NCT03785691

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).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
58

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2019

Typical duration for phase_2

Geographic Reach
1 country

7 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 13, 2018

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 24, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2019

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2022

Completed
Last Updated

January 30, 2023

Status Verified

January 1, 2023

Enrollment Period

3.4 years

First QC Date

November 13, 2018

Last Update Submit

January 26, 2023

Conditions

Hyperemesis GravidarumNausea GravidarumVomiting of Pregnancy

Keywords

Hyperemesis Gravidarum (HG)MirtazapineOndansetronPregnancyNausea and Vomiting of Pregnancy (NVP)Randomized Controlled Trial (RCT)

Outcome Measures

Primary Outcomes (5)

  • 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.

    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.

    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.

    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.

    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.

    2 days

Secondary Outcomes (31)

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

    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 nausea during the intervention in the three different groups.

    14 days

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

    14 days

  • +26 more secondary outcomes

Study Arms (3)

Mirtazapine

EXPERIMENTAL

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.

Drug: Mirtazapine

Ondansetron

EXPERIMENTAL

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.

Drug: Ondansetron

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

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.

Also known as: KRKA Mirtazapine Oral Tablet
Mirtazapine
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.

Also known as: Bluefish Ondansetron Oral Tablet
Ondansetron
PlaceboDRUG

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.

Also known as: Placebo Oral Tablet
Placebo

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Department of Gynaecology and Obstetrics, Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Department of Gynaecology and Obstetrics, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Department of Gynaecology and Obstetrics, Herlev Hospital

Herlev, 2730, Denmark

Location

Department of Gynaecology and Obstetrics, Nordsjællands Hospital

Hillerød, 3400, Denmark

Location

Department of Gynaecology and Obstetrics, Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Department of Gynaecology and Obstetrics, Kolding Sygehus

Kolding, 6000, Denmark

Location

Department of Gynaecology and Obstetrics, Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (2)

  • Ostenfeld A, Carlsen SE, Jensen AK, Futtrup TB, Westergaard HB, Pedersen LH, Andersen JT, Petersen TS, Lokkegaard ECL; VOMIT investigation group. Mirtazapine or ondansetron for hyperemesis gravidarum: a randomized placebo-controlled trial. Am J Obstet Gynecol. 2025 Dec 30:S0002-9378(25)00982-2. doi: 10.1016/j.ajog.2025.12.061. Online ahead of print.

    PMID: 41478546DERIVED

  • 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.

    PMID: 32209630DERIVED

MeSH Terms

Conditions

Hyperemesis GravidarumNausea

Interventions

MirtazapineOndansetron

Condition Hierarchy (Ancestors)

Morning SicknessPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesVomitingSigns and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DibenzazepinesHeterocyclic Compounds, 3-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsImidazolesAzolesHeterocyclic Compounds, 1-RingCarbazolesIndolesHeterocyclic Compounds, 2-Ring

Study Officials

  • Anne Ostenfeld, MD

    Department of Obstetrics and gynecology, Nordsjællands Hospital Hillerød

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
All oral tablets will be encapsulated in gelatine to ensure identical look, smell and taste.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized placebo controlled multicenter trial testing already marketed drugs on a new indication.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD student

Study Record Dates

First Submitted

November 13, 2018

First Posted

December 24, 2018

Study Start

March 1, 2019

Primary Completion

July 31, 2022

Study Completion

July 31, 2022

Last Updated

January 30, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will share

Access to patient level data and supporting clinical documents may be requested. Requests will be reviewed on the basis of methodological proposal. Patient data will be de-identified to protect the privacy of trial patients in line with applicable laws and regulations.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Following publication, no end date.

Locations

DK(7)