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Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction (STRIDERCan)

Primary Purpose

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

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Sildenafil

Placebo

About this trial

This is an interventional treatment trial for Intrauterine Growth Restriction (IUGR) focused on measuring sildenafil, IUGR, FGR, STRIDER

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Gestational age from 18+0 - 27+6 weeks

AND

EO IUGR, defined as
1. 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;
  OR
2. U/S estimate of fetal weight (EFW) <700g

AND

Serum PlGF < 5th percentile for gestational age

Exclusion Criteria:

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

Sites / Locations

Royal Alexandra Hospital
BC Women's Hospital/University of British Columbia
London Health Sciences Centre
CHU Sainte-Justine
CHU de Quebec - Universite Laval

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sildenafil

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

live birth

survival to hospital discharge

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)])

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)

Full Information

NCT ID

NCT02442492

First Posted

May 5, 2015

Last Updated

February 7, 2020

Sponsor

University of British Columbia

1. Study Identification

Unique Protocol Identification Number

NCT02442492

Brief Title

Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction

Acronym

STRIDERCan

Official Title

STRIDER Canada: A Randomized Controlled Trial of Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction (Canada)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Terminated

Why Stopped

Trial terminated following Dutch DSMB recommendation for their Study

Study Start Date

January 2017 (Actual)

Primary Completion Date

July 2018 (Actual)

Study Completion Date

April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of British Columbia

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

STRIDER Canada is one of a consortium of STRIDER randomised controlled trials (RCTs) each of which is designed to determine whether or not maternal treatment with oral sildenafil citrate improves perinatal outcomes in pregnancies complicated by EO IUGR without increasing risks to the mother. STRIDER Canada is designed as investigator-initiated double-blind, randomised placebo-controlled trial of 90 women with a diagnosis of early-onset intrauterine growth restriction with an intention-to-treat analysis. 90 Women with affected pregnancies will be recruited and randomised to receive either sildenafil or placebo. Women reviewed in the participating fetal medicine with a diagnosis of a pregnancy affected by early-onset IUGR between 18+0 and 27+6 weeks of gestation and serum PlGF levels less than 5th percentile for gestational age will be considered for randomisation. In Canadian STRIDER, the treatment with either sildenafil or placebo (25 mg 3 times per day) will be applied from the time of randomisation until delivery, or up to 31+6 weeks of gestation whichever comes first. All patients randomly assigned to one of the treatments will be analysed together, regardless of whether or not they completed or received that treatment, on an intention to treat basis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

sildenafil, IUGR, FGR, STRIDER

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sildenafil

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sildenafil

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

6 weeks after postpartum

Secondary Outcome Measure Information:

Title

live birth

Time Frame

at delivery if alive

Title

survival to hospital discharge

Time Frame

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

Title

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)])

Time Frame

measured at estimated due date (EDD)

Title

Time Frame

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

Other Pre-specified Outcome Measures:

Title

Maternal - symptomatic hypotension

Time Frame

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

Title

Maternal - pre-eclampsia

Time Frame

from randomisation to delivery (expected to be assessed weekly)

Title

Maternal - mode of delivery

Time Frame

At delivery

Title

Maternal - haemorrhage requiring transfusion

Time Frame

At delivery

Title

Maternal - maternal plasma PlGF.

Time Frame

from randomisation to delivery (expected to be assessed weekly)

Title

Maternal - uterine artery Doppler indices

Time Frame

from randomisation to delivery (expected to be done weekly)

Title

Perinatal - fetal growth velocity

Time Frame

from randomisation to delivery (expected to be done weekly)

Title

Perinatal - fetal Doppler

Time Frame

from randomisation to delivery (expected to be done weekly)

Title

Perinatal - amniotic fluid

Time Frame

At randomisation, if done

Title

Perinatal - fetal heart indices

Time Frame

rom randomisation to delivery (expected to be done weekly)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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; OR U/S estimate of fetal weight (EFW) <700g AND Serum PlGF < 5th percentile for gestational age Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

University of British Columbia

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Kenneth Lim, MD FRCSC

Organizational Affiliation

University of British Columbia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Alexandra Hospital

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T5H 3V9

Country

Canada

Facility Name

BC Women's Hospital/University of British Columbia

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V7H3N1

Country

Canada

Facility Name

London Health Sciences Centre

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5W9

Country

Canada

Facility Name

CHU Sainte-Justine

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H3T 1C5

Country

Canada

Facility Name

CHU de Quebec - Universite Laval

City

Quebec City

State/Province

Quebec

ZIP/Postal Code

G2N 0B2

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

35799272

Citation

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.

Results Reference

derived

PubMed Identifier

29282009

Citation

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.

Results Reference

derived

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Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction

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