Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial
Background: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. Methods:...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
World Scientific Publishing
2022-09-01
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| Series: | Fertility & Reproduction |
| Online Access: | https://www.worldscientific.com/doi/10.1142/S2661318222740115 |
| _version_ | 1798023308607750144 |
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| author | Charlotte HAMEL Sjors COPPUS Joyce VAN DEN BERG Esther HINK Jacoba VAN SEETERS Paul VAN KESTEREN Ashley MERIEN Bas TORRENGA Rafli VAN DE LAAR Josien Terwisscha VAN SCHELTINGA Ingrid GAUGLER-SENDEN Peppino GRAZIOSI Minouche VAN RUMSTE Ewka NELISSEN Frank VANDENBUSSCHE Marcus SNIJDERS |
| author_facet | Charlotte HAMEL Sjors COPPUS Joyce VAN DEN BERG Esther HINK Jacoba VAN SEETERS Paul VAN KESTEREN Ashley MERIEN Bas TORRENGA Rafli VAN DE LAAR Josien Terwisscha VAN SCHELTINGA Ingrid GAUGLER-SENDEN Peppino GRAZIOSI Minouche VAN RUMSTE Ewka NELISSEN Frank VANDENBUSSCHE Marcus SNIJDERS |
| author_sort | Charlotte HAMEL |
| collection | DOAJ |
| description | Background: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. Methods: This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 mg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 68 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. Findings: Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79.1%) of 172 participants reached complete evacuation compared to 101 (58.7%) of 172 participants in the placebo group (p<0.0001, RR 1.35, 95% CI 1.16-1.56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0.0005). Interpretation: Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL. |
| first_indexed | 2024-04-11T17:44:09Z |
| format | Article |
| id | doaj.art-364b2f9949c94503b41dff15584af1bc |
| institution | Directory Open Access Journal |
| issn | 2661-3182 2661-3174 |
| language | English |
| last_indexed | 2024-04-11T17:44:09Z |
| publishDate | 2022-09-01 |
| publisher | World Scientific Publishing |
| record_format | Article |
| series | Fertility & Reproduction |
| spelling | doaj.art-364b2f9949c94503b41dff15584af1bc2022-12-22T04:11:24ZengWorld Scientific PublishingFertility & Reproduction2661-31822661-31742022-09-010403n04999910.1142/S2661318222740115Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised TrialCharlotte HAMEL0Sjors COPPUS1Joyce VAN DEN BERG2Esther HINK3Jacoba VAN SEETERS4Paul VAN KESTEREN5Ashley MERIEN6Bas TORRENGA7Rafli VAN DE LAAR8Josien Terwisscha VAN SCHELTINGA9Ingrid GAUGLER-SENDEN10Peppino GRAZIOSI11Minouche VAN RUMSTE12Ewka NELISSEN13Frank VANDENBUSSCHE14Marcus SNIJDERS15Department of Obstetrics and Gynaecology, Canisius Wilhelmina Hospital, Nijmegen, the NetherlandsDepartment of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, the NetherlandsDepartment of Obstetrics and Gynaecology, Gelderse Vallei Hospital, Ede, the NetherlandsDepartment of Obstetrics and Gynaecology, Radboud university medical centre, Nijmegen, the NetherlandsDepartment of Obstetrics and Gynaecology, Amphia Hospital, Breda, the NetherlandsDepartment of Obstetrics and Gynaecology, OLVG, the NetherlandsDepartment of Obstetrics and Gynaecology, Rijnstate, Arnhem, the NetherlandsDepartment of Obstetrics and Gynaecology, Ikazia Hospital, the NetherlandsDepartment of Obstetrics and Gynaecology, Vie Curi Medical Centre, the NetherlandsDepartment of Obstetrics and Gynaecology, Maasstad Hospital, Rotterdam, the NetherlandsDepartment of Obstetrics and Gynaecology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, the NetherlandsDepartment of Obstetrics and Gynaecology, St. Antonius Hospital, Nieuwegein, the NetherlandsDepartment of Obstetrics and Gynaecology, Catharina Hospital, Eindhoven, the NetherlandsDepartment of Obstetrics and Gynaecology, Laurentius Hospital, Roermond, the NetherlandsDepartment of Obstetrics and Gynaecology, Radboud university medical centre, Nijmegen, the NetherlandsDepartment of Obstetrics and Gynaecology, Canisius Wilhelmina Hospital, Nijmegen, the NetherlandsBackground: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. Methods: This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 mg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 68 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. Findings: Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79.1%) of 172 participants reached complete evacuation compared to 101 (58.7%) of 172 participants in the placebo group (p<0.0001, RR 1.35, 95% CI 1.16-1.56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0.0005). Interpretation: Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL.https://www.worldscientific.com/doi/10.1142/S2661318222740115 |
| spellingShingle | Charlotte HAMEL Sjors COPPUS Joyce VAN DEN BERG Esther HINK Jacoba VAN SEETERS Paul VAN KESTEREN Ashley MERIEN Bas TORRENGA Rafli VAN DE LAAR Josien Terwisscha VAN SCHELTINGA Ingrid GAUGLER-SENDEN Peppino GRAZIOSI Minouche VAN RUMSTE Ewka NELISSEN Frank VANDENBUSSCHE Marcus SNIJDERS Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial Fertility & Reproduction |
| title | Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial |
| title_full | Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial |
| title_fullStr | Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial |
| title_full_unstemmed | Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial |
| title_short | Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial |
| title_sort | mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss the triple m trial a double blind placebo controlled randomised trial |
| url | https://www.worldscientific.com/doi/10.1142/S2661318222740115 |
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