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Randomized Controlled Trial
. 2017 Dec 28;17(1):440.
doi: 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

A Pels  1 , L C Kenny  2 , Z Alfirevic  3 , P N Baker  4 , Peter von Dadelszen  5 , C Gluud  6 , C T Kariya  5 , B W Mol  7 , A T Papageorghiou  8 , A G van Wassenaer-Leemhuis  9 , W Ganzevoort  9 , K M Groom  10 ; international STRIDER Consortium
Affiliations
Randomized Controlled Trial

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

A Pels et al. BMC Pregnancy Childbirth. .

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.

Trial registrations: New Zealand and Australia: ACTRN12612000584831 . Registered 30/05/2012. Canada: NCT02442492 . Registered 05/05/2015. Ireland: CT 900/572/1 . Registered 15/07/2015. The Netherlands: NCT02277132 . Registered 29/09/2014. United Kingdom: ISRCTN39133303 . Registered 31/07/2014.

Keywords: Fetal growth restriction; Neonatal morbidity; Neonatal mortality; Placental insufficiency; Randomised placebo controlled trial; Sildenafil.

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Conflict of interest statement

Ethics approval and consent to participate

New Zealand/Australia: New Zealand Health and Disability Ethics Committee (CEN/12/06/028/AM05), Royal Brisbane & Women’s Hospital Human Research Ethics Committee (HREC/14/ORBW/178), and King Edward Memorial Hospital Ethics Committee (2014071EW).

Canada: University of British Columbia/Children’s and Women’s Health Centre of BC Research Ethics Board (H15–00899).

Ireland: provisional approval by Cork University Teaching Hospital Ethics Committee (ECM 5 (9) 02/02/16), full approval will be granted on confirmation of sponsorship (pending).

The Netherlands: MET AMC (NL41894.018.14).

The United Kingdom: 14.NE.0011.

All participating women are provided with written and verbal information regarding the trial they are going to enter and provide signed informed consent in advance of participation. Any protocol modifications once the trials are underway will be reviewed by the local Ethics Committee. Appropriate clinical trial insurance is in place for participants of each trial in the event that any participant experiences harm as a consequence of participation in these trials.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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