Buprenorphine vs Buprenorphine/Naloxone on the Effects of Maternal Symptomatology

Opioid-use Disorder Clinical Trial

Official title:

Comparison of Buprenorphine vs Buprenorphine/Naloxone on the Effects of Maternal Symptomatology

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03740243
• Other study ID #: 1175806
• Status: Withdrawn
• Phase: Phase 4
• Start date: November 30, 2018
• Est. completion date: March 22, 2020

Study information

• Verified date: March 2020
• Source: Stony Brook University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

Buprenorphine and Buprenorphine/naloxone each are used to treat opioid use disorders in pregnancy.

Buprenorphine has many preferential characteristics over methadone including decreased risk of maternal overdose, lower incidence of preterm labor, less frequent clinical visits, shorter duration of neonatal hospital stay and treatment for neonatal abstinence syndrome. Recent studies have found that increasing the dosing frequencies of buprenorphine is more efficacious to prevent maternal withdrawal symptoms, improve compliance, and theoretically produce better pregnancy outcomes.

Buprenorphine/naloxone, a combination opioid of buprenorphine and naloxone, has also been investigated as an alternative to treatment and maintenance for opioid use disorder. The advantage of the combination of buprenorphine with naloxone is that it reduces the potential for abuse. As a partial mu opioid agonist, buprenorphine alone has the capacity to induce typical opioid effects such as euphoria, which are enhanced when the drug is taken intravenously. By combining buprenorphine with naloxone, an opioid antagonist, the capacity for buprenorphine to be abused is reduced.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 22, 2020
• Est. primary completion date: March 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 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

Exclusion Criteria:

• Known or suspected allergy to buprenorphine or buprenorphine/naloxone

• Carrying a fetus with known aneuploidy or anomaly

Related Conditions & MeSH terms

• Opioid-use Disorder
• Substance-Related Disorders

Intervention

Drug:
• Buprenorphine/naloxone
Buprenorphine/naloxone tablet or film
• Buprenorphine
Buprenorphine tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Stony Brook University

References & Publications (15)

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: 1 — View Citation

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: 10.1 — View Citation

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- — View Citation

Committee on Obstetric Practice. 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. — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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-2016-011 — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. English, French. — View Citation

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. — View Citation

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. — View Citation

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):363-8. doi: 10.1097/AOG.0000000000000640. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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)
Primary	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	Maternal Outcomes Withdraw Scoring	Prenatal Clinical Opioid Withdraw Scale (COWS) score and drug cravings score (0 to 48 score); Score interpretation: 5-12 = Mild 13-24 = Moderate 25-36 = Moderately Severe More than 36 = Severe Withdrawal	Duration of pregnancy and 2 months of postpartum period
Secondary	Maternal Outcome Metabolites	Umbilical cord blood levels of metabolites of buprenorphine (norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide) which are obtained from the umbilical cord after delivery of the baby (one time specimen for evaluation)	At delivery of newborn
Secondary	Placental dysmaturity	Placental histology (obtained at delivery - pathology specimen)	At delivery of newborn
Secondary	Neonatal Outcomes	Neonatal Abstinence Syndrome (NAS) rate	Birth until discharge from hospital (performed during hospitalization of newborn from 0 to 30 days of life)
Secondary	Neonatal stay	Duration of newborn inpatient hospital stay	Birth to newborn discharge home (from day 0 through 120 days of life)
Secondary	Newborn	Gestational age at birth (range 23 to 43 weeks)	At birth