RCT Comparing Methadone and Buprenorphine in Pregnant Women

This study has been completed.
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Hendree E. Jones, Johns Hopkins University
ClinicalTrials.gov Identifier:
First received: December 28, 2005
Last updated: July 30, 2015
Last verified: July 2015
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.

Condition Intervention Phase
Opioid Related Disorders
Opioid Dependence
Drug: Methadone
Drug: Buprenorphine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Maternal Opioid Treatment: Human Experimental Research

Resource links provided by NLM:

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Child's Head Circumference Measurement (Measured at Birth) [ Time Frame: birth ] [ Designated as safety issue: Yes ]
  • Child's Length of Hospital Stay [ Time Frame: delivery until hospital discharge (min=2 days, max=79 days) ] [ Designated as safety issue: Yes ]
  • Number of Children Requiring Treatment for Neonatal Abstinence Signs (NAS) [ Time Frame: From birth until hospital discharge (min=4 days, max=10, depending on site) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: minimum twice daily from birth until NAS no longer measured (min=10 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Start of NAS treatment until discontinuation of NAS treatment (min=0 days, max=76 days) ] [ Designated as safety issue: Yes ]
    Total amount in mg

Secondary Outcome Measures:
  • Mother's Self-report of Drug Use (Measured Monthly by Time Line Follow Back) [ Time Frame: monthly from study entry until discontinuation or delivery (min=29 days, max=239 days) ] [ Designated as safety issue: No ]
  • Mother's HIV Risk Behaviors (Measured Monthly by Risk Behavior Assessment) [ Time Frame: monthly from study entry until discontinuation or delivery (min=29 days, max=239 days) ] [ Designated as safety issue: Yes ]
  • Mother's Measures of Dose Adequacy and Acceptance Over Time (Measured Weekly by Dose Adequacy Measure) [ Time Frame: from study entry until discontinuation or delivery (min=29 days, max=239 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: at delivery ] [ Designated as safety issue: No ]
    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.

Enrollment: 175
Study Start Date: July 2005
Study Completion Date: June 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Buprenorphine
Drug: Buprenorphine
sl daily 2-32 mg
Active Comparator: Methadone
Drug: Methadone
daily oral dosing 20-140 mg

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.


Ages Eligible for Study:   18 Years to 41 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00271219

United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21224
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48207
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02912
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
Medical University of Vienna
Vienna, Austria, A1090
Canada, Ontario
St. Joseph's Health Centre
Toronto, Ontario, Canada, M6R 1B5
Sponsors and Collaborators
Johns Hopkins University
National Institute on Drug Abuse (NIDA)
Principal Investigator: Hendree E. Jones, PhD Johns Hopkins University
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hendree E. Jones, Professor, Dept of Psychiatry and Behavioral Sciences, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00271219     History of Changes
Other Study ID Numbers: R01DA15764-1  R01DA015764  DPMC 
Study First Received: December 28, 2005
Results First Received: March 11, 2013
Last Updated: July 30, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
opiate addiction
opiate dependence
substance abuse
substance addiction

Additional relevant MeSH terms:
Opioid-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Analgesics, Opioid
Antitussive Agents
Central Nervous System Depressants
Narcotic Antagonists
Peripheral Nervous System Agents
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents

ClinicalTrials.gov processed this record on May 26, 2016