Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction

Fetal Growth Restriction (FGR) Clinical Trial

— STRIDERCan  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02442492
• Other study ID #: H15-00899
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: January 2017
• Est. completion date: April 2019

Study information

• Verified date: February 2020
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: April 2019
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	CHU de Quebec - Universite Laval	Quebec City	Quebec
Canada	BC Women's Hospital/University of British Columbia	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maternal - symptomatic hypotension		up to 6 weeks after postpartum or final discharge which ever is sooner
Other	Maternal - pre-eclampsia		from randomisation to delivery (expected to be assessed weekly)
Other	Maternal - mode of delivery		At delivery
Other	Maternal - haemorrhage requiring transfusion		At delivery
Other	Maternal - maternal plasma PlGF.		from randomisation to delivery (expected to be assessed weekly)
Other	Maternal - uterine artery Doppler indices		from randomisation to delivery (expected to be done weekly)
Other	Perinatal - fetal growth velocity		from randomisation to delivery (expected to be done weekly)
Other	Perinatal - fetal Doppler		from randomisation to delivery (expected to be done weekly)
Other	Perinatal - amniotic fluid		At randomisation, if done
Other	Perinatal - fetal heart indices		rom randomisation to delivery (expected to be done weekly)
Primary	compare the gestational age at delivery (d) between sildenafil- and placebo-treated groups		6 weeks after postpartum
Secondary	live birth		at delivery if alive
Secondary	survival to hospital discharge		measured at the final hospital discharge (average upto 6 weeks postpartum)
Secondary	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)
Secondary	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