Detailed Statistical Analysis Plan for the Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction) Randomised Clinical Trial on Sildenafil Versus Placebo for Pregnant Women with Severe Early Onset Fetal Growth...

Overview

Journal Trials

Publisher Biomed Central

Specialties General Medicine
Pharmacology

Date 2019 Jan 13

PMID 30635020

Citations 4

Authors

Anouk Pels

Janus C Jakobsen

Wessel Ganzevoort

Christiana A Naaktgeboren

Wes Onland

Aleid G van Wassenaer-Leemhuis

Christian Gluud

Affiliations

Soon will be listed here.

Abstract

Objective: The objective of the Dutch Sildenafil therapy in dismal prognosis early onset fetal growth restriction (STRIDER) randomised clinical trial is to assess the beneficial and harmful effects of sildenafil versus placebo on fetal and neonatal mortality in pregnant women with severe early-onset fetal growth restriction. The objective of this detailed statistical analysis plan is to minimize the risks of selective reporting and data-driven analysis.

Setting: The setting is 10 tertiary care hospitals and one secondary care hospital in The Netherlands.

Participants: The participants will be 360 pregnant women with severe early-onset fetal growth restriction.

Interventions: The intervention is sildenafil 25 mg or placebo orally three times a day.

Primary And Secondary Outcome Measures: The primary outcome is a composite of death or major neonatal morbidity assessed at hospital discharge. The secondary outcomes are neurodevelopmental impairment; mean scores of the Bayley III cognitive and motor assessment; the proportion of patients experiencing either preeclampsia or haemolysis, elevated liver enzymes, and low platelets syndrome; pulsatility index of uterine arteries, umbilical artery, and middle cerebral artery; birthweight; and gestational age at either delivery or intra-uterine death.

Results: A detailed statistical analysis is presented, including pre-defined exploratory outcomes and planned subgroup analyses. One interim analysis after 180 patients had completed the study was planned and a strategy to minimise the risks of type I errors due to repetitive testing is presented. During review of this manuscript the interim analysis was performed by the Data Safety Monitoring Board and early stopping of the trial was recommended. Final analyses will be conducted independently by two statistically qualified persons following the present plan.

Conclusion: This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data and updated after stopping of the trial at interim analysis.

Trial Registration: ClinicalTrials.gov, NCT02277132 . Registered on 29 September 2014. Original protocol for the study: doi: https://doi.org/10.5281/zenodo.56148.

Citing Articles

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Ssengonzi R, Wang Y, Maeda-Smithies N, Li F J Pregnancy Child Health. 2024; 6.

PMID: 38476467 PMC: 10929736. DOI: 10.29011/jpch-121.100021.

Interventions affecting the nitric oxide pathway versus placebo or no therapy for fetal growth restriction in pregnancy.

Pels A, Ganzevoort W, Kenny L, Baker P, von Dadelszen P, Gluud C Cochrane Database Syst Rev. 2023; 7:CD014498.

PMID: 37428872 PMC: 10332237. DOI: 10.1002/14651858.CD014498.

Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction: A Randomized Clinical Trial.

Pels A, Derks J, Elvan-Taspinar A, van Drongelen J, de Boer M, Duvekot H JAMA Netw Open. 2020; 3(6):e205323.

PMID: 32585017 PMC: 7301225. DOI: 10.1001/jamanetworkopen.2020.5323.

Low Birth Weight, Blood Pressure and Renal Susceptibility.

Coats L, Davis G, Newsome A, Ojeda N, Alexander B Curr Hypertens Rep. 2019; 21(8):62.

PMID: 31228030 PMC: 8109258. DOI: 10.1007/s11906-019-0969-0.

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