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

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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, Aravinthan; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne; Bender Atik, Ruth; Bloemenkamp, Kitty Wm; Brady, Rebecca; Briley, Annette; Cavallaro, Rebecca; Cheong, Ying; Chu, Justin; Eapen, Abey; Essex, Holly; Ewies, Ayman; Hoek, Annemieke; Kaaijk, EM; Koks, Carolien Am; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben Willem; Moore, Judith; Parrott, Steve; Ross, Jackie; Sharpe, Lisa; Stewart, Jane; Trepel, Dominic; Vaithilingam, Nirmala; Farquharson, RG; Kilby, Mark; Khalaf, Yacoub; Goddijn, Mariëtte; Regan, Lesley; Rai, Raj.

In: Health Technology Assessment, 05.2016.

Research output: Contribution to journalArticlepeer-review

Harvard

Coomarasamy, A, Williams, H, Truchanowicz, E, Seed, PT, Small, R, Quenby, S, Gupta, P, Dawood, F, Koot, Y, Bender Atik, R, Bloemenkamp, KW, Brady, R, Briley, A, Cavallaro, R, Cheong, Y, Chu, J, Eapen, A, Essex, H, Ewies, A, Hoek, A, Kaaijk, EM, Koks, CA, Li, T-C, MacLean, M, Mol, BW, Moore, J, Parrott, S, Ross, J, Sharpe, L, Stewart, J, Trepel, D, Vaithilingam, N, Farquharson, RG, Kilby, M, Khalaf, Y, Goddijn, M, Regan, L & Rai, R 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. https://doi.org/10.3310/hta20410

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Coomarasamy, Aravinthan ; Williams, Helen ; Truchanowicz, Ewa ; Seed, Paul T ; Small, Rachel ; Quenby, Siobhan ; Gupta, Pratima ; Dawood, Feroza ; Koot, Yvonne ; Bender Atik, Ruth ; Bloemenkamp, Kitty Wm ; Brady, Rebecca ; Briley, Annette ; Cavallaro, Rebecca ; Cheong, Ying ; Chu, Justin ; Eapen, Abey ; Essex, Holly ; Ewies, Ayman ; Hoek, Annemieke ; Kaaijk, EM ; Koks, Carolien Am ; Li, Tin-Chiu ; MacLean, Marjory ; Mol, Ben Willem ; Moore, Judith ; Parrott, Steve ; Ross, Jackie ; Sharpe, Lisa ; Stewart, Jane ; Trepel, Dominic ; Vaithilingam, Nirmala ; Farquharson, RG ; Kilby, Mark ; Khalaf, Yacoub ; Goddijn, Mariëtte ; Regan, Lesley ; Rai, Raj. / 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. In: Health Technology Assessment. 2016.

Bibtex

@article{f0989bd3ea524b759b0a6fb902ea7dcd,
title = "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",
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{\textregistered}, 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{\textquoteright}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.",
author = "Aravinthan Coomarasamy and Helen Williams and Ewa Truchanowicz and Seed, {Paul T} and Rachel Small and Siobhan Quenby and Pratima Gupta and Feroza Dawood and Yvonne Koot and {Bender Atik}, Ruth and Bloemenkamp, {Kitty Wm} and Rebecca Brady and Annette Briley and Rebecca Cavallaro and Ying Cheong and Justin Chu and Abey Eapen and Holly Essex and Ayman Ewies and Annemieke Hoek and EM Kaaijk and Koks, {Carolien Am} and Tin-Chiu Li and Marjory MacLean and Mol, {Ben Willem} and Judith Moore and Steve Parrott and Jackie Ross and Lisa Sharpe and Jane Stewart and Dominic Trepel and Nirmala Vaithilingam and RG Farquharson and Mark Kilby and Yacoub Khalaf and Mari{\"e}tte Goddijn and Lesley Regan and Raj Rai",
year = "2016",
month = may,
doi = "10.3310/hta20410",
language = "English",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "NIHR Health Technology Assessment Programme",

}

RIS

TY - JOUR

T1 - PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages

T2 - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation

AU - Coomarasamy, Aravinthan

AU - Williams, Helen

AU - Truchanowicz, Ewa

AU - Seed, Paul T

AU - Small, Rachel

AU - Quenby, Siobhan

AU - Gupta, Pratima

AU - Dawood, Feroza

AU - Koot, Yvonne

AU - Bender Atik, Ruth

AU - Bloemenkamp, Kitty Wm

AU - Brady, Rebecca

AU - Briley, Annette

AU - Cavallaro, Rebecca

AU - Cheong, Ying

AU - Chu, Justin

AU - Eapen, Abey

AU - Essex, Holly

AU - Ewies, Ayman

AU - Hoek, Annemieke

AU - Kaaijk, EM

AU - Koks, Carolien Am

AU - Li, Tin-Chiu

AU - MacLean, Marjory

AU - Mol, Ben Willem

AU - Moore, Judith

AU - Parrott, Steve

AU - Ross, Jackie

AU - Sharpe, Lisa

AU - Stewart, Jane

AU - Trepel, Dominic

AU - Vaithilingam, Nirmala

AU - Farquharson, RG

AU - Kilby, Mark

AU - Khalaf, Yacoub

AU - Goddijn, Mariëtte

AU - Regan, Lesley

AU - Rai, Raj

PY - 2016/5

Y1 - 2016/5

N2 - 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.

AB - 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.

U2 - 10.3310/hta20410

DO - 10.3310/hta20410

M3 - Article

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

ER -