Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction

NCT ID: NCT02442492

Last Updated: 2020-02-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-04-30

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sildenafil

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

Group Type: ACTIVE_COMPARATOR

Sildenafil

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Sildenafil

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

Placebo

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

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Kenneth Lim

Study Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Kenneth Lim, MD FRCSC

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

Royal Alexandra Hospital

Edmonton, Alberta, Canada

BC Women's Hospital/University of British Columbia

Vancouver, British Columbia, Canada

London Health Sciences Centre

London, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

CHU de Quebec - Universite Laval

Québec, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 35799272 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29282009 (View on PubMed)

Other Identifiers

H15-00899

Identifier Type: -

Identifier Source: org_study_id