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Hyperemesis GravidarumPhase 2VOMITNCT03785691

Validating the Effect og Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum

A Phase 2 study testing Mirtazapine and Ondansetron in people with Hyperemesis Gravidarum and Nausea Gravidarum, run by Nordsjaellands Hospital at 7 sites in Denmark.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
What is being tested?
Mirtazapine and Ondansetron
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
7 sitesDenmark
Study dates
1 Mar 2019to 31 Jul 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • hospitalisation due to nausea and vomiting of pregnancy
  • Singleton pregnancy
  • The subject must be willing and able to comply with trial protocol

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Denmark7 sites
  • Department of Gynaecology and Obstetrics, Aarhus University Hospital

    Aarhus, 8200

  • Department of Gynaecology and Obstetrics, Rigshospitalet

    Copenhagen, 2100

  • Department of Gynaecology and Obstetrics, Herlev Hospital

    Herlev, 2730

  • Department of Gynaecology and Obstetrics, Nordsjællands Hospital

    Hillerød, 3400

  • Department of Gynaecology and Obstetrics, Hvidovre Hospital

    Hvidovre, 2650

  • Department of Gynaecology and Obstetrics, Kolding Sygehus

    Kolding, 6000

  • Department of Gynaecology and Obstetrics, Odense University Hospital

    Odense, 5000

Other trials in Denmark

About this study

Official title: Validating the Effect of Ondansetron and Mirtazapine in Treating Hyperemesis Gravidarum: A Double-Blind Randomised Placebo-Controlled Multicentre Trial

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).

Being tested
Mirtazapine, Ondansetron, Placebo
Keywords
Hyperemesis Gravidarum (HG), Mirtazapine, Ondansetron, Pregnancy, Nausea and Vomiting of Pregnancy (NVP), Randomized Controlled Trial (RCT)
Medical subject headings
Hyperemesis Gravidarum, Nausea

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MirtazapineDrug

    Also called KRKA Mirtazapine Oral Tablet

    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

    Also called Bluefish Ondansetron Oral Tablet

    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.

  • PlaceboDrug

    Also called Placebo Oral Tablet

    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.

Study groups in NCT03785691
Study groupRoleWhat they receive
MirtazapineExperimentalMirtazapine 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.
Receives: Drug: Mirtazapine
OndansetronExperimentalOndansetron 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.
Receives: Drug: Ondansetron
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 days

  2. 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.

    Measured: 2 days

  3. 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.

    Measured: 14 days

  4. 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.

    Measured: 14 days

  5. 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.

    Measured: 2 days

Secondary outcomes (31)
  1. Change in nausea and vomiting from baseline to Day 14(+/-1) in the mirtazapine group versus the ondansetron group.

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

    Measured: 14 days

  2. 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.

    Measured: 14 days

  3. 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.

    Measured: 14 days

  4. 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.

    Measured: 14 days

  5. 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.

    Measured: 14 days

  6. 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.

    Measured: 19 days

  7. 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.

    Measured: 14 days

  8. 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.

    Measured: 14 days

  9. 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.

    Measured: 14 days

  10. 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.

    Measured: 14 days

  11. 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.

    Measured: 14 days

  12. 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.

    Measured: 14 days

  13. Request for dosage increase in the three different groups.

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

    Measured: 14 days

  14. 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.

    Measured: 14 days

  15. 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.

    Measured: 14 days

  16. 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

    Measured: 14 days

  17. 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.

    Measured: 14 days

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

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

    Measured: 14 days

  19. 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.

    Measured: 14 days

  20. Pregnancy outcome: Live birth, loss or termination of pregnancy

    Live birth, loss or termination of pregnancy.

    Measured: 8 months

  21. Delivery outcome: Mode of delivery

    Mode of delivery: Vaginal, cesarian, vacuum extraction.

    Measured: 8 months

  22. Delivery outcome: Delivery complications

    Eg. postpartum hemorrhage, shoulder dystocia, sphincter rupture

    Measured: 8 months

  23. Live birth outcome: birth weight.

    Birth weight in g.

    Measured: 8 months

  24. Live birth outcome: gestational age at birth.

    Gestational age at birth in weeks plus days.

    Measured: 8 months

  25. 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.

    Measured: 8 months

  26. Live birth outcome: umbilical cord pH.

    Umbilical cord pH at birth.

    Measured: 8 months

  27. Live birth outcome: placenta weight.

    placenta weight in g.

    Measured: 8 months

  28. Live birth outcome: sex.

    offsprings sex.

    Measured: 8 months

  29. 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.

    Measured: 9 months

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

    Congenital malformations.

    Measured: 8 months

  31. Occurrence of treatment failure in the three different groups.

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

    Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2018
  2. Study start1 Mar 2019
  3. Primary completion31 Jul 2022
  4. Study completion31 Jul 2022

Why it stopped: Recruiting difficulties

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized placebo controlled multicenter trial testing already marketed drugs on a new indication.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03785691
Sponsor's protocol ID
VOMIT
Acronym
VOMIT
Status last verified
Jan 2023
First submitted
13 Nov 2018
Last updated
30 Jan 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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. 2026 Jun;234(6):1700-1729. doi: 10.1016/j.ajog.2025.12.061. Epub 2025 Dec 30.

    PubMed 41478546
  • 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.

    PubMed 32209630

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mirtazapine and Ondansetron in people with Hyperemesis Gravidarum and Nausea Gravidarum, run by Nordsjaellands Hospital at 7 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Recruiting difficulties). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in nausea and vomiting from baseline to Day 2 (short term) in the mirtazapine group versus the placebo group. (time frame: 2 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03785691, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.

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