RCT Comparing Methadone and Buprenorphine in Pregnant Women
30 juli 2015 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
175
Fas
- Fas 3
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Maryland
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Baltimore, Maryland, Förenta staterna, 21224
- Johns Hopkins University School of Medicine
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Michigan
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Detroit, Michigan, Förenta staterna, 48207
- Wayne State University
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Pennsylvania
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Philadelphia, Pennsylvania, Förenta staterna, 19107
- Thomas Jefferson University
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Rhode Island
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Providence, Rhode Island, Förenta staterna, 02912
- Brown University
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Tennessee
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Nashville, Tennessee, Förenta staterna, 37232
- Vanderbilt University
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Vermont
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Burlington, Vermont, Förenta staterna, 05401
- University of Vermont
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Ontario
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Toronto, Ontario, Kanada, M6R 1B5
- St. Joseph's Health Centre
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Vienna, Österrike, A1090
- Medical University of Vienna
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 41 år (Vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Kvinna
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Buprenorfin
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sl daily 2-32 mg
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Aktiv komparator: Methadone
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daily oral dosing 20-140 mg
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Child's Head Circumference Measurement (Measured at Birth)
Tidsram: birth
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birth
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Child's Length of Hospital Stay
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Mother's Self-report of Drug Use (Measured Monthly by Time Line Follow Back)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Hendree E. Jones, PhD, Johns Hopkins University
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 juli 2005
Primärt slutförande (Faktisk)
1 augusti 2009
Avslutad studie (Faktisk)
1 juni 2010
Studieregistreringsdatum
Först inskickad
28 december 2005
Först inskickad som uppfyllde QC-kriterierna
28 december 2005
Första postat (Uppskatta)
30 december 2005
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
5 augusti 2015
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
30 juli 2015
Senast verifierad
1 juli 2015
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Mentala störningar
- Kemiskt inducerade störningar
- Substansrelaterade störningar
- Narkotikarelaterade störningar
- Opioidrelaterade störningar
- Läkemedels fysiologiska effekter
- Depressiva medel i centrala nervsystemet
- Agenter från det perifera nervsystemet
- Analgetika
- Sensoriska systemagenter
- Analgetika, Opioid
- Narkotika
- Narkotiska antagonister
- Andningsorgan
- Hostdämpande medel
- Buprenorfin
- Metadon
Andra studie-ID-nummer
- R01DA15764-1
- DPMC (Annan identifierare: NIDA)
- R01DA015764 (U.S.S. NIH-anslag/kontrakt)
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Graviditet
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King's College Hospital NHS TrustEuropean Association for the Study of the LiverRekryteringCirros, lever | HELLP syndrom | Intrahepatisk kolestas av graviditet | Graviditetssjukdom | AFLP - Acute Fatty Lever of PregnancyStorbritannien