Clinical trial NCT03098407: Opioid Dependence Treatment Therapies in Pregnancy
Official title: A Pilot Randomized Comparative Effectiveness Clinical Trial of Buprenorphine vs. Methadone for the Treatment of Opioid Dependence in Pregnancy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Opioid-Related Disorders
Pregnancy
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2017-03-31
Enrollment: 55
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants who are recruited, enrolled, retained, and who complete the study.
timeFrame: 12 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Elizabeth E Krans, MD, MSc
role: PRINCIPAL_INVESTIGATOR
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