine toxicology testing positive for illicit substances during prenatal care and at the time of admission for delivery.

  From entry into the study until delivery (through study completion, an average of 9 months which is duration of the pregnancy)

• Compliance postpartum

  To compare compliance with buprenorphine versus buprenorphine/naloxone medication-assisted treatment (MAT) in the postpartum period. Compliance will include the incidence of urine toxicology testing positive for illicit substances from the time of discharge from the hospital following the delivery over a 2 month period postpartum (postpartum period).

  2 month period postpartum

• Dosing antepartum

  Evaluate all women for the need a significant dosing change in buprenorphine or buprenorphine/naloxone (\>50% increase or decrease) during pregnancy.

  From entry into the study until delivery (through study completion, an average of 9 months which is duration of the pregnancy)

• Dosing postpartum

  Evaluate all women for the need a significant dosing change in buprenorphine or buprenorphine/naloxone (\>50% increase or decrease) from the hospital following the delivery over a 2 month period postpartum (postpartum period).

  2 month period postpartum

Secondary Outcomes (6)

• Maternal Outcomes Withdraw Scoring

  Duration of pregnancy and 2 months of postpartum period

• Maternal Outcome Metabolites

  At delivery of newborn

• Placental dysmaturity

  At delivery of newborn

• Neonatal Outcomes

  Birth until discharge from hospital (performed during hospitalization of newborn from 0 to 30 days of life)

• Neonatal stay

  Birth to newborn discharge home (from day 0 through 120 days of life)

Study Arms (2)

buprenorphine

ACTIVE COMPARATOR

Buprenorphine 2 mg to 8 mg daily: Light to moderate history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 5-24 Buprenorphine 8 mg to 16 mg daily: Heavy history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 25-36+

Drug: Buprenorphine

buprenorphine/naloxone

EXPERIMENTAL

Buprenorphine/naloxone 4 mg/1 mg daily once daily or twice daily (BID): Light to moderate history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 5-24 Buprenorphine/naloxone 8 mg/2 mg daily once daily or twice daily (BID): Heavy history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 25-36+

Drug: Buprenorphine/naloxone

Interventions

Buprenorphine/naloxone DRUG

Buprenorphine/naloxone tablet or film

Also known as: suboxone, bunavail, zubsolv

buprenorphine/naloxone

Buprenorphine DRUG

Buprenorphine tablet

Also known as: subutex, belbuca, butrans,sublocade

buprenorphine

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: As this study pertains only to pregnant patients seeking treatment for opioid use disorders, females are the only biologically plausiable participants.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and older
• With a confirmed viable intrauterine pregnancy
• Opioid Use Disorder
• Care in a Stony Brook Medicine OBGYN clinical office sites
• Medication-assisted treatment through Stony Brook Medicine OBGYN office sites

You may not qualify if:

• Known or suspected allergy to buprenorphine or buprenorphine/naloxone
• Carrying a fetus with known aneuploidy or anomaly

Sponsors & Collaborators

• Stony Brook University: lead

Related Publications (15)

• Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstet Gynecol. 2017 Aug;130(2):e81-e94. doi: 10.1097/AOG.0000000000002235.

  PMID: 28742676 RESULT

• Bastian JR, Chen H, Zhang H, Rothenberger S, Tarter R, English D, Venkataramanan R, Caritis SN. Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy. Am J Obstet Gynecol. 2017 Jan;216(1):64.e1-64.e7. doi: 10.1016/j.ajog.2016.09.095. Epub 2016 Sep 26.

  PMID: 27687214 RESULT

• Caritis SN, Bastian JR, Zhang H, Kalluri H, English D, England M, Bobby S, Venkataramanan R. An evidence-based recommendation to increase the dosing frequency of buprenorphine during pregnancy. Am J Obstet Gynecol. 2017 Oct;217(4):459.e1-459.e6. doi: 10.1016/j.ajog.2017.06.029. Epub 2017 Jun 29.

  PMID: 28669739 RESULT

• Chavan NR, Ashford KB, Wiggins AT, Lofwall MR, Critchfield AS. Buprenorphine for Medication-Assisted Treatment of Opioid Use Disorder in Pregnancy: Relationship to Neonatal Opioid Withdrawal Syndrome. AJP Rep. 2017 Oct;7(4):e215-e222. doi: 10.1055/s-0037-1608783. Epub 2017 Dec 7.

  PMID: 29226017 RESULT

• Debelak K, Morrone WR, O'Grady KE, Jones HE. Buprenorphine + naloxone in the treatment of opioid dependence during pregnancy-initial patient care and outcome data. Am J Addict. 2013 May-Jun;22(3):252-4. doi: 10.1111/j.1521-0391.2012.12005.x.

  PMID: 23617867 RESULT

• Geber WF, Schramm LC. Congenital malformations of the central nervous system produced by narcotic analgesics in the hamster. Am J Obstet Gynecol. 1975 Dec 1;123(7):705-13. doi: 10.1016/0002-9378(75)90492-5.

  PMID: 907 RESULT

• Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, Collins J, Raisch D, Casadonte P, Goldsmith RJ, Ling W, Malkerneker U, McNicholas L, Renner J, Stine S, Tusel D; Buprenorphine/Naloxone Collaborative Study Group. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med. 2003 Sep 4;349(10):949-58. doi: 10.1056/NEJMoa022164.

  PMID: 12954743 RESULT

• Jumah NA, Edwards C, Balfour-Boehm J, Loewen K, Dooley J, Gerber Finn L, Kelly L. Observational study of the safety of buprenorphine+naloxone in pregnancy in a rural and remote population. BMJ Open. 2016 Oct 31;6(10):e011774. doi: 10.1136/bmjopen-2016-011774.

  PMID: 27799240 RESULT

• Lund IO, Fischer G, Welle-Strand GK, O'Grady KE, Debelak K, Morrone WR, Jones HE. A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes. Subst Abuse. 2013;7:61-74. doi: 10.4137/SART.S10955. Epub 2013 Mar 14.

  PMID: 23531704 RESULT

• Mendelson J, Jones RT. Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4:1 ratio for treatment? Drug Alcohol Depend. 2003 May 21;70(2 Suppl):S29-37. doi: 10.1016/s0376-8716(03)00057-7.

  PMID: 12738348 RESULT

• Nguyen L, Lander LR, O'Grady KE, Marshalek PJ, Schmidt A, Kelly AK, Jones HE. Treating women with opioid use disorder during pregnancy in Appalachia: Initial neonatal outcomes following buprenorphine + naloxone exposure. Am J Addict. 2018 Mar;27(2):92-96. doi: 10.1111/ajad.12687. Epub 2018 Feb 23.

  PMID: 29473258 RESULT

• Poon S, Pupco A, Koren G, Bozzo P. Safety of the newer class of opioid antagonists in pregnancy. Can Fam Physician. 2014 Jul;60(7):631-2, e348-9.

  PMID: 25022635 RESULT

• Simojoki K, Vorma H, Alho H. A retrospective evaluation of patients switched from buprenorphine (Subutex) to the buprenorphine/naloxone combination (Suboxone). Subst Abuse Treat Prev Policy. 2008 Jun 17;3:16. doi: 10.1186/1747-597X-3-16.

  PMID: 18559110 RESULT

• Strain EC, Harrison JA, Bigelow GE. Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble-films. Clin Pharmacol Ther. 2011 Mar;89(3):443-9. doi: 10.1038/clpt.2010.352. Epub 2011 Jan 26.

  PMID: 21270789 RESULT

• Wiegand SL, Stringer EM, Stuebe AM, Jones H, Seashore C, Thorp J. Buprenorphine and naloxone compared with methadone treatment in pregnancy. Obstet Gynecol. 2015 Feb;125(2):363-368. doi: 10.1097/AOG.0000000000000640.

  PMID: 25569005 RESULT

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination; Buprenorphine; Sublocade

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• David J Garry, DO

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Maternal Fetal Medicine

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: November 14, 2018
• Study Start: November 30, 2018
• Primary Completion: March 22, 2020
• Study Completion: March 22, 2020
• Last Updated: March 24, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share