STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): An international consortium of randomised placebo-controlled trials

A. Pels, L. C. Kenny, Z. Alfirevic, P. N. Baker, P. von Dadelszen, C. Gluud, C. T. Kariya, B. W. Mol, A. Papageorghiou, A. G. van Wassenaer-Leemhuis, W. Ganzevoort, K. M. Groom, L. M. McCowan, P. R. Stone, A. Lee, L. Mackay, C. Oyston, G. Gardener, A. Khashan, J. Eustace & 31 others E. Dempsey, R. Jackson, J. Dickinson, A. Gill, P. Muller, R. Sekar, R. A. Reid, J. Unterschneider, A. Welsh, J. Marlow, Jon Hyett, S. Walker, J. Morris, D. Watson, C. McKinlay, S. Harris, K. I. Lim, S. Lalji, L. A. Magee, T. Lee, J. Li, A. Hutfield, M. Ansermino, W. Robinson, J. Singer, A. R. Synnes, J. Burrows, F. Audibert, E. Bujold, B. Piedboeuf, international STRIDER Consortium

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis.

LanguageEnglish
Article number440
JournalBMC Pregnancy and Childbirth
Volume17
Issue number1
DOIs
Publication statusPublished - 28 Dec 2017

Keywords

  • Fetal growth restriction
  • Neonatal morbidity
  • Neonatal mortality
  • Placental insufficiency
  • Randomised placebo controlled trial
  • Sildenafil

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Pels, A. ; Kenny, L. C. ; Alfirevic, Z. ; Baker, P. N. ; von Dadelszen, P. ; Gluud, C. ; Kariya, C. T. ; Mol, B. W. ; Papageorghiou, A. ; van Wassenaer-Leemhuis, A. G. ; Ganzevoort, W. ; Groom, K. M. ; McCowan, L. M. ; Stone, P. R. ; Lee, A. ; Mackay, L. ; Oyston, C. ; Gardener, G. ; Khashan, A. ; Eustace, J. ; Dempsey, E. ; Jackson, R. ; Dickinson, J. ; Gill, A. ; Muller, P. ; Sekar, R. ; Reid, R. A. ; Unterschneider, J. ; Welsh, A. ; Marlow, J. ; Hyett, Jon ; Walker, S. ; Morris, J. ; Watson, D. ; McKinlay, C. ; Harris, S. ; Lim, K. I. ; Lalji, S. ; Magee, L. A. ; Lee, T. ; Li, J. ; Hutfield, A. ; Ansermino, M. ; Robinson, W. ; Singer, J. ; Synnes, A. R. ; Burrows, J. ; Audibert, F. ; Bujold, E. ; Piedboeuf, B. ; international STRIDER Consortium. / STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction) : An international consortium of randomised placebo-controlled trials. In: BMC Pregnancy and Childbirth. 2017 ; Vol. 17, No. 1.
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abstract = "Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis.",
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author = "A. Pels and Kenny, {L. C.} and Z. Alfirevic and Baker, {P. N.} and {von Dadelszen}, P. and C. Gluud and Kariya, {C. T.} and Mol, {B. W.} and A. Papageorghiou and {van Wassenaer-Leemhuis}, {A. G.} and W. Ganzevoort and Groom, {K. M.} and McCowan, {L. M.} and Stone, {P. R.} and A. Lee and L. Mackay and C. Oyston and G. Gardener and A. Khashan and J. Eustace and E. Dempsey and R. Jackson and J. Dickinson and A. Gill and P. Muller and R. Sekar and Reid, {R. A.} and J. Unterschneider and A. Welsh and J. Marlow and Jon Hyett and S. Walker and J. Morris and D. Watson and C. McKinlay and S. Harris and Lim, {K. I.} and S. Lalji and Magee, {L. A.} and T. Lee and J. Li and A. Hutfield and M. Ansermino and W. Robinson and J. Singer and Synnes, {A. R.} and J. Burrows and F. Audibert and E. Bujold and B. Piedboeuf and {international STRIDER Consortium}",
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Pels, A, Kenny, LC, Alfirevic, Z, Baker, PN, von Dadelszen, P, Gluud, C, Kariya, CT, Mol, BW, Papageorghiou, A, van Wassenaer-Leemhuis, AG, Ganzevoort, W, Groom, KM, McCowan, LM, Stone, PR, Lee, A, Mackay, L, Oyston, C, Gardener, G, Khashan, A, Eustace, J, Dempsey, E, Jackson, R, Dickinson, J, Gill, A, Muller, P, Sekar, R, Reid, RA, Unterschneider, J, Welsh, A, Marlow, J, Hyett, J, Walker, S, Morris, J, Watson, D, McKinlay, C, Harris, S, Lim, KI, Lalji, S, Magee, LA, Lee, T, Li, J, Hutfield, A, Ansermino, M, Robinson, W, Singer, J, Synnes, AR, Burrows, J, Audibert, F, Bujold, E, Piedboeuf, B & international STRIDER Consortium 2017, 'STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): An international consortium of randomised placebo-controlled trials', BMC Pregnancy and Childbirth, vol. 17, no. 1, 440. https://doi.org/10.1186/s12884-017-1594-z

STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction) : An international consortium of randomised placebo-controlled trials. / Pels, A.; Kenny, L. C.; Alfirevic, Z.; Baker, P. N.; von Dadelszen, P.; Gluud, C.; Kariya, C. T.; Mol, B. W.; Papageorghiou, A.; van Wassenaer-Leemhuis, A. G.; Ganzevoort, W.; Groom, K. M.; McCowan, L. M.; Stone, P. R.; Lee, A.; Mackay, L.; Oyston, C.; Gardener, G.; Khashan, A.; Eustace, J.; Dempsey, E.; Jackson, R.; Dickinson, J.; Gill, A.; Muller, P.; Sekar, R.; Reid, R. A.; Unterschneider, J.; Welsh, A.; Marlow, J.; Hyett, Jon; Walker, S.; Morris, J.; Watson, D.; McKinlay, C.; Harris, S.; Lim, K. I.; Lalji, S.; Magee, L. A.; Lee, T.; Li, J.; Hutfield, A.; Ansermino, M.; Robinson, W.; Singer, J.; Synnes, A. R.; Burrows, J.; Audibert, F.; Bujold, E.; Piedboeuf, B.; international STRIDER Consortium.

In: BMC Pregnancy and Childbirth, Vol. 17, No. 1, 440, 28.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction)

T2 - BMC Pregnancy and Childbirth

AU - Pels, A.

AU - Kenny, L. C.

AU - Alfirevic, Z.

AU - Baker, P. N.

AU - von Dadelszen, P.

AU - Gluud, C.

AU - Kariya, C. T.

AU - Mol, B. W.

AU - Papageorghiou, A.

AU - van Wassenaer-Leemhuis, A. G.

AU - Ganzevoort, W.

AU - Groom, K. M.

AU - McCowan, L. M.

AU - Stone, P. R.

AU - Lee, A.

AU - Mackay, L.

AU - Oyston, C.

AU - Gardener, G.

AU - Khashan, A.

AU - Eustace, J.

AU - Dempsey, E.

AU - Jackson, R.

AU - Dickinson, J.

AU - Gill, A.

AU - Muller, P.

AU - Sekar, R.

AU - Reid, R. A.

AU - Unterschneider, J.

AU - Welsh, A.

AU - Marlow, J.

AU - Hyett, Jon

AU - Walker, S.

AU - Morris, J.

AU - Watson, D.

AU - McKinlay, C.

AU - Harris, S.

AU - Lim, K. I.

AU - Lalji, S.

AU - Magee, L. A.

AU - Lee, T.

AU - Li, J.

AU - Hutfield, A.

AU - Ansermino, M.

AU - Robinson, W.

AU - Singer, J.

AU - Synnes, A. R.

AU - Burrows, J.

AU - Audibert, F.

AU - Bujold, E.

AU - Piedboeuf, B.

AU - international STRIDER Consortium

PY - 2017/12/28

Y1 - 2017/12/28

N2 - Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis.

AB - Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis.

KW - Fetal growth restriction

KW - Neonatal morbidity

KW - Neonatal mortality

KW - Placental insufficiency

KW - Randomised placebo controlled trial

KW - Sildenafil

UR - http://www.scopus.com/inward/record.url?scp=85039845763&partnerID=8YFLogxK

U2 - 10.1186/s12884-017-1594-z

DO - 10.1186/s12884-017-1594-z

M3 - Article

VL - 17

JO - BMC Pregnancy and Childbirth

JF - BMC Pregnancy and Childbirth

SN - 1471-2393

IS - 1

M1 - 440

ER -