Treatment of Neonatal Abstinence Syndrome: Evaluation of Efficacy of Phenobarbital in Combination With Either Methadone or Diluted Deodorized Tincture of Opium as Stabilizing and Tapering Regiments
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Length of Treatment With Opioid Medication
研究概览
简要总结
This study compares treatment of Neonatal Abstinence Syndrome (NAS) with two different drugs for the difference in the length of treatment. This is a randomized, open-label comparison of phenobarbital and methadone versus phenobarbital and diluted deodorized tincture of opium (dDTO) where phenobarbital is the initial drug used to stabilize neonatal withdrawal.
详细描述
a.Procedures: NAS scoring is currently done on infants meeting the inclusion criteria [IDD 29:070]. NAS scores are initially done every 2 hours for 24 hours and then every 4 hours when awake or before feeding for the duration of observation or treatment.
i. NAS scores may indicate more than withdrawal. Conditions such as colic, reflux, or baseline irritability may influence the baseline scores. Decisions made based on the NAS scores should take into account these factors and the baseline for the infant.
b.Emergence of symptom, dosing, and initiation of treatment: Withdrawal is defined as at least 2 NAS scores >8 or 1 NAS score >12. Once withdrawal has emerged, the infant will be given: i. Phenobarbital 20 to 30 mg/kg to load divided in up to 3 doses over 24 hours and maintenance phenobarbital should be started at 2.5 mg/kg/dose administered Q 12h, 12 hours after the loading dose is ended. NAS scoring is continued and if scores remain <8 for a minimum of 5 days after starting phenobarbital, the infant is eligible for discharge.
ii. If after phenobarbital treatment has been started, at least 2 NAS scores >8 or 1 NAS score >12, then a phenobarbital level will be drawn and a mini-load calculated to reach a level of 30 mg/dl. If withdrawal is not controlled or re-emerges after the mini-load dose, the infant will be randomized to one of the two arms of the study - methadone or dDTO.
iii. Twins will be randomized together to the same arm. iv. Randomization will be stratified into mothers on narcotic treatment >3 months and those not in treatment or <3 months. Randomization will be done in blocks of 10 for each stratum.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 6 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of opioid withdrawal clinically as defined by 2 NAS scores >8 or 1 NAS score >12 over a 4 to 8 hour time period, AND
- •Gestation >=35 weeks at entry defined by best obstetrical and physical exam criteria, AND
- •Medically stable condition, other than in opioid withdrawal, in the opinion of the attending neonatologist, AND EITHER,
- •Meconium or urine drug screen positive for opioids on mother or newborn, OR
- •Known maternal prescription of opioids for chronic pain management during at least the last trimester of pregnancy, OR
- •Known maternal prescription of opioids for treatment of addiction, OR
- •Suspected or admitted abuse with opioid drugs
- •Infants of mothers with a medical or psychiatric diagnosis will not be excluded, unless the maternal diagnosis precludes informed consent
排除标准
- •Gestation <35 weeks at entry defined by best obstetrical and physical exam criteria.
- •Hypoglycemia, hypomagnesaemia, or hypocalcaemia until corrected.
- •Serious medical illness such as sepsis, pneumonia, hyperthyroidism, meningitis, intracranial hemorrhage, perinatal depression, or respiratory failure requiring admission to the NICU.
- •Evidence of major congenital anomalies or genetic syndromes that impact the neonatal course.
研究组 & 干预措施
1 (Phenobarbital and Methadone)
The following is a dosing guide for methadone:
- The neonatal concentration is 1 mg/ml of methadone. It is administered orally every 12 hours.
- For the first 24 hours, doses will be prescribed every 6 hours using a sliding scale in response to the last NAS score:
NAS Score Methadone dose 8-11 0.05 mg/kg/dose 12-15 0.1 mg/kg/dose
≥16 0.15 mg/kg/dose 3. Maximum dose of methadone will be 0.15 mg/kg/dose. 4. After the first 24 hours of treatment, the total methadone dose will be summed and that dose divided into two doses, given 12 hours apart. For the following 24 hours, additional doses may be given every 6 hours as needed and added to the next 24 hour's doses divided every 12 hours, until NAS scores are consistently <8 for 48 hours. 5. If at any pointthe maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the dDTO arm.
干预措施: Methadone (Drug)
2 (Phenobarbital and Diluted Deodorized Tincture of Opium)
The following is a dosing guide for dDTO:
- The neonatal concentration is 1:24 dilution for a concentration of 0.4%, equivalent to 0.4 mg/ml of morphine. It is administered orally every 4 hours.
- The starting dose will be determined using a sliding scale in response to the last NAS score before starting.
NAS Score Starting dDTO dose 8-11 0.4 mg/kg/day 12-15 0.6 mg/kg/day
≥16 0.8 mg/kg/day 3. The maximum dose of DTO will be 0.8 mg/kg/day. 4. After the first 24 hours of treatment, if the NAS scores are still ≥8, the dose will be increased to the next level. 5. If at any point the maximum dose of methadone is reached and withdrawal is not controlled, then in the opinion of two neonatologists the patient can be crossed-over to the methadone arm.
干预措施: Diluted Deodorized Tincture of Opium (Drug)
结局指标
主要结局
Length of Treatment With Opioid Medication
时间窗: Up to 12 months
Up to 12 months
次要结局
未报告次要终点
研究者
Mark S Brown, MD
Chief of Pediatric Service, Neonatalogy
Eastern Maine Medical Center