NCT02442492

Brief Summary

Early-onset placental intrauterine growth restriction (EO IUGR) is associated with a high risk of perinatal morbidity and mortality. In association with reduced circulating placental growth factor (PlGF) EO IUGR results from abnormal placentation with inadequate remodelling of the maternal uteroplacental arteries. There is no known treatment for placental IUGR. Management involves intensive fetal surveillance with delivery with evidence of serious fetal compromise. However, remote from term, delivery is associated with significant perinatal mortality and morbidity. Sildenafil vasodilates the uteroplacental vessels of IUGR-affected pregnancies and may represent a novel therapy.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2017

Geographic Reach
1 country

5 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 5, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 13, 2015

Completed
1.6 years until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2018

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2019

Completed
Last Updated

February 11, 2020

Status Verified

February 1, 2020

Enrollment Period

1.5 years

First QC Date

May 5, 2015

Last Update Submit

February 7, 2020

Conditions

Intrauterine Growth Restriction (IUGR)Fetal Growth Restriction (FGR)

Keywords

sildenafilIUGRFGRSTRIDER

Outcome Measures

Primary Outcomes (1)

  • compare the gestational age at delivery (d) between sildenafil- and placebo-treated groups

    6 weeks after postpartum

Secondary Outcomes (4)

  • live birth

    at delivery if alive

  • survival to hospital discharge

    measured at the final hospital discharge (average upto 6 weeks postpartum)

  • intact survival (defined as survival to estimated due date (EDD) without evidence of severe central nervous system [CNS] injury [by ultrasound and/or magnetic resonance imaging (MRI)])

    measured at estimated due date (EDD)

  • composite non-CNS (Central Nervous System) severe morbidity (one/more of bronchopulmonary dysplasia requiring supplemental oxygen on hospital discharge, ≥grade 3 retinopathy of prematurity, or necrotising enterocolitis)

    up to 6 weeks after postpartum or final discharge which ever is sooner

Other Outcomes (10)

  • Maternal - symptomatic hypotension

    up to 6 weeks after postpartum or final discharge which ever is sooner

  • Maternal - pre-eclampsia

    from randomisation to delivery (expected to be assessed weekly)

  • Maternal - mode of delivery

    At delivery

  • +7 more other outcomes

Study Arms (2)

Sildenafil

ACTIVE COMPARATOR

Sildenafil 25 mg tablets three times daily orally from randomization until delivery or 31+6 weeks of gestational age, whichever is sooner.

Drug: Sildenafil

Placebo

PLACEBO COMPARATOR

Placebo 25 mg tablets three times daily orally from randomization until delivery or 31+6 weeks of gestational age, whichever is sooner.

Drug: Placebo

Interventions

SildenafilDRUG

Sildenafil 25 mg tablets three times daily orally from randomization until delivery or 31+6 weeks of gestational age, whichever is sooner.

Sildenafil
PlaceboDRUG

Placebo 25 mg tablets three times daily orally from randomization until delivery or 31+6 weeks of gestational age, whichever is sooner.

Placebo

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Gestational age from 18+0 - 27+6 weeks
  • AND
  • EO IUGR, defined as
  • ultrasound (U/S) measurement of the fetal abdominal circumference (AC) \<10th percentile for gestational age and/or documented reduced fetal growth velocity complicating either a prior EO IUGR with adverse perinatal outcome or abnormal uterine artery waveform in the index pregnancy;
  • U/S estimate of fetal weight (EFW) \<700g
  • AND
  • Serum PlGF \< 5th percentile for gestational age

You may not qualify if:

  • known fetal aneuploidy
  • known fetal anomaly/syndrome/congenital infection confirmed at the time of enrolment
  • decision made to terminate pregnancy
  • current cocaine or vasoconstrictor use (e.g. crystal meth) (risk of acute cardiac events)
  • contraindication to sildenafil therapy, e.g. known significant maternal cardiac disease, left ventricular outflow tract obstruction, concomitant treatment with nitrates or previous allergy to sildenafil
  • known HIV positive status (due drug-drug interaction between sildenafil and antiretrovirals)
  • receiving peripheral alpha-blockers (e.g. prazosin)
  • prior participation in a STRIDER trials
  • pre-eclampsia or gestational hypertension diagnosed

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

BC Women's Hospital/University of British Columbia

Vancouver, British Columbia, V7H3N1, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

CHU de Quebec - Universite Laval

Québec, Quebec, G2N 0B2, Canada

Location

Related Publications (2)

  • von Dadelszen P, Audibert F, Bujold E, Bone JN, Sandhu A, Li J, Kariya C, Chung Y, Lee T, Au K, Skoll MA, Vidler M, Magee LA, Piedboeuf B, Baker PN, Lalji S, Lim KI. Halting the Canadian STRIDER randomised controlled trial of sildenafil for severe, early-onset fetal growth restriction: ethical, methodological, and pragmatic considerations. BMC Res Notes. 2022 Jul 7;15(1):244. doi: 10.1186/s13104-022-06107-y.

    PMID: 35799272DERIVED

  • Pels A, Kenny LC, Alfirevic Z, Baker PN, von Dadelszen P, Gluud C, Kariya CT, Mol BW, Papageorghiou AT, van Wassenaer-Leemhuis AG, Ganzevoort W, Groom KM; international STRIDER Consortium. STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): an international consortium of randomised placebo-controlled trials. BMC Pregnancy Childbirth. 2017 Dec 28;17(1):440. doi: 10.1186/s12884-017-1594-z.

    PMID: 29282009DERIVED

MeSH Terms

Conditions

Fetal Growth Retardation

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Fetal DiseasesPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGrowth DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Peter von Dadelszen, BMedSc, MBChB, DipObst, DPhil,

    University of British Columbia

    PRINCIPAL INVESTIGATOR

  • Kenneth Lim, MD FRCSC

    University of British Columbia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Study Principal Investigator

Study Record Dates

First Submitted

May 5, 2015

First Posted

May 13, 2015

Study Start

January 1, 2017

Primary Completion

July 1, 2018

Study Completion

April 1, 2019

Last Updated

February 11, 2020

Record last verified: 2020-02

Locations

CA(5)