Validating the Effect of Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum: A Double-Blind Randomised Placebo-Controlled Multicentre Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 58
- 试验地点
- 7
- 主要终点
- Change in nausea and vomiting from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.
研究概览
简要总结
The aim is to investigate the efficacy of mirtazapine and ondansetron as treatment for hyperemesis gravidarum(HG).
The setup is a double-blind multicenter trial where patients suffering from HG will be randomized to treatment with either mirtazapine, ondansetron or placebo (1:1:1).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All oral tablets will be encapsulated in gelatine to ensure identical look, smell and taste.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Written informed consent obtained before any trial related procedures are performed
- •Female age >18 years
- •Pregnant woman with gestational age between 5+0 and 19+6
- •Nausea and vomiting without other obvious reason
- •PUQE-24 score ≥13 OR PUQE-24 score ≥7 AND
- •weight loss >5% of pre-pregnancy weight and/or
- •hospitalisation due to nausea and vomiting of pregnancy
- •Singleton pregnancy
- •The subject must be willing and able to comply with trial protocol
排除标准
- •Mola pregnancy, multiple gestation or non-vital pregnancy
- •Nausea and vomiting of other aetiology than NVP
- •Allergic to selective 5-HT3-receptor antagonists
- •Ongoing treatment with antidepressant medication
- •Pre-existing diagnosis of chronic kidney disease, diabetes type 1 or 2, significant cardiac disease (incl. long QT syndrome), epilepsy, HIV. In case of other pre-existing conditions subjects might be excluded based on individual assessment by an MD
- •Elevated liver enzymes (ALAT>150 U/l)
- •Elevated creatinine (>100 µmol/l)
- •ECG showing long QT-syndrome (QTc >460msek)
- •Weekly alcohol intake >2 units of alcohol
- •Not able to take medicine orally
- •Not able to understand spoken and/or written Danish
- •Participation in another investigational drug trial within current pregnancy
研究组 & 干预措施
Mirtazapine
Mirtazapine 15 mg oral tablet (incapsulated in gelatine to provide blinding) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered once daily (morning).
On Day 7 dosage increase is optional. If desired, mirtazapine 30 mg oral tablet (incapsulated in gelatine) will be administered once daily (bedtime) for 7 days. Placebo (empty gelatine capsule) will be administered three times daily (morning, noon and late afternoon). In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
干预措施: Mirtazapine (Drug)
Ondansetron
Ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered twice daily (morning and bedtime) for 7 days.
On Day 7 dosage increase is optional. If desired, ondansetron 8 mg oral tablet (incapsulated in gelatine) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
干预措施: Ondansetron (Drug)
Placebo
Placebo oral tablet (empty gelatine capsule) will be administered twice daily (morning and bedtime) for 7 days.
On Day 7 dosage increase is optional. If desired, placebo oral tablet (empty gelatine capsule) will be administered four times daily (morning, noon, late afternoon and bedtime) for 7 days. In case dosage increase is not desired, the subject will continue the initial treatment for an additional 7 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in nausea and vomiting from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.
时间窗: 2 days
Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.
Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group.
时间窗: 2 days
Change in Pregnancy Unique Quantification of Emesis 24 score (PUQE-24 score) (patient reported) from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group. PUQE-24 score ranges 3-15 with 3 being better and 15 being worse.
Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the mirtazapine group versus the placebo group.
时间窗: 14 days
Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-) (long term) in the mirtazapine group versus the placebo group. Only tested if outcome 1 is significant.
Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the ondansetron group versus the placebo group.
时间窗: 14 days
Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-) (long term) in the ondansetron group versus the placebo group. Only tested if outcome 2 is significant.
Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group.
时间窗: 2 days
Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group. Only tested if outcome 1 is significant.
次要结局
- Change in severity of hyperemesis gravidarum from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.(14 days)
- Change in sleep quality from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.(14 days)
- Change in nausea and vomiting from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.(14 days)
- Change in vomiting during the intervention in the three different groups.(14 days)
- Occurrence of side effects in the three different groups.(19 days)
- Change in health-related quality of life from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.(14 days)
- Request for dosage increase in the three different groups.(14 days)
- Request for continuation of trial medication after end of intervention in the three different groups.(14 days)
- Use of rescue medication during the intervention in the three different groups.(14 days)
- Number of days on sick leave during the intervention in the three different groups(14 days)
- Overall nausea and vomiting during the intervention in the three different groups.(14 days)
- Change in well-being during the intervention in the three different groups.(14 days)
- Change in quality of life for nausea and vomiting during pregnancy from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.(14 days)
- Patient satisfaction with treatment Day 7(+/-1) and Day 14(+/-1) in the three different groups.(14 days)
- Change in patient consideration of termination of pregnancy from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.(14 days)
- Change in nausea during the intervention in the three different groups.(14 days)
- Necessity of i.v.-fluids during the intervention in the three different groups.(14 days)
- Need of hospitalisation during the intervention in the three different groups.(14 days)
- Weight change from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.(14 days)
- Pregnancy outcome: Live birth, loss or termination of pregnancy(8 months)
- Delivery outcome: Mode of delivery(8 months)
- Delivery outcome: Delivery complications(8 months)
- Live birth outcome: birth weight.(8 months)
- Live birth outcome: gestational age at birth.(8 months)
- Live birth outcome: APGAR score.(8 months)
- Live birth outcome: umbilical cord pH.(8 months)
- Live birth outcome: sex.(8 months)
- Live birth outcome: congenital malformations (depending on gestational age also registered on early ended pregnancies).(8 months)
- Live birth outcome: placenta weight.(8 months)
- Live birth outcome: hospitalizations on neonatal ward during the first month post-partum.(9 months)
- Occurrence of treatment failure in the three different groups.(14 days)
研究者
Anne Ostenfeld
MD, PhD student
Nordsjaellands Hospital