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PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

Coomarasamy, Arri and Williams, Helen and Truchanowicz, Ewa and Seed, Paul T and Small, Rachel and Quenby, Siobhan and Gupta, Pratima and Dawood, Feroza and Koot, Yvonne E and Atik, Ruth Bender and Bloemenkamp, Kitty Wm and Brady, Rebecca and Briley, Annette and Cavallaro, Rebecca and Cheong, Ying C and Chu, Justin and Eapen, Abey and Essex, Holly and Ewies, Ayman and Hoek, Annemieke and Kaaijk, Eugenie M and Koks, Carolien A and Li, Tin-Chiu and MacLean, Marjory and Mol, Ben W and Moore, Judith and Parrott, Steve and Ross, Jackie A and Sharpe, Lisa and Stewart, Jane and Trépel, Dominic and Vaithilingam, Nirmala and Farquharson, Roy G and Kilby, Mark David and Khalaf, Yacoub and Goddijn, Mariëtte and Regan, Lesley and Rai, Rajendra (2016) PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation. Health technology assessment (Winchester, England), 20 (41). pp. 1-92. ISSN 2046-4924.

Full text not available from this repository.
Official URL: https://www.journalslibrary.nihr.ac.uk/hta/hta2041...

Abstract

BACKGROUND AND OBJECTIVES

Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted.

DESIGN AND SETTING

A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites).

PARTICIPANTS AND INTERVENTIONS

Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks).

MAIN OUTCOME MEASURES

Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use.

METHODS

Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth.

RESULTS

A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341.

CONCLUSIONS

There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM.

LIMITATIONS

This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle.

FUTURE WORK

Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44.

FUNDING

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

Item Type: Article
Subjects: WP Gynaecology. Women’s health
WQ Obstetrics. Midwifery
Divisions: Womens and Childrens > Gynaecology
Womens and Childrens > Obstetrics
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Depositing User: Preeti Puligari
Date Deposited: 30 Mar 2017 12:47
Last Modified: 30 Mar 2017 12:47
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1317

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