Condition category
Pregnancy and Childbirth
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
This study was undertaken to test whether giving the hormone progesterone to pregnant women with a history of repeated unexplained early pregnancy losses could increase the number of pregnancies leading to live births after at least 24 weeks of gestation.

Who can participate?
Women aged 18-39 with unexplained recurrent miscarriages (three or more consecutive or non-consecutive first trimester miscarriages). A pregnancy loss is considered to be unexplained if conditions known to increase the risk of miscarriage are absent.

What does the study involve?
Participants were randomly allocated to one of two groups: one group received progesterone twice daily as vaginal pessaries and the other group received a placebo (dummy) with an identical appearance, from soon after a positive urinary pregnancy test, and no later than 6 weeks of pregnancy, until 12 completed weeks of pregnancy (or earlier if the pregnancy ended before 12 weeks).

What are the possible benefits and risks of participating?
There is substantial evidence from IVF practice that progesterone supplementation is safe to the mother and fetus at the proposed dose. Moreover, recent studies of vaginal progesterone in the context of prevention of preterm birth have not shown any evidence of short-term safety concerns in the participants.

Where is the study run from?
45 hospitals in the UK and the Netherlands

When is the study starting and how long is it expected to run for?
From May 2009 to September 2014

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
1. Dr Arri Coomarasamy (
2. Dr Rajendra Rai (

Trial website

Contact information



Primary contact

Dr Arri Coomarasamy


Contact details

3rd Floor
Academic Department
Birmingham Women's Hospital
Metchley Park Road
B15 2TG
United Kingdom
+44 (0)121 623 6835



Additional contact

Dr Rajendra Rai


Contact details

Department of Obstetrics & Gynaecology
St Mary's Hospital
Mint Wing
South Wharf Road
W2 1PG
United Kingdom
+44 (0)207 886 2475

Additional identifiers

EudraCT number number

Protocol/serial number

HTA 08/38/01

Study information

Scientific title

First trimester progesterone therapy in women with a history of unexplained recurrent miscarriages: a randomised double-blind placebo-controlled multi-centre trial (The PROMISE [PROgesterone in recurrent MIScarriagE] Trial)



Study hypothesis

1. In women with unexplained recurrent miscarriages, progesterone (400 mg pessaries, twice daily), started soon as possible after a positive pregnancy test (and no later than 6 weeks gestation) and continued to 12 weeks of gestation, compared to placebo, increases live births beyond 24 completed weeks by at least 10% (principal objective)
2. Progesterone improves secondary outcomes such as gestation at delivery, on-going pregnancy at 12 weeks, survival at 28 days of neonatal life
3. Progesterone, compared to placebo, does not incur substantial adverse effects to the mother or the neonate
4 Explore differential or subgroup effects of progesterone in prognostic subgroups
5. Perform an economic evaluation for cost-effectiveness

More details can be found at
Protocol can be found at

Ethics approval

REC: West Midlands Research Ethics Committee, 19/10/2009, ref: 09/H1208/44

Study design

Randomised double-blind placebo-controlled multi-centre trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Unexplained recurrent miscarriages


Intervention group: Progesterone pessaries (400 mg twice daily) started soon as possible after a positive pregnancy test (and no later than 6 weeks gestation) and continued to 12 weeks of gestation

Control group: Placebo

Total duration of follow-up per participant: 42 weeks

Intervention type



Not Applicable

Drug names


Primary outcome measures

Live births beyond 24 weeks

Secondary outcome measures

1. Gestation at delivery
2. Clinical pregnancy at 6-8 weeks
3. Ongoing pregnancy at 12 weeks (range 11-13 weeks)
4. Miscarriage rate
5. Survival at 28 days of neonatal life
6. Congenital abnormalities with specific examination for genital anomalies
7. Adverse events

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Women with unexplained recurrent miscarriages (3 or more consecutive first trimester miscarriages)
2. Age 18-39 years at randomisation (likelihood of miscarriages due to chromosomal aberrations is higher in older women; such miscarriages are unlikely to be prevented by progesterone therapy)
3. Spontaneous conception (as confirmed by urinary pregnancy tests)
4. Willing and able to give informed consent

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Inability to conceive spontaneously within 1 year of recruitment
2. Antiphospholipid syndrome (lupus anticoagulant and/or anticardiolipin antibodies [IgG or IgM]); other recognised thrombophilic conditions (testing according to usual clinic practice)
3. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram, or hysteroscopy)
4. Fibroids distorting uterine cavity
5. Abnormal parental karyotype
6. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus (SLE)

Recruitment start date


Recruitment end date



Countries of recruitment

Netherlands, United Kingdom

Trial participating centre

45 hospitals in the UK and the Netherlands

Sponsor information


Imperial College London (UK)

Sponsor details

Clinical Research Governance Office
Sir Alexander Fleming Building
Exhibition Road
United Kingdom
+44 (0)20 7594 1188

Sponsor type




Funder type


Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Publication in the UK NIHR HTA library is anticipated before the end of 2015. Other publications may be produced but are not yet confirmed.

Intention to publish date


Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2015 results in:
2016 results in:

Publication citations

Additional files

Editorial Notes

31/05/2016: Publication reference added. 21/05/2015: the overall trial end date was changed from 01/05/2012 to 01/09/2014.