{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:14:21Z","timestamp":1778811261177,"version":"3.51.4"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T00:00:00Z","timestamp":1463443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1095618"],"award-info":[{"award-number":["OPP1095618"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT094947"],"award-info":[{"award-number":["WT094947"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Health","award":["HICF-T2-0510-007"],"award-info":[{"award-number":["HICF-T2-0510-007"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1186\/s13063-016-1332-2","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T02:56:52Z","timestamp":1463453812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial"],"prefix":"10.1186","volume":"17","author":[{"given":"Haleema","family":"Shakur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Elbourne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zarko","family":"Alfirevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Ronsmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"1332_CR1","volume-title":"Trends in maternal mortality: 1990 to 2010. WHO, UNICEF, UNFPA, and The World Bank estimates","author":"WHO","year":"2012","unstructured":"WHO, UNICEF, UNFPA, The World Bank. Trends in maternal mortality: 1990 to 2010. WHO, UNICEF, UNFPA, and The World Bank estimates. Geneva: World Health Organization; 2012."},{"key":"1332_CR2","doi-asserted-by":"publisher","first-page":"e323","DOI":"10.1016\/S2214-109X(14)70227-X","volume":"2","author":"L Say","year":"2014","unstructured":"Say L, Chou D, Gemmill A, Tun\u00e7alp O, Moller A, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2:e323\u201333.","journal-title":"Lancet Glob Health."},{"key":"1332_CR3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1080\/01443610601016925","volume":"27","author":"J Smith","year":"2007","unstructured":"Smith J, Mousa H. Peripartum hysterectomy for primary post-partum haemorrhage: incidence and maternal morbidity. J Obstet Gynaecol. 2007;27:44\u20137.","journal-title":"J Obstet Gynaecol."},{"issue":"10","key":"1332_CR4","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1002\/bjs.9193","volume":"100","author":"K Ker","year":"2013","unstructured":"Ker K, Prieto-Merino D, Roberts I. Systematic review, meta-analysis and meta-regression of the effect of tranexamic acid on surgical blood loss. Br J Surg. 2013;100(10):1271\u20139.","journal-title":"Br J Surg"},{"key":"1332_CR5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0140-6736(10)60835-5","volume":"376","author":"H Shakur","year":"2010","unstructured":"CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23\u201332.","journal-title":"Lancet"},{"key":"1332_CR6","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/S0140-6736(11)60278-X","volume":"377","author":"I Roberts","year":"2011","unstructured":"CRASH-2 collaborators, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377:1096\u2013101.","journal-title":"Lancet"},{"issue":"2","key":"1332_CR7","doi-asserted-by":"publisher","first-page":"R117s","DOI":"10.1186\/cc10143","volume":"15","author":"AS Ducloy-Bouthors","year":"2011","unstructured":"Ducloy-Bouthors AS, Jude B, Duhamel A, Broisin F, Huissoud C, Keita-Meyer H, et al. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit Care. 2011;15(2):R117s.","journal-title":"Crit Care"},{"issue":"4","key":"1332_CR8","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1093\/bja\/aeu448","volume":"114","author":"L Sentilhes","year":"2015","unstructured":"Sentilhes L, Lasocki S, Ducloy-Bouthors AS, Deruelle P, Dreyfus M, et al. Tranexamic acid for the prevention and treatment of postpartum haemorrhage. Br J Anaesth. 2015;114(4):576\u201387.","journal-title":"Br J Anaesth"},{"key":"1332_CR9","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1745-6215-11-40","volume":"11","author":"H Shakur","year":"2010","unstructured":"Shakur H, Elbourne D, G\u00fclmezoglu M, Alfirevic Z, Ronsmans C, Allen E, et al. The WOMAN trial (world maternal antifibrinolytic trial): tranexamic acid for the treatment of post-partum haemorrhage: an international randomized, double blind placebo controlled trial. Trials. 2010;11:40.","journal-title":"Trials"},{"key":"1332_CR10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1741-7015-8-18","volume":"8","author":"K Schulz","year":"2010","unstructured":"Schulz K, Altman D, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8:18.","journal-title":"BMC Med."},{"issue":"7","key":"1332_CR11","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.jclinepi.2006.10.020","volume":"60","author":"I Ferreira-Gonzalez","year":"2007","unstructured":"Ferreira-Gonzalez I, Permanyer-Miralda G, Busse JW, et al. Methodologic discussions for using and interpreting composite endpoints are limited, but still identify major concerns. J Clin Epidemiol. 2007;60(7):651\u20137. 658-662.","journal-title":"J Clin Epidemiol"},{"issue":"19","key":"1332_CR12","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1001\/jama.289.19.2554","volume":"289","author":"N Freemantle","year":"2003","unstructured":"Freemantle N, Calvert M, Wood J, Eastaugh J, Griffin C. Composite outcomes in randomized trials: greater precision but with greater uncertainty? JAMA. 2003;289(19):2554\u20139.","journal-title":"JAMA"},{"key":"1332_CR13","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1001\/jama.2009.2017","volume":"303","author":"G Tomlinson","year":"2010","unstructured":"Tomlinson G, Detsky A. Composite end points in randomized trials: there is no free lunch. JAMA. 2010;303:267\u20138.","journal-title":"JAMA."},{"key":"1332_CR14","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.thromres.2009.06.034","volume":"1214","author":"A Sawamura","year":"2009","unstructured":"Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res. 2009;1214:608\u201313.","journal-title":"Thromb Res."},{"key":"1332_CR15","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.tcm.2005.09.005","volume":"15","author":"CJ Lowenstein","year":"2005","unstructured":"Lowenstein CJ, Morrell CN, Yamakuchi M. Regulation of Weibel-Palade body exocytosis. Trends Cardiovasc Med. 2005;15:302\u20138.","journal-title":"Trends Cardiovasc Med."},{"issue":"1","key":"1332_CR16","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13054-015-0735-x","volume":"19","author":"S Gando","year":"2015","unstructured":"Gando S, Otomo Y. Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. Crit Care. 2015;19(1):72.","journal-title":"Crit Care"},{"key":"1332_CR17","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1182\/blood.V69.2.460.460","volume":"69","author":"E Kruithof","year":"1987","unstructured":"Kruithof E, Tran-Thang C, Gudinchet A, Hauert J, Nicoloso G, Genton C, et al. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood. 1987;69:460\u20136.","journal-title":"Blood."},{"key":"1332_CR18","doi-asserted-by":"publisher","first-page":"449.e1","DOI":"10.1016\/j.ajog.2013.07.007","volume":"209","author":"MS Kramer","year":"2013","unstructured":"Kramer MS, Berg C, Abenhaim H, Dahhou M, Rouleau J, Mehrabadi A, et al. Incidence, risk factors, and temporal trends in severe post-partum hemorrhage. Am J Obstet Gynecol. 2013;209:449.e1\u20137.","journal-title":"Am J Obstet Gynecol"},{"key":"1332_CR19","volume-title":"WHO guidelines for the management of post-partum haemorrhage and retained placenta","author":"World Health Organization","year":"2009","unstructured":"World Health Organization. WHO guidelines for the management of post-partum haemorrhage and retained placenta. Geneva: World Health Organization; 2009."},{"issue":"5","key":"1332_CR20","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1097\/AOG.0000000000000230","volume":"123","author":"NK Tepper","year":"2014","unstructured":"Tepper NK, Boulet SL, Whiteman MK, Monsour M, Marchbanks PA, Hooper WC, et al. Post-partum venous thromboembolism: incidence and risk factors. Obstet Gynecol. 2014;123(5):987\u201396.","journal-title":"Obstet Gynecol"},{"key":"1332_CR21","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1111\/j.1538-7836.2008.02921.x","volume":"6","author":"ER Pomp","year":"2008","unstructured":"Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the post-partum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost. 2008;6:632\u20137.","journal-title":"J Thromb Haemost."},{"key":"1332_CR22","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1046\/j.1471-0528.2003.02151.x","volume":"110","author":"M Waterstone","year":"2003","unstructured":"Waterstone M, Wolfe C, Hooper R, Bewley S. Postnatal morbidity after childbirth and severe obstetric morbidity. BJOG-Int J Obstet Gy. 2003;110:128\u201333.","journal-title":"BJOG-Int J Obstet Gy."},{"key":"1332_CR23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","volume":"16","author":"EuroQol Group","year":"1990","unstructured":"EuroQol Group. EuroQol \u2013 a new facility for the measurement of health-related quality of life. Health Pol. 1990;16:199\u2013208.","journal-title":"Health Pol."},{"key":"1332_CR24","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1213\/ANE.0b013e3181c92b23","volume":"110","author":"JM Murkin","year":"2010","unstructured":"Murkin JM, Falter F, Granton J, Young B, Burt C, Chu M. High-dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg. 2010;110:350\u20133.","journal-title":"Anesth Analg."},{"key":"1332_CR25","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1124\/jpet.301.1.168","volume":"301","author":"R Furtm\u00fcller","year":"2002","unstructured":"Furtm\u00fcller R, Schlag MG, Berger M, Hopf R, Huck S, Sieghart W, et al. Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid (A) receptor antagonistic effect. J Pharmacol Exp Ther. 2002;301:168\u201373.","journal-title":"J Pharmacol Exp Ther."},{"key":"1332_CR26","volume-title":"International Conference on Harmonisation (ICH) harmonised tripartite guideline: guideline for good clinical practice (GCP)","author":"ICH","year":"1996","unstructured":"ICH. International Conference on Harmonisation (ICH) harmonised tripartite guideline: guideline for good clinical practice (GCP). Geneva: ICH; 1996."},{"key":"1332_CR27","unstructured":"MedDRA\u00ae the Medical Dictionary for Regulatory Activities terminology is the international medical terminology developed under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). \n                    www.meddra.org\n                    \n                   Accessed 11 May 2016."},{"key":"1332_CR28","unstructured":"Summary of Product Characteristics for Tranexamic Acid 100\u00a0mg\/ml Solution for Injection. \n                    https:\/\/www.medicines.org.uk\/emc\/medicine\/28163\n                    \n                   (Accessed 15 Sept 2015)."},{"issue":"19","key":"1332_CR29","doi-asserted-by":"publisher","first-page":"2917","DOI":"10.1002\/sim.1296","volume":"21","author":"SJ Pocock","year":"2002","unstructured":"Pocock SJ, Assmann SE, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat Med. 2002;21(19):2917\u201330.","journal-title":"Stat Med"},{"key":"1332_CR30","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/1745-6215-15-139","volume":"15","author":"B Kahan","year":"2014","unstructured":"Kahan B, Jairath V, Dor\u00e9 C, Morris T. The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies. Trials. 2014;15:139.","journal-title":"Trials."},{"issue":"7","key":"1332_CR31","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1002\/sim.1981","volume":"24","author":"IR White","year":"2005","unstructured":"White IR, Thompson SG. Adjusting for partially missing baseline measurements in randomized trials. Stat Med. 2005;24(7):993\u20131007.","journal-title":"Stat Med"},{"key":"1332_CR32","first-page":"164","volume":"1","author":"DL Sackett","year":"1996","unstructured":"Sackett DL, Deeks JJ, Altman D. Down with odds ratios! Evid-Based Med. 1996;1:164\u20137.","journal-title":"Evid-Based Med."},{"issue":"526","key":"1332_CR33","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1259\/0007-1285-44-526-793","volume":"44","author":"JL Haybittle","year":"1971","unstructured":"Haybittle JL. Repeated assessment of results in clinical trials of cancer treatment. Br J Radiol. 1971;44(526):793\u20137.","journal-title":"Br J Radiol"},{"issue":"1","key":"1332_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/bjc.1977.1","volume":"35","author":"R Peto","year":"1977","unstructured":"Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977;35(1):1\u201339.","journal-title":"Br J Cancer"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-016-1332-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13063-016-1332-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-016-1332-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-016-1332-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T10:58:03Z","timestamp":1589540283000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-016-1332-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,17]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["1332"],"URL":"https:\/\/doi.org\/10.1186\/s13063-016-1332-2","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,17]]},"assertion":[{"value":"29 September 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"249"}}