Progesterone to prevent miscarriage in women with early pregnancy bleeding: The PRISM RCT

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Progesterone to prevent miscarriage in women with early pregnancy bleeding : The PRISM RCT. / Coomarasamy, Arri; Harb, Hoda M.; Devall, Adam J.; Cheed, Versha; Roberts, Tracy E.; Goranitis, Ilias; Ogwulu, Chidubem B.; Williams, Helen M.; Gallos, Ioannis D.; Eapen, Abey; Daniels, Jane P.; Ahmed, Amna; Bender-Atik, Ruth; Bhatia, Kalsang; Bottomley, Cecilia; Brewin, Jane; Choudhary, Meenakshi; Crosfill, Fiona; Deb, Shilpa; Duncan, W. Colin; Ewer, Andrew; Hinshaw, Kim; Holland, Thomas; Izzat, Feras; Johns, Jemma; Lumsden, Mary Ann; Manda, Padma; Norman, Jane E.; Nunes, Natalie; Overton, Caroline E.; Kriedt, Kathiuska; Quenby, Siobhan; Rao, Sandhya; Ross, Jackie; Shahid, Anupama; Underwood, Martyn; Vaithilingham, Nirmala; Watkins, Linda; Wykes, Catherine; Horne, Andrew W.; Jurkovic, Davor; Middleton, Lee J.

In: Health Technology Assessment, Vol. 24, No. 33, 06.2020, p. 1-70.

Research output: Contribution to journalArticlepeer-review

Harvard

Coomarasamy, A, Harb, HM, Devall, AJ, Cheed, V, Roberts, TE, Goranitis, I, Ogwulu, CB, Williams, HM, Gallos, ID, Eapen, A, Daniels, JP, Ahmed, A, Bender-Atik, R, Bhatia, K, Bottomley, C, Brewin, J, Choudhary, M, Crosfill, F, Deb, S, Duncan, WC, Ewer, A, Hinshaw, K, Holland, T, Izzat, F, Johns, J, Lumsden, MA, Manda, P, Norman, JE, Nunes, N, Overton, CE, Kriedt, K, Quenby, S, Rao, S, Ross, J, Shahid, A, Underwood, M, Vaithilingham, N, Watkins, L, Wykes, C, Horne, AW, Jurkovic, D & Middleton, LJ 2020, 'Progesterone to prevent miscarriage in women with early pregnancy bleeding: The PRISM RCT', Health Technology Assessment, vol. 24, no. 33, pp. 1-70. https://doi.org/10.3310/hta24330

APA

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Author

Coomarasamy, Arri ; Harb, Hoda M. ; Devall, Adam J. ; Cheed, Versha ; Roberts, Tracy E. ; Goranitis, Ilias ; Ogwulu, Chidubem B. ; Williams, Helen M. ; Gallos, Ioannis D. ; Eapen, Abey ; Daniels, Jane P. ; Ahmed, Amna ; Bender-Atik, Ruth ; Bhatia, Kalsang ; Bottomley, Cecilia ; Brewin, Jane ; Choudhary, Meenakshi ; Crosfill, Fiona ; Deb, Shilpa ; Duncan, W. Colin ; Ewer, Andrew ; Hinshaw, Kim ; Holland, Thomas ; Izzat, Feras ; Johns, Jemma ; Lumsden, Mary Ann ; Manda, Padma ; Norman, Jane E. ; Nunes, Natalie ; Overton, Caroline E. ; Kriedt, Kathiuska ; Quenby, Siobhan ; Rao, Sandhya ; Ross, Jackie ; Shahid, Anupama ; Underwood, Martyn ; Vaithilingham, Nirmala ; Watkins, Linda ; Wykes, Catherine ; Horne, Andrew W. ; Jurkovic, Davor ; Middleton, Lee J. / Progesterone to prevent miscarriage in women with early pregnancy bleeding : The PRISM RCT. In: Health Technology Assessment. 2020 ; Vol. 24, No. 33. pp. 1-70.

Bibtex

@article{6ee5bf5d671b4fb487022eeea0897ea9,
title = "Progesterone to prevent miscarriage in women with early pregnancy bleeding: The PRISM RCT",
abstract = "Background: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. Objectives: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. Design: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. Setting: A total of 48 hospitals in the UK. Participants: Women aged 16–39 years with early pregnancy bleeding. Interventions: Women aged 16–39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. Main outcome measures: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. Results: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval –£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.",
author = "Arri Coomarasamy and Harb, {Hoda M.} and Devall, {Adam J.} and Versha Cheed and Roberts, {Tracy E.} and Ilias Goranitis and Ogwulu, {Chidubem B.} and Williams, {Helen M.} and Gallos, {Ioannis D.} and Abey Eapen and Daniels, {Jane P.} and Amna Ahmed and Ruth Bender-Atik and Kalsang Bhatia and Cecilia Bottomley and Jane Brewin and Meenakshi Choudhary and Fiona Crosfill and Shilpa Deb and Duncan, {W. Colin} and Andrew Ewer and Kim Hinshaw and Thomas Holland and Feras Izzat and Jemma Johns and Lumsden, {Mary Ann} and Padma Manda and Norman, {Jane E.} and Natalie Nunes and Overton, {Caroline E.} and Kathiuska Kriedt and Siobhan Quenby and Sandhya Rao and Jackie Ross and Anupama Shahid and Martyn Underwood and Nirmala Vaithilingham and Linda Watkins and Catherine Wykes and Horne, {Andrew W.} and Davor Jurkovic and Middleton, {Lee J.}",
note = "Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 12/167/26. The contractual start date was in October 2014. The draft report began editorial review in October 2018 and was accepted for publication in May 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors{\textquoteright} report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Funding Information: This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. Funding Information: 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. 24, No. 33. See the NIHR Journals Library website for further project information. Funding Information: 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. 24, No. 33. See the NIHR Journals Library website for further project information. Funding Information: l The study is supported by the Miscarriage Association (a patient support organisation), The Scottish Early Pregnancy Network, INVOLVE (a national advisory group that supports greater public involvement in health research), PRIME (Public and Researchers Involvement in Maternity and Early Pregnancy), CHARM (Charity for Research into Miscarriage) and Tommy{\textquoteright}s charity. Publisher Copyright: {\textcopyright} Queen{\textquoteright}s Printer and Controller of HMSO 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jun,
doi = "10.3310/hta24330",
language = "English",
volume = "24",
pages = "1--70",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "NIHR Health Technology Assessment Programme",
number = "33",

}

RIS

TY - JOUR

T1 - Progesterone to prevent miscarriage in women with early pregnancy bleeding

T2 - The PRISM RCT

AU - Coomarasamy, Arri

AU - Harb, Hoda M.

AU - Devall, Adam J.

AU - Cheed, Versha

AU - Roberts, Tracy E.

AU - Goranitis, Ilias

AU - Ogwulu, Chidubem B.

AU - Williams, Helen M.

AU - Gallos, Ioannis D.

AU - Eapen, Abey

AU - Daniels, Jane P.

AU - Ahmed, Amna

AU - Bender-Atik, Ruth

AU - Bhatia, Kalsang

AU - Bottomley, Cecilia

AU - Brewin, Jane

AU - Choudhary, Meenakshi

AU - Crosfill, Fiona

AU - Deb, Shilpa

AU - Duncan, W. Colin

AU - Ewer, Andrew

AU - Hinshaw, Kim

AU - Holland, Thomas

AU - Izzat, Feras

AU - Johns, Jemma

AU - Lumsden, Mary Ann

AU - Manda, Padma

AU - Norman, Jane E.

AU - Nunes, Natalie

AU - Overton, Caroline E.

AU - Kriedt, Kathiuska

AU - Quenby, Siobhan

AU - Rao, Sandhya

AU - Ross, Jackie

AU - Shahid, Anupama

AU - Underwood, Martyn

AU - Vaithilingham, Nirmala

AU - Watkins, Linda

AU - Wykes, Catherine

AU - Horne, Andrew W.

AU - Jurkovic, Davor

AU - Middleton, Lee J.

N1 - Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 12/167/26. The contractual start date was in October 2014. The draft report began editorial review in October 2018 and was accepted for publication in May 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Funding Information: This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. Funding Information: 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. 24, No. 33. See the NIHR Journals Library website for further project information. Funding Information: 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. 24, No. 33. See the NIHR Journals Library website for further project information. Funding Information: l The study is supported by the Miscarriage Association (a patient support organisation), The Scottish Early Pregnancy Network, INVOLVE (a national advisory group that supports greater public involvement in health research), PRIME (Public and Researchers Involvement in Maternity and Early Pregnancy), CHARM (Charity for Research into Miscarriage) and Tommy’s charity. Publisher Copyright: © Queen’s Printer and Controller of HMSO 2020. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/6

Y1 - 2020/6

N2 - Background: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. Objectives: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. Design: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. Setting: A total of 48 hospitals in the UK. Participants: Women aged 16–39 years with early pregnancy bleeding. Interventions: Women aged 16–39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. Main outcome measures: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. Results: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval –£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.

AB - Background: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. Objectives: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. Design: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. Setting: A total of 48 hospitals in the UK. Participants: Women aged 16–39 years with early pregnancy bleeding. Interventions: Women aged 16–39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. Main outcome measures: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. Results: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval –£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. Conclusions: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets.

UR - http://www.scopus.com/inward/record.url?scp=85087531478&partnerID=8YFLogxK

U2 - 10.3310/hta24330

DO - 10.3310/hta24330

M3 - Article

C2 - 32609084

AN - SCOPUS:85087531478

VL - 24

SP - 1

EP - 70

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 33

ER -