Clinical trial NCT03785691: Validating the Effect og Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum
Official title: Validating the Effect of Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum: A Double-Blind Randomised Placebo-Controlled Multicentre Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hyperemesis Gravidarum
Nausea Gravidarum
Vomiting of Pregnancy
Keywords: Hyperemesis Gravidarum (HG)
Mirtazapine
Ondansetron
Pregnancy
Nausea and Vomiting of Pregnancy (NVP)
Randomized Controlled Trial (RCT)
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
name: Aarhus University Hospital
name: Herlev and Gentofte Hospital
name: Hvidovre University Hospital
name: Odense University Hospital
name: Rigshospitalet, Denmark
name: Regionernes Medicinpulje
name: Kolding Sygehus
First posted: 2018-12-24
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo controlled multicenter trial testing already marketed drugs on a new indication.
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group.
timeFrame: 2 days
measure: Change in nausea and vomiting from baseline to Day 2 (short term) in the ondansetron group versus the placebo group.
timeFrame: 2 days
measure: Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the mirtazapine group versus the placebo group.
timeFrame: 14 days
measure: Change in nausea and vomiting from baseline to Day 14(+/-1) (long term) in the ondansetron group versus the placebo group.
timeFrame: 14 days
measure: Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the ondansetron group.
timeFrame: 2 days
Secondary outcomes:
measure: Change in nausea and vomiting from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.
timeFrame: 14 days
measure: Overall nausea and vomiting during the intervention in the three different groups.
timeFrame: 14 days
measure: Change in well-being during the intervention in the three different groups.
timeFrame: 14 days
measure: Change in nausea during the intervention in the three different groups.
timeFrame: 14 days
measure: Change in vomiting during the intervention in the three different groups.
timeFrame: 14 days
measure: Occurrence of side effects in the three different groups.
timeFrame: 19 days
measure: 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.
timeFrame: 14 days
measure: Change in severity of hyperemesis gravidarum from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
timeFrame: 14 days
measure: Change in health-related quality of life from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
timeFrame: 14 days
measure: Change in sleep quality from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
timeFrame: 14 days
measure: Patient satisfaction with treatment Day 7(+/-1) and Day 14(+/-1) in the three different groups.
timeFrame: 14 days
measure: 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.
timeFrame: 14 days
measure: Request for dosage increase in the three different groups.
timeFrame: 14 days
measure: Request for continuation of trial medication after end of intervention in the three different groups.
timeFrame: 14 days
measure: Use of rescue medication during the intervention in the three different groups.
timeFrame: 14 days
measure: Number of days on sick leave during the intervention in the three different groups
timeFrame: 14 days
measure: Necessity of i.v.-fluids during the intervention in the three different groups.
timeFrame: 14 days
measure: Need of hospitalisation during the intervention in the three different groups.
timeFrame: 14 days
measure: Weight change from baseline to Day 7(+/-1) and baseline to Day 14(+/-1) in the three different groups.
timeFrame: 14 days
measure: Pregnancy outcome: Live birth, loss or termination of pregnancy
timeFrame: 8 months
measure: Delivery outcome: Mode of delivery
timeFrame: 8 months
measure: Delivery outcome: Delivery complications
timeFrame: 8 months
measure: Live birth outcome: birth weight.
timeFrame: 8 months
measure: Live birth outcome: gestational age at birth.
timeFrame: 8 months
measure: Live birth outcome: APGAR score.
timeFrame: 8 months
measure: Live birth outcome: umbilical cord pH.
timeFrame: 8 months
measure: Live birth outcome: placenta weight.
timeFrame: 8 months
measure: Live birth outcome: sex.
timeFrame: 8 months
measure: Live birth outcome: hospitalizations on neonatal ward during the first month post-partum.
timeFrame: 9 months
measure: Live birth outcome: congenital malformations (depending on gestational age also registered on early ended pregnancies).
timeFrame: 8 months
measure: Occurrence of treatment failure in the three different groups.
timeFrame: 14 days
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Gynaecology and Obstetrics, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Gynaecology and Obstetrics, Rigshospitalet
city: Herlev
country: Denmark
facility: Department of Gynaecology and Obstetrics, Herlev Hospital
city: Hillerød
country: Denmark
facility: Department of Gynaecology and Obstetrics, Nordsjællands Hospital
city: Hvidovre
country: Denmark
facility: Department of Gynaecology and Obstetrics, Hvidovre Hospital
city: Kolding
country: Denmark
facility: Department of Gynaecology and Obstetrics, Kolding Sygehus
city: Odense
country: Denmark
facility: Department of Gynaecology and Obstetrics, Odense University Hospital
Study officials:
affiliation: Department of Obstetrics and gynecology, Nordsjællands Hospital Hillerød
name: Anne Ostenfeld, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ostenfeld A, Petersen TS, Futtrup TB, Andersen JT, Jensen AK, Westergaard HB, Pedersen LH, Lokkegaard ECL. Validating the effect of Ondansetron and Mirtazapine In Treating hyperemesis gravidarum (VOMIT): protocol for a randomised placebo-controlled trial. BMJ Open. 2020 Mar 24;10(3):e034712. doi: 10.1136/bmjopen-2019-034712.