RCT Comparing Methadone and Buprenorphine in Pregnant Women

NCT ID: NCT00271219

Last Updated: 2015-08-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2010-06-30

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.

Conditions

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Opioid Related Disorders Pregnancy Opioid Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Buprenorphine

Buprenorphine

Group Type EXPERIMENTAL

Buprenorphine

Intervention Type DRUG

sl daily 2-32 mg

Methadone

Methadone

Group Type ACTIVE_COMPARATOR

Methadone

Intervention Type DRUG

daily oral dosing 20-140 mg

Interventions

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Methadone

daily oral dosing 20-140 mg

Intervention Type DRUG

Buprenorphine

sl daily 2-32 mg

Intervention Type DRUG

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

41 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Hendree E. Jones

Professor, Dept of Psychiatry and Behavioral Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hendree E. Jones, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Brown University

Providence, Rhode Island, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

University of Vermont

Burlington, Vermont, United States

Site Status

Medical University of Vienna

Vienna, , Austria

Site Status

St. Joseph's Health Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Austria Canada

References

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Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR. Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement. Am J Addict. 2012 Nov;21 Suppl 1:S1-4. doi: 10.1111/j.1521-0391.2012.00289.x.

Reference Type DERIVED
PMID: 23786504 (View on PubMed)

Holbrook AM, Jones HE, Heil SH, Martin PR, Stine SM, Fischer G, Coyle MG, Kaltenbach K. Induction of pregnant women onto opioid-agonist maintenance medication: an analysis of withdrawal symptoms and study retention. Drug Alcohol Depend. 2013 Sep 1;132(1-2):329-34. doi: 10.1016/j.drugalcdep.2013.02.031. Epub 2013 Mar 21.

Reference Type DERIVED
PMID: 23523131 (View on PubMed)

Jones HE, Heil SH, Tuten M, Chisolm MS, Foster JM, O'Grady KE, Kaltenbach K. Cigarette smoking in opioid-dependent pregnant women: neonatal and maternal outcomes. Drug Alcohol Depend. 2013 Aug 1;131(3):271-7. doi: 10.1016/j.drugalcdep.2012.11.019. Epub 2012 Dec 29.

Reference Type DERIVED
PMID: 23279924 (View on PubMed)

McNicholas LF, Holbrook AM, O'Grady KE, Jones HE, Coyle MG, Martin PR, Heil SH, Stine SM, Kaltenbach K. Effect of hepatitis C virus status on liver enzymes in opioid-dependent pregnant women maintained on opioid-agonist medication. Addiction. 2012 Nov;107 Suppl 1(0 1):91-7. doi: 10.1111/j.1360-0443.2012.04043.x.

Reference Type DERIVED
PMID: 23106931 (View on PubMed)

Holbrook AM, Baxter JK, Jones HE, Heil SH, Coyle MG, Martin PR, Stine SM, Kaltenbach K. Infections and obstetric outcomes in opioid-dependent pregnant women maintained on methadone or buprenorphine. Addiction. 2012 Nov;107 Suppl 1(Suppl 1):83-90. doi: 10.1111/j.1360-0443.2012.04042.x.

Reference Type DERIVED
PMID: 23106930 (View on PubMed)

Benningfield MM, Dietrich MS, Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Fischer G, Martin PR. Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes. Addiction. 2012 Nov;107 Suppl 1(0 1):74-82. doi: 10.1111/j.1360-0443.2012.04041.x.

Reference Type DERIVED
PMID: 23106929 (View on PubMed)

Coyle MG, Salisbury AL, Lester BM, Jones HE, Lin H, Graf-Rohrmeister K, Fischer G. Neonatal neurobehavior effects following buprenorphine versus methadone exposure. Addiction. 2012 Nov;107 Suppl 1(0 1):63-73. doi: 10.1111/j.1360-0443.2012.04040.x.

Reference Type DERIVED
PMID: 23106928 (View on PubMed)

Gaalema DE, Scott TL, Heil SH, Coyle MG, Kaltenbach K, Badger GJ, Arria AM, Stine SM, Martin PR, Jones HE. Differences in the profile of neonatal abstinence syndrome signs in methadone- versus buprenorphine-exposed neonates. Addiction. 2012 Nov;107 Suppl 1(0 1):53-62. doi: 10.1111/j.1360-0443.2012.04039.x.

Reference Type DERIVED
PMID: 23106927 (View on PubMed)

Kaltenbach K, Holbrook AM, Coyle MG, Heil SH, Salisbury AL, Stine SM, Martin PR, Jones HE. Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication. Addiction. 2012 Nov;107 Suppl 1(0 1):45-52. doi: 10.1111/j.1360-0443.2012.04038.x.

Reference Type DERIVED
PMID: 23106926 (View on PubMed)

Salisbury AL, Coyle MG, O'Grady KE, Heil SH, Martin PR, Stine SM, Kaltenbach K, Weninger M, Jones HE. Fetal assessment before and after dosing with buprenorphine or methadone. Addiction. 2012 Nov;107 Suppl 1(0 1):36-44. doi: 10.1111/j.1360-0443.2012.04037.x.

Reference Type DERIVED
PMID: 23106925 (View on PubMed)

Jones HE, Fischer G, Heil SH, Kaltenbach K, Martin PR, Coyle MG, Selby P, Stine SM, O'Grady KE, Arria AM. Maternal Opioid Treatment: Human Experimental Research (MOTHER)--approach, issues and lessons learned. Addiction. 2012 Nov;107 Suppl 1(0 1):28-35. doi: 10.1111/j.1360-0443.2012.04036.x.

Reference Type DERIVED
PMID: 23106924 (View on PubMed)

Jones HE, Heil SH, Baewert A, Arria AM, Kaltenbach K, Martin PR, Coyle MG, Selby P, Stine SM, Fischer G. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review. Addiction. 2012 Nov;107 Suppl 1(0 1):5-27. doi: 10.1111/j.1360-0443.2012.04035.x.

Reference Type DERIVED
PMID: 23106923 (View on PubMed)

Unger A, Jagsch R, Bawert A, Winklbaur B, Rohrmeister K, Martin PR, Coyle M, Fischer G. Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates? Gend Med. 2011 Dec;8(6):355-64. doi: 10.1016/j.genm.2011.10.001. Epub 2011 Nov 15.

Reference Type DERIVED
PMID: 22088886 (View on PubMed)

Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010 Dec 9;363(24):2320-31. doi: 10.1056/NEJMoa1005359.

Reference Type DERIVED
PMID: 21142534 (View on PubMed)

Other Identifiers

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R01DA015764

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01DA15764-1

Identifier Type: -

Identifier Source: secondary_id

DPMC

Identifier Type: -

Identifier Source: secondary_id

R01DA15764-1

Identifier Type: -

Identifier Source: org_study_id

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