Condition category
Pregnancy and Childbirth
Date applied
11/10/2015
Date assigned
19/11/2015
Last edited
30/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
It has been found that the more babies a pregnant mother is carrying, the more likely she is to give-birth early (preterm). Complications for the baby are usually very small, as most preterm births take place after 32 weeks. If the babies are born earlier than this, it can lead to heart, breathing or brain problems. Progesterone is a hormone which is naturally produced in a woman’s body. It plays an important part during pregnancy by helping to nurture the foetus and maintain the womb (uterus) through pregnancy. Studies have shown that progesterone can help to protect against preterm births in women carrying one baby (singleton pregnancy). So far this does not appear to be the case when a woman is carrying twins, however this may be because it is given too late during pregnancy at too low a dose. There are many types of progesterone available, and so the type used may also have an impact on its effectiveness at preventing preterm births. The aim of this study is to find out whether the progesterone containing product Utrogestan can help to prevent preterm births in women carrying twins.

Who can participate?
Women over 18 years of age who are pregnant with twins.

What does the study involve?
Participants are randomly allocated to one of two groups. The first group are asked to insert suppositories (a capsule which is placed in the vagina) containing 300mg progesterone twice a day until 34 weeks gestation (pregnancy) or earlier if the baby is born prematurely. The first group are asked to insert suppositories containing a placebo (dummy) twice a day until 34 weeks gestation (pregnancy) or earlier if the baby is born prematurely. At the end of the study, the amount of babies that are born prematurely are recorded, as well as any complications, such as low birth weight, need for special care or stillbirth.

What are the possible benefits and risks of participating?
Participants may benefit from the potential effect of progesterone in preventing preterm delivery. Not all participants will gain benefit because half of them will receive a placebo drug. Irrespective of which treatment group participants are assigned to, they will benefit from the close monitoring that they will receive. Participants will not be denied anything they would usually receive as part of routine care by being part of this study. Risks of participating are small, however some patients may experience some mild vaginal discharge or irritation. Previous studies involving progesterone in pregnancy have not reported any side effects. Progesterone is safe for pregnant women and their fetuses throughout pregnancy and is not associated with birth defects.

Where is the study run from?
Hospital Universitario “Virgen de la Arrixaca" (Spain) and six hospitals in the UK

When is the study starting and how long is it expected to run for?
March 2015 to March 2018

Who is funding the study?
Fetal Medicine Foundation (UK)

Who is the main contact?
1. Dr Catalina De Paco (Scientific)
2. Professor Kypros Nicolaides (Scientific)
3. Miss Liona Poon (Scientific)

Trial website

Contact information

Type

Scientific

Primary contact

Dr Catalina De Paco

ORCID ID

Contact details

Fetal Medicine Unit
Hospital Universitario “Virgen de la Arrixaca”
Murcia
30120
Spain

Type

Scientific

Additional contact

Prof Kypros Nicolaides

ORCID ID

Contact details

Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital
London
SE5 9RS
United Kingdom

Type

Scientific

Additional contact

Miss Liona Poon

ORCID ID

http://orcid.org/0000-0002-3944-4130

Contact details

Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital
London
SE5 9RS
United Kingdom

Additional identifiers

EudraCT number

2015-005180-16

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS: A randomised, placebo controlled, double-blinded trial- EVENTS

Acronym

EVENTS

Study hypothesis

In twin pregnancies, the use of a vaginal progesterone (urtogestan) started in the first trimester will reduce the chances of having a preterm birth before 34 weeks gestation.

Ethics approval

London Bridge REC, 22/02/2016, ref: 16/LO/0066

Study design

Multi-centre double-blind placebo-controlled randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Preterm birth

Intervention

All women with a twin pregnancy attending for their routine first trimester scan will be invited to participate in this randomised controlled trial of progesterone versus placebo. Informed and written consent will be sought from those agreeing to participate in the study. Participants are then randomly allocated to the treatment group or the placebo group.

Treatment group: Participants are required to insert a 300mg progesterone suppository twice daily until 34 weeks’ gestation or earlier in the event of preterm delivery.

Control Group: Participants are required to insert a 300mg placebo suppository twice daily until 34 weeks’ gestation or earlier in the event of preterm delivery.

Follow­-up clinical visits for all participants will be carried out at every 2-4 weeks. They will also be followed up by a further telephone interview 30 days after the last dose of medication.

Intervention type

Drug

Phase

Phase III

Drug names

Utrogestan

Primary outcome measures

Incidence of spontaneous delivery before 34 weeks (238 days) of gestation.

Secondary outcome measures

1. The incidence of spontaneous preterm birth <37 weeks (259 days) of gestation
2. Birth weight below the 3rd, 5th and 10th centile
3. Rate of stillbirth or neonatal death due to any cause
4. Major adverse outcomes before discharge from the hospital (intraventricular haemorrhage, respiratory distress syndrome, retinopathy of prematurity, or necrotising entercolitis)
5. Need for neonatal special care (admission to a neonatal intensive care unit, ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion)

Overall trial start date

01/03/2015

Overall trial end date

01/03/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 years or over
2. Dichorionic diamniotic (DCDA) or monochorionic diamniotic (MCDA) twin pregnancies;
3. Live fetuses at 11-13 weeks of gestation;
4. English or Spanish speaking (otherwise interpreters will be used)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1,180

Participant exclusion criteria

1. Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks assessment, including nuchal translucency thickness >3.5 mm
2. In MCDA twin pregnancies there are early signs of twin-to-twin transfusion syndrome (TTTS) (20% discordance in crown-rump length [CRL] and/or nuchal translucency [NT])
3. Women who are unconscious or severely ill, those with learning difficulties, or serious mental illness
4. Hypersensitivity to progesterone
5. Concurrent participation in another drug trial or at any time within the previous 28 days
6. Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol

Recruitment start date

01/04/2016

Recruitment end date

01/10/2017

Locations

Countries of recruitment

Spain, United Kingdom

Trial participating centre

Hospital Universitario “Virgen de la Arrixaca"
Murcia
30120
Spain

Trial participating centre

King's College Hospital London
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Medway Maritime Hospital
Windmill Road
Gillingham
ME7 5NY
United Kingdom

Trial participating centre

Southend University Hospital
Prittlewell Chase
Westcliff-on-Sea
SS0 0RY
United Kingdom

Trial participating centre

Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom

Trial participating centre

University Hospital Lewisham
High Street
London
SE13 6LH
United Kingdom

Trial participating centre

North Middlesex Hospital
Sterling Way
London
N18 1QX
United Kingdom

Sponsor information

Organisation

Foundation for Health Education & Research (Fundación para la Formación e Investigación Sanitaria)

Sponsor details

nº 1ª planta
Calle Luis Fontes Pagan
Murcia
30003
Spain

Sponsor type

Not defined

Website

Funders

Funder type

Charity

Funder name

Fetal Medicine Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Intention to publish the trial outcomes in peer reviewed journals. Results will also be made available at www.fetalmedicine.org/publications

Intention to publish date

01/09/2018

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

30/03/2016: Ethics approval information added.