PRISM: Progesterone in spontaneous miscarriage

ISRCTN	ISRCTN14163439
DOI	https://doi.org/10.1186/ISRCTN14163439
Clinical Trials Information System (CTIS)	2014-002348-42
Protocol serial number	18314
Sponsor	University of Birmingham
Funder	National Institute for Health Research

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 of protocol

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

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Not specified, Prevention
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effectiveness of progesterone to prevent miscarriage in women with early pregnancy bleeding: A randomised placebo-controlled trial (PRISM Trial: PRogesterone In Spontaneous Miscarriage Trial)
Study acronym	PRISM
Study objectives	The 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
Health condition(s) or problem(s) studied	Topic: Reproductive health and childbirth; Subtopic: Reproductive Health and Childb (all Subtopics); Disease: Reproductive Health & Childbirth
Intervention	1. 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 type	Drug
Phase
Drug / device / biological / vaccine name(s)	Progesterone
Primary outcome measure(s)	Live birth beyond 34 completed weeks of gestation is assessed using medical record review at pregnancy end.
Key secondary outcome measure(s)	Secondary 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
Completion date	30/06/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	4150
Total final enrolment	4153
Key inclusion criteria	Correct 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
Key exclusion criteria	1. 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
Date of first enrolment	01/03/2015
Date of final enrolment	28/07/2017

Locations

Countries of recruitment

United Kingdom
England
Scotland

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

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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
Results article	results	01/06/2020	02/07/2020	Yes	No
Other publications	cost-effectiveness analysis	01/05/2020		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

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