ISRCTN ISRCTN14163439
DOI https://doi.org/10.1186/ISRCTN14163439
EudraCT/CTIS number 2014-002348-42
Secondary identifying numbers 18314
Submission date
11/02/2015
Registration date
11/02/2015
Last edited
02/07/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English Summary

Background and study aims
One in five pregnancies miscarry, and the loss of an unborn baby has the potential to cause both physical harm and psychological distress. A recently launched NICE guideline has urged that a large and robust randomised controlled clinical trial should be done to clarify whether progesterone treatment for women with bleeding in early pregnancy reduces the risk of miscarriage.

Who can participate?
Women between the ages of 18-39 who have experienced bleeding during the last 4 days in early pregnancy (up to 12 weeks).

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given progesterone capsules to place into their vagina twice a day to up to 16 weeks of pregnancy. Those in group 2 are given placebo capsules to be administered in the same way. The main outcome of the study is live birth beyond 34 weeks of pregnancy. A number of other key outcome measures, including gestation at birth, miscarriage rates and the condition of the baby at 28 days of life, are also collected and analysed and we gather resource-use outcomes to perform a health economic evaluation.

What are the possible benefits and risks of participating?
We do not know whether each participant will benefit personally from taking part in this study, but the knowledge gained thanks to their help will inform future treatment and potentially lead to improved antenatal care and pregnancy outcomes for women in the future. Previous studies using progesterone treatment during pregnancy have found very little evidence of risks for the mother or the baby. However, some women may experience swollen hands or feet, bloating, headache, sleeplessness, diarrhoea or jaundice.

Where is the study run from?
48 NHS hospitals in the UK

When is the study starting and how long is it expected to run for?
October 2014 to June 2018

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Professor Arri Coomarasamy

Contact information

Dr Adam Devall
Scientific

Birmingham Clinical Trials Unit (BCTU)
Institute of Applied Health Research
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Study information

Study designRandomised; Interventional; Design type: Not specified, Prevention
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Community
Study typeTreatment
Participant information sheet Not available in web format, please use contact details to request a patient information sheet
Scientific titleEffectiveness of progesterone to prevent miscarriage in women with early pregnancy bleeding: A randomised placebo-controlled trial (PRISM Trial: PRogesterone In Spontaneous Miscarriage Trial)
Study acronymPRISM
Study hypothesisThe aim of this trial is to clarify the evidence that progesterone treatment for women with bleeding in early pregnancy can reduce the risk of miscarriage.
Ethics approval(s)NRES Committee South Central – Oxford C, 26/11/2014, ref: 14-SC-1345
ConditionTopic: Reproductive health and childbirth; Subtopic: Reproductive Health and Childb (all Subtopics); Disease: Reproductive Health & Childbirth
Intervention1. Placebo: The placebo will be a vaginal capsule, encapsulated in the same form as the IMP, and identical in colour, shape and weight
2. Progesterone: The Investigational Medicinal Product (IMP) is progesterone at a dose of 400mg to be taken as vaginal pessaries twice daily from confirmation of an intrauterine gestation sac visible on ultrasonography until 16 completed weeks of pregnancy or until miscarriage is confirmed
Intervention typeDrug
Pharmaceutical study type(s)
Phase
Drug / device / biological / vaccine name(s)Progesterone
Primary outcome measureLive birth beyond 34 completed weeks of gestation is assessed using medical record review at pregnancy end.
Secondary outcome measuresSecondary outcome measures as of 01/02/2017:
1. Time from conception to pregnancy end (any reason) is assessed using medical record review at pregnancy end. Conception date will be estimated using the patient’s booking scan if available or, if not, the date of last menstrual period or, failing that, the date from the ultrasound scan.
2. Ongoing pregnancy at 12 weeks (range 11 to 14 weeks) of gestation is assessed using medical record review at 11-14 weeks gestation
3. Miscarriage rate (defined as delivery before 24 weeks of gestation) is assessed using medical record review at pregnancy end
4. Other pregnancy end outcomes: live birth <34 weeks, ectopic pregnancy, termination, stillbirth, molar pregnancy, resolved pregnancy of unknown location (PUL), failed PUL, twin live births, gestational age at miscarriage is assessed using medical record review at pregnancy end
5. Where live birth ≥24 weeks: time from conception to delivery (gestational age), gestational age <28/<32/<37 weeks, mode of delivery (unassisted vaginal, instrumental vaginal, elective c-section, emergency c-section, vaginal breech delivery, other), birth weight, arterial and venous cord pH, APGAR scores, base excess is assessed using medical record review at pregnancy end
6. Antenatal complications: pregnancy-induced hypertension, pre-eclampsia, obstetric cholestasis, cervical cerclarge, preterm (<37 weeks) pre-labour rupture of membranes, gestational diabetes (other complications will be tabulated but not formally analysed) (medical record review)
7. Intrapartum complications: chorioamnionitis, intrauterine growth restriction (IUGR), macrosomia (other complications will be tabulated but not formally analysed) is assessed using medical record review at pregnancy end
8. Post-partum complications: haemorrhage (other complications will be tabulated but not formally analysed) is assessed using medical record review at pregnancy end
9. Maternal complications: admission to high dependency unit (HDU), admission to intensive therapy unit (ITU), (other complications will be tabulated but not formally analysed) is assessed using medical record review up to 28 days after pregnancy end
10. Neonatal complications: discharge to hospital, early infection, retinopathy of prematurity, necrotising enterocolitis, intraventricular haemorrhage, congenital and chromosomal abnormalities, respiratory distress syndrome, ventilation or oxygen support (other complications will be tabulated but not formally analysed is assessed using medical record review up to 28 days after live birth
11. Survival at 28 days of neonatal life is assessed using medical record review up to 28 days after live birth
12. Maternal adverse events (tabulated but not formally analysed) is assessed using medical record review throughout pregnancy and up to 28 days of neonatal life
13. Serious adverse events are assessed using medical record review throughout pregnancy and up to 28 days of neonatal life

Original secondary outcome measures:
1. Adverse events; Timepoint(s): Throughout pregnancy and up to 28 days of neonatal life
2. Antenatal complications; Timepoint(s): Until pregnancy end
3. APGAR score; Timepoint(s): Pregnancy end beyond 24 weeks
4. Arterial cord pH; Timepoint(s): Pregnancy end beyond 24 weeks
5. Birthweight; Timepoint(s): Pregnancy end beyond 24 weeks
6. Chromosomal and congenital abnormalities; Timepoint(s): Pregnancy end
7. Gestation at delivery; Timepoint(s): Pregnancy end
8. Miscarriage; Timepoint(s): Up to 24 weeks of gestation
9. Mode of delivery; Timepoint(s): Pregnancy end beyond 24 weeks
10. Neonatal complications; Timepoint(s): Live birth
11. Neonatal survival; Timepoint(s): 28 days of neonatal life
12. Ongoing pregnancy at 12 weeks of gestation; Timepoint(s): 11-13 weeks of gestation
13. Requirements for resuscitation; Timepoint(s): Pregnancy end beyond 24 weeks
14. Resource use; Timepoint(s): Throughout pregnancy and up to 28 days of neonatal life
15. Surfactant use; Timepoint(s): Live birth
16. Venous cord pH; Timepoint(s): Pregnancy end beyond 24 weeks
17. Ventilation support; Timepoint(s): Live birth
Overall study start date01/10/2014
Overall study end date30/06/2018

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target number of participantsPlanned Sample Size: 4150; UK Sample Size: 4150
Total final enrolment4153
Participant inclusion criteriaCorrect as of 01/02/2017
1. Women presenting with with early pregnancy vaginal bleeding that has occurred within the last 4 days and is in the first 12 weeks of pregnancy
2. Upper Age Limit 39 years
3. Lower Age Limit 18 years

Previous inclusion criterion:
1. Women presenting with vaginal bleeding in the first 12 weeks of pregnancy with an intrauterine gestation sac visible on ultrasonography
Participant exclusion criteria1. Women of age less than 18 years or more than 40
2. Women with life-threatening bleeding
3. Women already taking progesterone supplementation therapy
4. Women with contraindications to progesterone use
Recruitment start date01/03/2015
Recruitment end date28/07/2017

Locations

Countries of recruitment

  • England
  • Scotland
  • United Kingdom

Study participating centres

Birmingham Women's Hospital
Metchley Park Road
Edgbaston
Birmingham
B15 2TG
United Kingdom
Queen Charlotte's and Chelsea Hospital
London
W12 0HS
United Kingdom
Royal Infirmary of Edinburgh
Edinburgh
EH16 4SA
United Kingdom
Liverpool Women's Hospital
Liverpool
L8 7SS
United Kingdom
Birmingham Heartlands Hospital
Birmingham
B9 5SS
United Kingdom
University College London Hospital
London
NW1 2BU
United Kingdom
Chelsea and Westminster Hospital
London
SW15 2QJ
United Kingdom
St Michael’s University Hospital
Bristol
BS2 8UG
United Kingdom
Queen's Medical Centre
Nottingham
NG7 2UH
United Kingdom
Sunderland Royal Hospital
Sunderland
SR4 7TP
United Kingdom
Princess Royal Hospital
Glasgow
G31 2ER
United Kingdom
University Hospital Coventry
Coventry
CV2 2DX
United Kingdom

Sponsor information

University of Birmingham
University/education

Edgbaston
Birmingham
B15 2TT
England
United Kingdom

ROR logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location
United Kingdom

Results and Publications

Intention to publish date30/06/2019
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planA meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication in an open access journal.
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 09/05/2019 09/05/2019 Yes No
Other publications cost-effectiveness analysis 01/05/2020 Yes No
Results article results 01/06/2020 02/07/2020 Yes No

Editorial Notes

02/07/2020: Publication reference added.
03/02/2020: Publication reference added.
09/05/2019: Publication reference and total final enrolment number added.
24/07/2017: Recruitment end date has been updated from 21/07/2017 to 28/07/2017.
14/07/2017: Recruitment end date has been updated from 14/07/2017 to 21/07/2017.
29/06/2017: Recruitment end date has been updated from 31/05/2017 to 14/07/2017.
01/02/2017: The following changes have been made to the record:
1. The study contact has been changed from Arri Coomarasamy to Adam Devall
2. The secondary outcome measures have been updated
3. The first inclusion criterion has been updated
4. The plain English summary has been updated to reflect the above changes in the record
11/10/2016: Overall study end date changed from 30/09/2017 to 30/06/2018. Recruitment end date changed from 01/04/2016 to 31/05/2017