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)
Study website
Contact information
Type
Scientific
Contact name
Dr Catalina De Paco
ORCID ID
Contact details
Fetal Medicine Unit
Hospital Universitario “Virgen de la Arrixaca”
Murcia
30120
Spain
Type
Scientific
Contact name
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
Contact name
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
Type
Scientific
Contact name
Mr Anoop Rehal
ORCID ID
Contact details
Fetal Medicine Research Institute
King’s College Hospital
16-20 Windsor Walk
London
SE5 8BB
United Kingdom
Additional identifiers
EudraCT/CTIS number
2015-005180-16
IRAS number
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(s)
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
Study setting(s)
Hospital
Study 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
Pharmaceutical study type(s)
Phase
Phase III
Drug/device/biological/vaccine name(s)
Utrogestan
Primary outcome measure
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 study start date
01/03/2015
Overall study end date
01/12/2019
Reason abandoned (if study stopped)
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(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Female
Target number of participants
1,180
Total final enrolment
1194
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
02/05/2017
Recruitment end date
18/04/2019
Locations
Countries of recruitment
England, Spain, United Kingdom
Study participating centre
Hospital Universitario “Virgen de la Arrixaca"
Murcia
30120
Spain
Study participating centre
King's College Hospital London
Denmark Hill
London
SE5 9RS
United Kingdom
Study participating centre
Medway Maritime Hospital
Windmill Road
Gillingham
ME7 5NY
United Kingdom
Study participating centre
Southend University Hospital
Prittlewell Chase
Westcliff-on-Sea
SS0 0RY
United Kingdom
Study participating centre
Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom
Study participating centre
University Hospital Lewisham
High Street
London
SE13 6LH
United Kingdom
Study 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
ROR
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
01/01/2020
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Data sharing statement to be made available at a later date
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Results article | results | 01/01/2021 | 26/01/2021 | Yes | No |
HRA research summary | 28/06/2023 | No | No |