RCT Comparing Methadone and Buprenorphine in Pregnant Women

Study Overview
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Brief Summary
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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
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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.

Official Title
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Maternal Opioid Treatment: Human Experimental Research

Conditions
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Opioid Related Disorders, Pregnancy, Opioid Dependence

Intervention / Treatment
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* Drug: Methadone
* Drug: Buprenorphine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Buprenorphine<br>Buprenorphine | Drug: Buprenorphine<br>* sl daily 2-32 mg<br>|
| Active Comparator: Methadone<br>Methadone | Drug: Methadone<br>* daily oral dosing 20-140 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | From birth until hospital discharge (min=4 days, max=10, depending on site) | 
| Child's Peak Daily Total NAS Score | 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. | minimum twice daily from birth until NAS no longer measured (min=10 days) | 
| Total Amount of Morphine Sulfate That a Neonate Receives to Treat NAS | Total amount in mg | Start of NAS treatment until discontinuation of NAS treatment (min=0 days, max=76 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | from study entry until discontinuation or delivery (min=29 days, max=239 days) | 
| Mother's Psychosocial Functioning at Delivery as Measured by the Addiction Severity Index Psychosocial Index Score | 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. | at delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opiate addiction, opiate dependence, substance abuse, addiction, substance addiction, pregnancy, buprenorphine, methadone, fetal, neonatal, post-partum