Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: The Quadruple P randomised controlled trial

Maud D. van Zijl, Bouchra Koullali, Christiana A. Naaktgeboren, Ewoud Schuit, Dick J. Bekedam, Etelka Moll, Martijn A. Oudijk, Wilhelmina M. van Baal, Marjon A. de Boer, Henricus Visser, Joris van Drongelen, Flip W. van de Made, Karlijn C. Vollebregt, Moira A. Muller, Mireille N. Bekker, Jozien T.J. Brons, Marieke Sueters, Josje Langenveld, Maureen T. Franssen, Nico W. Schuitemaker & 11 others Erik van Beek, Hubertina C.J. Scheepers, Karin de Boer, Eveline M. Tepe, Anjoke J.M. Huisjes, Angelo B. Hooker, Evelyn C.J. Verheijen, Dimitri N. Papatsonis, Ben Willem J. Mol, Brenda M. Kazemier, Eva Pajkrt

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. Methods/design: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. Discussion: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. Trial registration: Trial registration number: NTR 4414. Date of registration January 29th 2014.

Original languageEnglish
Article number284
JournalBMC Pregnancy and Childbirth
Volume17
Issue number1
DOIs
Publication statusPublished - 4 Sep 2017

Cite this

van Zijl, Maud D. ; Koullali, Bouchra ; Naaktgeboren, Christiana A. ; Schuit, Ewoud ; Bekedam, Dick J. ; Moll, Etelka ; Oudijk, Martijn A. ; van Baal, Wilhelmina M. ; de Boer, Marjon A. ; Visser, Henricus ; van Drongelen, Joris ; van de Made, Flip W. ; Vollebregt, Karlijn C. ; Muller, Moira A. ; Bekker, Mireille N. ; Brons, Jozien T.J. ; Sueters, Marieke ; Langenveld, Josje ; Franssen, Maureen T. ; Schuitemaker, Nico W. ; van Beek, Erik ; Scheepers, Hubertina C.J. ; de Boer, Karin ; Tepe, Eveline M. ; Huisjes, Anjoke J.M. ; Hooker, Angelo B. ; Verheijen, Evelyn C.J. ; Papatsonis, Dimitri N. ; Mol, Ben Willem J. ; Kazemier, Brenda M. ; Pajkrt, Eva. / Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length : The Quadruple P randomised controlled trial. In: BMC Pregnancy and Childbirth. 2017 ; Vol. 17, No. 1.
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abstract = "Background: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. Methods/design: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. Discussion: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. Trial registration: Trial registration number: NTR 4414. Date of registration January 29th 2014.",
keywords = "Multiples, Pessary, Preterm birth, Prevention, Progesterone, Singletons",
author = "{van Zijl}, {Maud D.} and Bouchra Koullali and Naaktgeboren, {Christiana A.} and Ewoud Schuit and Bekedam, {Dick J.} and Etelka Moll and Oudijk, {Martijn A.} and {van Baal}, {Wilhelmina M.} and {de Boer}, {Marjon A.} and Henricus Visser and {van Drongelen}, Joris and {van de Made}, {Flip W.} and Vollebregt, {Karlijn C.} and Muller, {Moira A.} and Bekker, {Mireille N.} and Brons, {Jozien T.J.} and Marieke Sueters and Josje Langenveld and Franssen, {Maureen T.} and Schuitemaker, {Nico W.} and {van Beek}, Erik and Scheepers, {Hubertina C.J.} and {de Boer}, Karin and Tepe, {Eveline M.} and Huisjes, {Anjoke J.M.} and Hooker, {Angelo B.} and Verheijen, {Evelyn C.J.} and Papatsonis, {Dimitri N.} and Mol, {Ben Willem J.} and Kazemier, {Brenda M.} and Eva Pajkrt",
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van Zijl, MD, Koullali, B, Naaktgeboren, CA, Schuit, E, Bekedam, DJ, Moll, E, Oudijk, MA, van Baal, WM, de Boer, MA, Visser, H, van Drongelen, J, van de Made, FW, Vollebregt, KC, Muller, MA, Bekker, MN, Brons, JTJ, Sueters, M, Langenveld, J, Franssen, MT, Schuitemaker, NW, van Beek, E, Scheepers, HCJ, de Boer, K, Tepe, EM, Huisjes, AJM, Hooker, AB, Verheijen, ECJ, Papatsonis, DN, Mol, BWJ, Kazemier, BM & Pajkrt, E 2017, 'Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: The Quadruple P randomised controlled trial' BMC Pregnancy and Childbirth, vol. 17, no. 1, 284. https://doi.org/10.1186/s12884-017-1454-x

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length : The Quadruple P randomised controlled trial. / van Zijl, Maud D.; Koullali, Bouchra; Naaktgeboren, Christiana A.; Schuit, Ewoud; Bekedam, Dick J.; Moll, Etelka; Oudijk, Martijn A.; van Baal, Wilhelmina M.; de Boer, Marjon A.; Visser, Henricus; van Drongelen, Joris; van de Made, Flip W.; Vollebregt, Karlijn C.; Muller, Moira A.; Bekker, Mireille N.; Brons, Jozien T.J.; Sueters, Marieke; Langenveld, Josje; Franssen, Maureen T.; Schuitemaker, Nico W.; van Beek, Erik; Scheepers, Hubertina C.J.; de Boer, Karin; Tepe, Eveline M.; Huisjes, Anjoke J.M.; Hooker, Angelo B.; Verheijen, Evelyn C.J.; Papatsonis, Dimitri N.; Mol, Ben Willem J.; Kazemier, Brenda M.; Pajkrt, Eva.

In: BMC Pregnancy and Childbirth, Vol. 17, No. 1, 284, 04.09.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length

T2 - The Quadruple P randomised controlled trial

AU - van Zijl, Maud D.

AU - Koullali, Bouchra

AU - Naaktgeboren, Christiana A.

AU - Schuit, Ewoud

AU - Bekedam, Dick J.

AU - Moll, Etelka

AU - Oudijk, Martijn A.

AU - van Baal, Wilhelmina M.

AU - de Boer, Marjon A.

AU - Visser, Henricus

AU - van Drongelen, Joris

AU - van de Made, Flip W.

AU - Vollebregt, Karlijn C.

AU - Muller, Moira A.

AU - Bekker, Mireille N.

AU - Brons, Jozien T.J.

AU - Sueters, Marieke

AU - Langenveld, Josje

AU - Franssen, Maureen T.

AU - Schuitemaker, Nico W.

AU - van Beek, Erik

AU - Scheepers, Hubertina C.J.

AU - de Boer, Karin

AU - Tepe, Eveline M.

AU - Huisjes, Anjoke J.M.

AU - Hooker, Angelo B.

AU - Verheijen, Evelyn C.J.

AU - Papatsonis, Dimitri N.

AU - Mol, Ben Willem J.

AU - Kazemier, Brenda M.

AU - Pajkrt, Eva

PY - 2017/9/4

Y1 - 2017/9/4

N2 - Background: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. Methods/design: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. Discussion: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. Trial registration: Trial registration number: NTR 4414. Date of registration January 29th 2014.

AB - Background: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. Methods/design: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. Discussion: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. Trial registration: Trial registration number: NTR 4414. Date of registration January 29th 2014.

KW - Multiples

KW - Pessary

KW - Preterm birth

KW - Prevention

KW - Progesterone

KW - Singletons

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U2 - 10.1186/s12884-017-1454-x

DO - 10.1186/s12884-017-1454-x

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VL - 17

JO - BMC Pregnancy and Childbirth

JF - BMC Pregnancy and Childbirth

SN - 1471-2393

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ER -