Buprenorphine vs Buprenorphine/Naloxone on the Effects of Maternal Symptomatology

Study Overview
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Brief Summary
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This study will assesses the efficacy of buprenorphine/naloxone vs buprenorphine on maternal withdrawal symptoms and drug cravings. This is a randomized controlled trial to a cohort of pregnant women seeking medication-assisted treatment for opioid use disorders. Half of participants will receive buprenorphine, while the other half of participants receive a combination of buprenorphine/naloxone

Detailed Description
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Buprenorphine and Buprenorphine/naloxone each are used to treat opioid use disorders in pregnancy. Buprenorphine has many preferential characteristics over methadone including decreased risk of maternal overdose, lower incidence of preterm labor, less frequent clinical visits, shorter duration of neonatal hospital stay and treatment for neonatal abstinence syndrome. Recent studies have found that increasing the dosing frequencies of buprenorphine is more efficacious to prevent maternal withdrawal symptoms, improve compliance, and theoretically produce better pregnancy outcomes. Buprenorphine/naloxone, a combination opioid of buprenorphine and naloxone, has also been investigated as an alternative to treatment and maintenance for opioid use disorder. The advantage of the combination of buprenorphine with naloxone is that it reduces the potential for abuse. As a partial mu opioid agonist, buprenorphine alone has the capacity to induce typical opioid effects such as euphoria, which are enhanced when the drug is taken intravenously. By combining buprenorphine with naloxone, an opioid antagonist, the capacity for buprenorphine to be abused is reduced.

Official Title
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Comparison of Buprenorphine vs Buprenorphine/Naloxone on the Effects of Maternal Symptomatology

Conditions
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Opioid-use Disorder

Intervention / Treatment
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* Drug: Buprenorphine/naloxone
* Drug: Buprenorphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age and older With a confirmed viable intrauterine pregnancy Opioid Use Disorder Care in a Stony Brook Medicine OBGYN clinical office sites Medication-assisted treatment through Stony Brook Medicine OBGYN office sites Exclusion Criteria: Known or suspected allergy to buprenorphine or buprenorphine/naloxone Carrying a fetus with known aneuploidy or anomaly

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: buprenorphine<br>Buprenorphine 2 mg to 8 mg daily: Light to moderate history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 5-24 Buprenorphine 8 mg to 16 mg daily: Heavy history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 25-36+ | Drug: Buprenorphine<br>* Buprenorphine tablet<br>* Other names: subutex, belbuca, butrans,sublocade;|
| Experimental: buprenorphine/naloxone<br>Buprenorphine/naloxone 4 mg/1 mg daily once daily or twice daily (BID): Light to moderate history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 5-24 Buprenorphine/naloxone 8 mg/2 mg daily once daily or twice daily (BID): Heavy history of opioid use (heroin, oxycodone, etc.) and/or Clinical Opioid Withdraw Scale (COWS) scores 25-36+ | Drug: Buprenorphine/naloxone<br>* Buprenorphine/naloxone tablet or film<br>* Other names: suboxone, bunavail, zubsolv;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance antepartum | To compare compliance with buprenorphine versus buprenorphine/naloxone medication-assisted treatment (MAT) in pregnant women. Compliance will include the incidence of urine toxicology testing positive for illicit substances during prenatal care and at the time of admission for delivery. | From entry into the study until delivery (through study completion, an average of 9 months which is duration of the pregnancy) | 
| Compliance postpartum | To compare compliance with buprenorphine versus buprenorphine/naloxone medication-assisted treatment (MAT) in the postpartum period. Compliance will include the incidence of urine toxicology testing positive for illicit substances from the time of discharge from the hospital following the delivery over a 2 month period postpartum (postpartum period). | 2 month period postpartum | 
| Dosing antepartum | Evaluate all women for the need a significant dosing change in buprenorphine or buprenorphine/naloxone (>50% increase or decrease) during pregnancy. | From entry into the study until delivery (through study completion, an average of 9 months which is duration of the pregnancy) | 
| Dosing postpartum | Evaluate all women for the need a significant dosing change in buprenorphine or buprenorphine/naloxone (>50% increase or decrease) from the hospital following the delivery over a 2 month period postpartum (postpartum period). | 2 month period postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal Outcomes Withdraw Scoring | Prenatal Clinical Opioid Withdraw Scale (COWS) score and drug cravings score (0 to 48 score) Score interpretation: 5-12 = Mild 13-24 = Moderate 25-36 = Moderately Severe More than 36 = Severe Withdrawal | Duration of pregnancy and 2 months of postpartum period | 
| Maternal Outcome Metabolites | Umbilical cord blood levels of metabolites of buprenorphine (norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide) which are obtained from the umbilical cord after delivery of the baby (one time specimen for evaluation) | At delivery of newborn | 
| Placental dysmaturity | Placental histology (obtained at delivery - pathology specimen) | At delivery of newborn | 
| Neonatal Outcomes | Neonatal Abstinence Syndrome (NAS) rate | Birth until discharge from hospital (performed during hospitalization of newborn from 0 to 30 days of life) | 
| Neonatal stay | Duration of newborn inpatient hospital stay | Birth to newborn discharge home (from day 0 through 120 days of life) | 
| Newborn | Gestational age at birth (range 23 to 43 weeks) | At birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid use disorder, Buprenorphine/naloxone, Buprenorphine