RCT Comparing Methadone and Buprenorphine in Pregnant Women
2015年7月30日 更新者：Hendree E. Jones、Johns Hopkins University
Maternal Opioid Treatment: Human Experimental Research
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.
研究概览
详细说明
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.
研究类型
介入性
注册 (实际的)
175
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Ontario
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Toronto、Ontario、加拿大、M6R 1B5
- St. Joseph's Health Centre
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Vienna、奥地利、A1090
- Medical University of Vienna
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Maryland
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Baltimore、Maryland、美国、21224
- Johns Hopkins University School of Medicine
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Michigan
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Detroit、Michigan、美国、48207
- Wayne State University
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19107
- Thomas Jefferson University
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Rhode Island
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Providence、Rhode Island、美国、02912
- Brown University
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Tennessee
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Nashville、Tennessee、美国、37232
- Vanderbilt University
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Vermont
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Burlington、Vermont、美国、05401
- University of Vermont
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 41年 (成人)
接受健康志愿者
不
有资格学习的性别
女性
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：丁丙诺啡
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sl daily 2-32 mg
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有源比较器：Methadone
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daily oral dosing 20-140 mg
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Child's Head Circumference Measurement (Measured at Birth)
大体时间：birth
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birth
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Child's Length of Hospital Stay
大体时间：delivery until hospital discharge (min=2 days, max=79 days)
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delivery until hospital discharge (min=2 days, max=79 days)
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Number of Children Requiring Treatment for Neonatal Abstinence Signs (NAS)
大体时间：From birth until hospital discharge (min=4 days, max=10, depending on site)
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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.
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From birth until hospital discharge (min=4 days, max=10, depending on site)
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Child's Peak Daily Total NAS Score
大体时间：minimum twice daily from birth until NAS no longer measured (min=10 days)
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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.
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minimum twice daily from birth until NAS no longer measured (min=10 days)
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Total Amount of Morphine Sulfate That a Neonate Receives to Treat NAS
大体时间：Start of NAS treatment until discontinuation of NAS treatment (min=0 days, max=76 days)
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Total amount in mg
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Start of NAS treatment until discontinuation of NAS treatment (min=0 days, max=76 days)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Mother's Self-report of Drug Use (Measured Monthly by Time Line Follow Back)
大体时间：monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)
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monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)
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Mother's HIV Risk Behaviors (Measured Monthly by Risk Behavior Assessment)
大体时间：monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)
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monthly from study entry until discontinuation or delivery (min=29 days, max=239 days)
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Mother's Measures of Dose Adequacy and Acceptance Over Time (Measured Weekly by Dose Adequacy Measure)
大体时间：from study entry until discontinuation or delivery (min=29 days, max=239 days)
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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.
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from study entry until discontinuation or delivery (min=29 days, max=239 days)
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Mother's Psychosocial Functioning at Delivery as Measured by the Addiction Severity Index Psychosocial Index Score
大体时间：at delivery
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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.
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at delivery
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Hendree E. Jones, PhD、Johns Hopkins University
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2005年7月1日
初级完成 (实际的)
2009年8月1日
研究完成 (实际的)
2010年6月1日
研究注册日期
首次提交
2005年12月28日
首先提交符合 QC 标准的
2005年12月28日
首次发布 (估计)
2005年12月30日
研究记录更新
最后更新发布 (估计)
2015年8月5日
上次提交的符合 QC 标准的更新
2015年7月30日
最后验证
2015年7月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.