Endeavor to Stop Nausea/Vomiting Associated With Pregnancy (E-SNAP)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- change in Pregnancy Unique Quality of Emesis (PUQE) score
研究概览
简要总结
The primary objective of this proposal is to conduct an early Phase 2 clinical trial to determine the acceptability, dosing, tolerability and safety of mirtazapine for severe nausea and vomiting of pregnancy (sNVP) that is not adequately responsive to current standard treatments. This plan mirrors clinical practice since commonly prescribed antiemetic/ antinauseant drugs will be tested for efficacy before treating with mirtazapine.
详细描述
Translational Research in Maternal and Pediatric Pharmacology and Therapeutics (PAR-20-299) supports research to "enhance the usage of existing drugs or drug repurposing for safer and more effective treatment for pregnant women" for "the early and conceptual stages of these projects. The primary objective of this proposal is to conduct an early Phase 2 clinical trial to determine the acceptability, dosing, tolerability and safety of mirtazapine for severe nausea and vomiting of pregnancy (sNVP) that is not adequately responsive to current standard treatments. This plan mirrors clinical practice since commonly prescribed antiemetic/ antinauseant drugs will be tested for efficacy before treating with mirtazapine.
Mirtazapine is a promising drug to repurpose for sNVP. It has potent anti-emetic properties and is available as an oral disintegrating formulation. It is used off-label to treat NV during cancer chemotherapy, prevent post-surgical nausea and vomiting and for gastroparesis. It is marketed as the serotonin-norepinephrine reuptake inhibitor antidepressant Remeron®. Mirtazapine has multiple receptor effects beyond those involved in reducing depressive symptoms. In cancer and chemotherapy patients, it produces rapid resolution of nausea and vomiting by blocking physiologic inputs that coordinate emesis. It is hypothesized that repurposing mirtazapine for obstetric use overcomes the challenges of traditional pathways to develop new agents because its pharmacokinetics, safety and dosing have been established for general populations of patients and exposure data are available because it is prescribed to pregnant persons with depression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •singleton pregnancy
- •inpatient or outpatient status
- •English speaking
- •obstetrician's evaluation and diagnosis of sNVP or HG
- •tolerance of oral disintegrating tablet at bedtime
- •PUQE score of 10-15; moderate/high or severe
- •refractory sNVP
- •blood pressure range 70-200 / 45-120
- •normal ECG
排除标准
- •allergic or adverse reaction to mirtazapine
- •patient has bipolar disorder
- •subjects with active depression, or history of or current active suicidal ideation or attempt
- •subjects with renal or hepatic impairment
- •substance about in last 6 months
- •use of medicinal or recreational cannabis-derived products in the last 6 months
- •taking MAOIs, strong CYP3A inducers or inhibitors, and SSRIs
研究组 & 干预措施
Mirtazapine Treatment Arm
Subjects will be administered the initial dose of mirtazapine, with dosage progressively increased over the course of the study. The initial dose of mirtazapine is 15 mg tablet, once per day. The dose will be increased weekly as tolerated up to 45 mg per day. The dose will be increased by 15 mg each week if the lower dose is tolerated without significant side effects. That is to say, the subject will take 15 mg/day every day for the first week, 30 mg/day every day for the second week, and 45 mg/day every day for the third week, with the option of the subject continuing the medication for the remainder of the pregnancy. If subjects choose to discontinue the mirtazapine, there will be a tapering regimen: if a patient is taking 45 mg at the end of week 3, they will begin a taper (by week) of 30 to 15 to 7.5 to 0 mg. If they relapse or has discontinuation symptoms, the previous effective dose will be given. They may attempt to taper again with the same approach.
干预措施: Mirtazapine (Drug)
结局指标
主要结局
change in Pregnancy Unique Quality of Emesis (PUQE) score
时间窗: daily for three weeks
We will utilize the PUQE scale to capture the severity of nausea and vomiting in pregnancy based on three physical symptoms: nausea, vomiting, and retching over the previous 24 hours. A PUQE score of \< 6 is considered mild, a score from 7-12 is moderate, and a score of 13+ is considered severe. This scale will be entered daily in REDCap directly by the participant.
次要结局
- Self-Administered Comorbidity Questionnaire (SCQ)(weekly for three weeks)
- 9-Item Patient Health Questionnaire (PHQ-9)(weekly for three weeks)
- Generalized Anxiety Disorder Scale, 7-item (GAD-7)(weekly for three weeks)
- Peripartum Events Scale (PES)(weekly for three weeks)
- PROMIS Global Health(weekly for three weeks)
- Columbia-Suicide Severity Rating Scale (C-SSRS)(weekly for three weeks)
- plasma mirtazapine concentrations(weekly for three weeks)