Validating the Effect og Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum

Phase 2TerminatedNCT03785691

Nordsjaellands Hospital58 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hyperemesis Gravidarum Nausea Gravidarum Vomiting of Pregnancy

Interventions

MirtazapineDRUG

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.

OndansetronDRUG

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.

Eligibility

Sex: FEMALEMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 1. weight loss \>5% of pre-pregnancy weight and/or 2. hospitalisation due to nausea and vomiting of pregnancy * Singleton pregnancy * The subject must be willing and able to comply with trial protocol Exclusion Criteria: * 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

Locations (7)

Department of Gynaecology and Obstetrics, Aarhus University Hospital

Aarhus, Denmark

Department of Gynaecology and Obstetrics, Rigshospitalet

Copenhagen, Denmark

Department of Gynaecology and Obstetrics, Herlev Hospital

Herlev, Denmark

Department of Gynaecology and Obstetrics, Nordsjællands Hospital

Outcomes

Primary Outcomes

Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group.

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.

Time frame: 2 days

Change in nausea and vomiting from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.

Change in PUQE-24 score (patient reported) from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.

Time frame: 2 days

Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the mirtazapine group versus the placebo group.

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.

Time frame: 14 days

Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the ondansetron group versus the placebo group.

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.

Time frame: 14 days

Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group.

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.

Time frame: 2 days

Secondary Outcomes

Change in nausea and vomiting from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.

Data from ClinicalTrials.gov

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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.

Department of Gynaecology and Obstetrics, Hvidovre Hospital

Hvidovre, Denmark

Department of Gynaecology and Obstetrics, Kolding Sygehus

Kolding, Denmark

Department of Gynaecology and Obstetrics, Odense University Hospital

Odense, Denmark

Change in PUQE-24 score (patient reported) from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.

Overall nausea and vomiting during the intervention in the three different groups.

Area under the curve for PUQE-24 score (patient reported) during the intervention in the three different groups.

Time frame: 14 days

Change in well-being during the intervention in the three different groups.

Change in PUQE well-being score (patient reported) during the intervention in the three different groups.

Time frame: 14 days

Change in nausea during the intervention in the three different groups.

Change in daily nausea visual analog scale (VAS) (patient reported) during the intervention in the three different groups. VAS score ranges 0-100 with 0 being better and 100 being worse. Numbers are not visible to subjects.

Time frame: 14 days

Change in vomiting during the intervention in the three different groups.

Change in number of daily vomiting episodes (patient reported) during the intervention in the three different groups.

Time frame: 14 days

Occurrence of side effects in the three different groups.

Occurrence of side effects (patient reported and registered by trial personnel) during and until 5 days after the intervention in the three different groups.

Time frame: 19 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.

Change in Health-Related Quality of Life for Nausea and Vomiting during Pregnancy (NVPQOL) score (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups. NVPQOL score ranges 30-210 with 30 being better and 210 being worse.

Time frame: 14 days

Change in severity of hyperemesis gravidarum from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.

Change in HyperEmesis Level Prediction (HELP) score (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups. HELP score ranges 0-50 with 0 being better and 50 being worse.

Time frame: 14 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.

Change in health status (EQ-5D-5L) (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.

Time frame: 14 days

Change in sleep quality from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.

Change in modified Pittsburg Sleep Quality Index (PSQI) (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.Modified PSQI score ranges 0-12 with 0 being better and 12 being worse.

Time frame: 14 days

Patient satisfaction with treatment Day 7(+/-1) and Day 14(+/-1) in the three different groups.

Patient satisfaction with treatment VAS (patient reported) on Day 7(+/-1) and Day 14(+/-1) in the three different groups. VAS score ranges 0-100 with 0 being better and 100 being worse. Numbers are not visible to subjects.

Time frame: 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.

Change in patient consideration of termination of pregnancy (patient reported) from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.

Time frame: 14 days

Request for dosage increase in the three different groups.

Frequency of request for dosage increase in the three different groups.

Time frame: 14 days

Request for continuation of trial medication after end of intervention in the three different groups.

Frequency of request for continuation of trial medication after end of intervention in the three different groups.

Time frame: 14 days

Use of rescue medication during the intervention in the three different groups.

Use of rescue medication during (patient reported) the intervention in the three different groups.

Time frame: 14 days

Number of days on sick leave during the intervention in the three different groups

Number of days on sick leave (patient reported) during the intervention in the three different groups

Time frame: 14 days

Necessity of i.v.-fluids during the intervention in the three different groups.

Amount of treatments with i.v.-fluids during the intervention in the three different groups.

Time frame: 14 days

Need of hospitalisation during the intervention in the three different groups.

Number of days of hospitalisations during the intervention in the three different groups.

Time frame: 14 days

Weight change from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.

Weight change in kg from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.

Time frame: 14 days

Pregnancy outcome: Live birth, loss or termination of pregnancy

Live birth, loss or termination of pregnancy.

Time frame: 8 months

Delivery outcome: Mode of delivery

Mode of delivery: Vaginal, cesarian, vacuum extraction.

Time frame: 8 months

Delivery outcome: Delivery complications

Eg. postpartum hemorrhage, shoulder dystocia, sphincter rupture

Time frame: 8 months

Live birth outcome: birth weight.

Birth weight in g.

Time frame: 8 months

Live birth outcome: gestational age at birth.

Gestational age at birth in weeks plus days.

Time frame: 8 months

Live birth outcome: APGAR score.

APGAR score at 1, 5 and 10 minutes after birth. APGAR score ranges 0-10 with 0 being worse and 10 being better.

Time frame: 8 months

Live birth outcome: umbilical cord pH.

Umbilical cord pH at birth.

Time frame: 8 months

Live birth outcome: placenta weight.

placenta weight in g.

Time frame: 8 months

Live birth outcome: sex.

offsprings sex.

Time frame: 8 months

Live birth outcome: hospitalizations on neonatal ward during the first month post-partum.

Hospitalizations of the offspring in neonatal ward during the first month post-partum.

Time frame: 9 months

Live birth outcome: congenital malformations (depending on gestational age also registered on early ended pregnancies).

Congenital malformations.

Time frame: 8 months

Occurrence of treatment failure in the three different groups.

Frequency of and time to treatment failure in the three different groups.

Time frame: 14 days