PRISM: Progesterone in spontaneous miscarriage
| 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
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
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 design | Randomised; Interventional; Design type: Not specified, Prevention |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a patient 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 hypothesis | 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 |
| Condition | 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 |
| Pharmaceutical study type(s) | |
| Phase | |
| Drug / device / biological / vaccine name(s) | Progesterone |
| Primary outcome measure | Live birth beyond 34 completed weeks of gestation is assessed using medical record review at pregnancy end. |
| Secondary outcome measures | 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 |
| Overall study start date | 01/10/2014 |
| Overall study end date | 30/06/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 4150; UK Sample Size: 4150 |
| Total final enrolment | 4153 |
| Participant 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 |
| Participant 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 |
| Recruitment start date | 01/03/2015 |
| Recruitment end date | 28/07/2017 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Edgbaston
Birmingham
B15 2TG
United Kingdom
W12 0HS
United Kingdom
EH16 4SA
United Kingdom
L8 7SS
United Kingdom
B9 5SS
United Kingdom
NW1 2BU
United Kingdom
SW15 2QJ
United Kingdom
BS2 8UG
United Kingdom
NG7 2UH
United Kingdom
SR4 7TP
United Kingdom
G31 2ER
United Kingdom
CV2 2DX
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
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 date | 30/06/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | A 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
