RCT Comparing Methadone and Buprenorphine in Pregnant Women

Phase 3

Completed

Conditions: Pregnancy
Opioid Dependence
Opioid Related Disorders

Interventions: Drug: Methadone
Drug: Buprenorphine

Registration Number: NCT00271219

Lead Sponsor: Johns Hopkins University

Brief Summary: Children born to women who abuse drugs have a high risk of being born with birth defects and developmental problems. Methadone is a drug that is commonly used for treating opioid dependence. However, its use by a pregnant woman can cause severe withdrawal symptoms in a newborn because of the prenatal exposure. The purpose of this study is to evaluate the effectiveness of buprenorphine, another drug, versus methadone in reducing withdrawal symptoms in children born to opioid-dependent women.

Detailed Description: Women who use drugs during pregnancy place their unborn children at high risk for being born addicted to drugs. Such children may also be born with birth defects and may experience learning and behavioral problems. Methadone, a synthetic narcotic, is commonly prescribed to treat opioid addiction. It may not be an optimal solution for opioid-dependent pregnant women, however, because a large percentage of children born to women taking methadone experience severe drug withdrawal symptoms at birth that often require medical treatment. Common opioid withdrawal symptoms, described as neonatal abstinence syndrome (NAS) in babies, include tremors, irritability, sleep problems, seizures, dehydration, and fever. Buprenorphine is a medication that has been approved to treat opioid dependence in individuals who are not pregnant but has not been approved for pregnant individuals. Past research has shown that use of buprenorphine in pregnant women results in improved birth outcomes over methadone. The purpose of this study is to evaluate the effectiveness of buprenorphine versus methadone at reducing opioid withdrawal symptoms in babies born to opioid-dependent women.

This study will enroll opioid-dependent pregnant women who are 13 to 30 weeks pregnant and will follow each woman and her child throughout the pregnancy until 6 weeks postpartum. All participants will undergo an initial screening that will last several hours. Participants will then be randomly assigned to receive either methadone or buprenorphine on a daily basis, and will be required to visit the clinic each day to receive their medication. Outcome measurements will be assessed at weekly study visits throughout the pregnancy, and will include drug use, HIV risk behaviors, medication dose adequacy and safety, treatment retention, and psychosocial functioning. Urine samples will be collected 3 times a week, and blood will be drawn throughout the pregnancy for safety monitoring. Outcome measurements related to the baby will include head circumference measurement, length of hospital stay, severity and frequency of withdrawal symptoms, and amount of medication needed to control withdrawal symptoms.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 175

Inclusion Criteria

Current opioid dependence
Current opioid use, as determined by a urine drug test
Pregnant with a single child with a gestational age of 6 to 30 weeks, as determined by a sonogram

Exclusion Criteria

Current medical condition that would make study participation dangerous, as determined by study physician
Diagnosed with an acute, severe psychiatric illness
Current SCID I-E module diagnosis of benzodiazepine or alcohol abuse
Use of alcohol or benzodiazepines in the 30 days prior to study entry, as determined by the Addiction Severity Index
Pending legal action that may prohibit or interfere with study participation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methadone	Methadone	Methadone
Buprenorphine	Buprenorphine	Buprenorphine

Primary Outcome Measures

Name	Time	Method
Child's Head Circumference Measurement (Measured at Birth)	birth
Child's Length of Hospital Stay	delivery until hospital discharge (min=2 days, max=79 days)
Number of Children Requiring Treatment for Neonatal Abstinence Signs (NAS)	From birth until hospital discharge (min=4 days, max=10, depending on site)	Neonatal abstinence syndrome (NAS) characterized by hyperirritability of the central nervous system and dysfunction in the autonomic nervous system, gastrointestinal tract, and respiratory system.11 When left untreated, NAS can result in serious illness (e.g., diarrhea, feeding difficulties, weight loss, and seizures) and death.
Child's Peak Daily Total NAS Score	minimum twice daily from birth until NAS no longer measured (min=10 days)	NAS was measured with the MOTHER NAS scale, which includes 28 items, 19 of which are used for scoring and medication decisions. Scores can range from 0 to 42, with higher scores indicating more severe withdrawal.
Total Amount of Morphine Sulfate That a Neonate Receives to Treat NAS	Start of NAS treatment until discontinuation of NAS treatment (min=0 days, max=76 days)	Total amount in mg

Secondary Outcome Measures

Name	Time	Method
Mother's Self-report of Drug Use (Measured Monthly by Time Line Follow Back)	monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)
Mother's HIV Risk Behaviors (Measured Monthly by Risk Behavior Assessment)	monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)
Mother's Measures of Dose Adequacy and Acceptance Over Time (Measured Weekly by Dose Adequacy Measure)	from study entry until discontinuation or delivery (min=29 days, max=239 days)	Pregnant women maintained on an opioid agonist medication may require upward adjustment to their medication during the course of pregnant. The Dose Adequacy Measure represented a recordation of dosing adjustments during the course of the study.
Mother's Psychosocial Functioning at Delivery as Measured by the Addiction Severity Index Psychosocial Index Score	at delivery	The Addiction Severity Index is a structured clinical interview that assesses problem severity in 7 areas of functioning: alcohol use, drug use, medical, legal, employment, psychosocial, and psychiatric status. Each area of functioning yields a composite scale score between 0 and 1, with higher scores indicating greater problem severity in that area. Only the psychosocial index was examined in this study.

Trial Locations

Locations (8): University of Vermont
🇺🇸
Burlington, Vermont, United States
Johns Hopkins University School of Medicine
🇺🇸
Baltimore, Maryland, United States
Wayne State University
🇺🇸
Detroit, Michigan, United States
Brown University
🇺🇸
Providence, Rhode Island, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
Medical University of Vienna
🇦🇹
Vienna, Austria
St. Joseph's Health Centre
🇨🇦
Toronto, Ontario, Canada
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States