Opioid Dependence Treatment Therapies in Pregnancy

November 5, 2020 updated by: Elizabeth Krans, MD, University of Pittsburgh

A Pilot Randomized Comparative Effectiveness Clinical Trial of Buprenorphine vs. Methadone for the Treatment of Opioid Dependence in Pregnancy.

The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to 5.8 per 1,000 hospital births per year.1 While methadone is the current, standard treatment for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative. In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS) compared to methadone. However, buprenorphine was also associated with greater study discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone. Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing any short-term improvement in neonatal outcomes. Therefore, The goal of this K23 proposal is to conduct a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant women.

A pilot study is critical to develop the outcome measures, assessment tools and participant tracking techniques necessary for a future, large-scale comparative effectiveness clinical trial. An examination of feasibility and acceptability will also allow use to characterize the subpopulations of OD pregnant women willing to participate in treatment randomization, identify patient and provider characteristics associated with established treatment preferences and inform the development of strategies to improve participation and enhance the generalizability of the future large-scale clinical trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objective:

The goal of this proposal is to conduct a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of opioid dependent pregnant women.

Specific Aims:

Aim 1: Evaluate the feasibility of conducting a randomized study comparing office-based buprenorphine vs. federally licensed methadone programs for the treatment of OD pregnant women. OD pregnant women (n=50) will be randomized (1:1) to office-based buprenorphine vs. a federally licensed methadone program. Feasibility will be assessed by measuring the proportion of OD pregnant women who are eligible, who enroll, who remain in the study and by the ability to monitor treatment program factors (e.g. compliance with treatment provider/facility visits, counseling sessions, prenatal care visits, social services involvement) and maternal treatment outcomes such as treatment retention, illicit drug use and HIV risk behavior.

Aim 2: Describe the perspectives of OD pregnant women and their providers regarding buprenorphine vs. methadone for the treatment of opioid dependence in pregnancy. Study acceptability will be assessed by conducting qualitative semi-structured interviews with three groups: (1) pilot participants to determine their satisfaction with the assigned treatment program and identify mismatches between treatment program services and participants' needs; (2) prenatal care and opioid treatment providers to identify ways to improve the treatment process in pregnancy and to suggest ideas for care coordination; (3) OD pregnant women who are ineligible or who choose not to participate in the pilot trial will also be asked to participate in an interview to gain a broader perspective of attitudes and perspectives regarding opioid treatment programs in pregnancy.

Aim 3: Identify barriers and facilitators to treatment retention in the postpartum period and identify key functional outcomes relevant to reductions in illicit drug use during pregnancy. Illicit drug use relapse is most common in the immediate postpartum period when stresses associated with motherhood are the greatest. Therefore, pilot participants will be followed at 3, 6, 9 and 12 weeks postpartum to identify barriers and facilitators specific to the postpartum period that may impact treatment retention. The relationship between postpartum treatment retention and maternal functional outcomes will also be explored (e.g. breastfeeding, postpartum depression, motherhood satisfaction, infant custody, employment, and criminality).

Background:

The incidence of opioid dependence in pregnancy increased over the last decade from 1.2 to 5.8 per 1,000 hospital births per year. While methadone is the current, standard treatment for opioid dependent (OD) pregnant women, buprenorphine recently emerged as an alternative. In a recent clinical trial (MOTHER), buprenorphine was associated with superior neonatal outcomes such as shorter duration of treatment for neonatal abstinence syndrome (NAS) compared to methadone. However, buprenorphine was also associated with greater study discontinuation (33% vs. 18%) and illicit opioid use (33% vs. 23%) compared to methadone. Treatment dropout often leads to relapse and resumption of high-risk behaviors, overshadowing any short-term improvement in neonatal outcomes. Therefore, the next research question that emerges is which is the most effective treatment (buprenorphine vs. methadone) for a particular patient during pregnancy?

In clinical settings, differences in maternal characteristics, treatment program structure and patient and provider preferences may surpass the impact of pharmacology on maternal treatment outcomes (treatment retention, illicit drug use, HIV risk behavior). Buprenorphine is dispensed in office-based settings by a variety of providers and with less regulatory oversight than methadone. Methadone is dispensed from federally licensed facilities that often incorporate counseling and support services into treatment protocols. Successful office-based treatment relies on shared power and responsibility, close patient-provider relationships and careful attention to psychosocial co-morbidities. Failure to match patient problem severity to differences in treatment program structure may contribute to adverse maternal outcomes. Therefore, to understand the comparative effectiveness of buprenorphine vs. methadone in pregnancy, the impact of patient problem severity and treatment program structure on maternal (vs. neonatal) outcomes must be compared.

Significance:

Findings from this project will provide the preliminary data to support a comparative effectiveness clinical trial designed to compare the impact of office-based buprenorphine vs. federally licensed methadone programs on maternal treatment and postpartum functional outcomes in OD women. The ultimate goal of this line of research is develop evidence-based clinical guidelines to guide provider decision-making regarding the most effective treatment (buprenorphine vs. methadone) for a particular patient during pregnancy.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee-Womens Hospital of UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women 18+ years old, with a singleton pregnancy ≤ 28 weeks gestation confirmed by ultrasound, who meet Diagnostic and Statistical Manual-IV criteria for opioid dependence confirmed by urine drug screen (UDS), who are interested in opioid maintenance treatment and plan to receive prenatal care and deliver at Magee Womens Hospital (MWH) will be recruited.

Exclusion Criteria:

  • (1) active, current dependence on benzodiazepines or alcohol
  • (2) acute severe psychiatric condition in need of immediate treatment (e.g. suicidal ideations)
  • (3) pending or legal action that could prohibit or interfere with participation (e.g. incarceration)
  • (4) current, established treatment with methadone or buprenorphine. Exclusion criteria are based on the Substance Abuse and Mental Health Services Administration (SAMHSA) recommendations for office-based buprenorphine use.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Buprenorphine Maintenance Treatment
Buprenorphine Maintenance Treatment patients will receive instructions regarding a follow-up, outpatient appointment with the Pregnancy Recovery Center at Magee-Womens Hospital, which specializes in Opioid maintenance treatment for pregnant patients, for the next day following enrollment in the study for induction onto buprenorphine maintenance treatment.
Drug: Buprenorphine
This is a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone treatment programs for OD pregnant women.
Other: Methadone Maintenance Treatment
Methadone Maintenance Treatment patients will be immediately admitted to Magee-Womens Hospital for an inpatient induction onto methadone maintenance treatment.
Drug: Methadone
This is a pilot study to establish the feasibility and acceptability of a randomized comparative effectiveness clinical trial comparing office-based buprenorphine vs. federally licensed methadone treatment programs for OD pregnant women.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who are recruited, enrolled, retained, and who complete the study.
Time Frame: 12 Months
evaluate a minimum of 9 OD pregnant women per month for possible participation and enrollment, randomize a minimum of 4 participants per month to office-based buprenorphine (PRC) or methadone treatment facility (NATP) for a total of 50 participants over a 12 month enrollment period, retain ≥ 80% of randomized participants until 12 weeks postpartum, and maintain < 5% of incomplete data.
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Elizabeth E Krans, MD, MSc, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 20, 2017

Primary Completion (Actual)

October 9, 2019

Study Completion (Actual)

October 5, 2020

Study Registration Dates

First Submitted

October 24, 2016

First Submitted That Met QC Criteria

March 27, 2017

First Posted (Actual)

March 31, 2017

Study Record Updates

Last Update Posted (Actual)

November 9, 2020

Last Update Submitted That Met QC Criteria

November 5, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO16020403
  • 1K23DA038789-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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