Prevention of preterm birth in twin pregnancies - “Randomised trial of progesterone versus placebo”
| ISRCTN | ISRCTN66445401 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN66445401 |
| Clinical Trials Information System (CTIS) | 2015-005180-16 |
| Protocol serial number | N/A |
| Sponsor | Foundation for Health Education & Research (Fundación para la Formación e Investigación Sanitaria) |
| Funder | Fetal Medicine Foundation |
- Submission date
- 11/10/2015
- Registration date
- 19/11/2015
- Last edited
- 26/01/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
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)
Contact information
Scientific
Fetal Medicine Unit
Hospital Universitario “Virgen de la Arrixaca”
Murcia
30120
Spain
Scientific
Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital
London
SE5 9RS
United Kingdom
Scientific
Harris Birthright Research Centre for Fetal Medicine
King’s College Hospital
London
SE5 9RS
United Kingdom
 ORCID ID |
0000-0002-3944-4130 |
|---|
Scientific
Fetal Medicine Research Institute
King’s College Hospital
16-20 Windsor Walk
London
SE5 8BB
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multi-centre double-blind placebo-controlled randomised trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS: A randomised, placebo controlled, double-blinded trial- EVENTS |
| Study acronym | EVENTS |
| Study objectives | 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 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Utrogestan |
| Primary outcome measure(s) | Incidence of spontaneous delivery before 34 weeks (238 days) of gestation. |
| Key secondary outcome measure(s) | 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) |
| Completion date | 01/12/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target sample size at registration | 1180 |
| Total final enrolment | 1194 |
| Key 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) |
| Key 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 |
| Date of first enrolment | 02/05/2017 |
| Date of final enrolment | 18/04/2019 |
Locations
Countries of recruitment
- United Kingdom
- England
- Spain
Study participating centres
30120
Spain
London
SE5 9RS
United Kingdom
Gillingham
ME7 5NY
United Kingdom
Westcliff-on-Sea
SS0 0RY
United Kingdom
London
E9 6SR
United Kingdom
London
SE13 6LH
United Kingdom
London
N18 1QX
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan |
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 | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
26/01/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
15/01/2020: Internal review.
14/01/2020: The scientific contact has been changed.
13/01/2020: The following changes have been made:
1. The recruitment start date has been changed from 01/04/2016 to 02/05/2017.
2. The recruitment end date has been changed from 01/10/2017 to 18/04/2019.
3. The overall end date has been changed from 01/03/2018 to 01/12/2019.
4. The intention to publish date has been changed from 01/09/2018 to 01/01/2020.
12/05/2017: Internal review
30/03/2016: Ethics approval information added.
