The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)

NCT ID: NCT02277132

Last Updated: 2018-07-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-07-19

Brief Summary

Rationale: Severe, early-onset fetal growth restriction (FGR) due to placental insufficiency is associated with a high risk of perinatal morbidity with long-lasting sequelae and mortality. Placental insufficiency is the result of abnormal formation and function of the placenta (placentation) with inadequate remodelling of the maternal spiral (uteroplacental) arteries. There is currently no therapy available with demonstrated effectiveness. Evidence suggests Sildenafil citrate improves uteroplacental blood flow, growth, and meaningful outcomes.

Objective: To evaluate the effectiveness of sildenafil (versus placebo) in achieving healthy perinatal survival.

Study design: Multicenter nationwide randomized placebo-controlled clinical trial.

Study population: Women with a singleton pregnancy between 20 and 30 weeks with severe fetal growth restriction of likely placental origin, and with estimated significant likelihood of perinatal death.

Intervention: Sildenafil 25mg or placebo tablet orally three times daily. Main study parameters/endpoints: Perinatal healthy survival, i.e. survival without severe neonatal morbidity at term age.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Taking tablets three times daily. No additional ultrasounds, other than standard clinical protocol, one extra blood sample at inclusion. No risks anticipated, unexpected medication-associated risks can't be excluded on beforehand.

Conditions

Fetal Growth Restriction

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

Group Type: ACTIVE_COMPARATOR

Sildenafil

Intervention Type: DRUG

Sildenafil 25 mg three times daily orally from randomization until delivery

Placebo

Placebo tablets three times daily orally from randomization until delivery

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets three times daily orally from randomization until delivery

Interventions

Sildenafil

Sildenafil 25 mg three times daily orally from randomization until delivery

Intervention Type: DRUG

Placebo

Placebo tablets three times daily orally from randomization until delivery

Intervention Type: DRUG

Other Intervention Names

Viagra

Eligibility Criteria

Inclusion Criteria

• At 20+0-27+6 weeks: an ultrasound measurement of the fetal abdominal circumference (AC) <3rd percentile for gestational age or an ultrasound estimate of fetal weight (EFW) <5th percentile OR
• At 28+0-29+6 weeks: an ultrasound estimate of fetal weight (EFW) <700 grams using Hadlock C formula AND
• Likely placental origin defined by (a AND/OR b AND/OR c AND/OR d)

• The presence of uterine artery notching
• Abnormal flow velocity patterns of the umbilical artery or middle cerebral artery
• Maternal hypertensive disorders
• Low PlGF in point-of-care assessment

Exclusion Criteria

• Plan to terminate pregnancy for maternal or fetal indication within days
• Known multiple pregnancy
• Identified congenital anomalies or congenital infection
• Maternal age at eligibility <18 years
• Cocaine use
• Current use of sildenafil
• Current use of cyp3A5 inhibitors: amiodaron, azitromycine, ciclosporine, claritromycine, diltiazem, erytromycine, fluconazol, itraconazol, ketoconazol, verapamil, voriconazol.
• Recent myocardial infarction or stroke

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Wessel Ganzevoort

J.W. Ganzevoort MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J.W. Ganzevoort, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

K Bloemenkamp, MD PhD

Role: STUDY_CHAIR

Leiden University Medical Center

P von Dadelszen, Prof

Role: STUDY_CHAIR

University of British Columbia

C de Groot, Prof

Role: STUDY_CHAIR

VU Medisch Centrum

M.W. de Laat, MD PhD

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

B.W. Mol, Prof

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

M. Porath, MD PhD

Role: STUDY_CHAIR

Perinataal Centrum MMC Veldhoven

J.A.M. van der Post, Prof

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

A. van Wassenaer, MD PhD

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

Radboud Medisch Centrum Nijmegen

Nijmegen, Gelderland, Netherlands

Maastricht Universitair Medisch Centrum

Maastricht, Limburg, Netherlands

Maxima Medisch Centrum

Veldhoven, North Brabant, Netherlands

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, Netherlands

Academisch Medisch Centrum

Amsterdam, North Holland, Netherlands

Isala Klinieken

Zwolle, Overijssel, Netherlands

Leids Universitair Medisch Centrum

Leiden, South Holland, Netherlands

Erasmus Medisch Centrum Rotterdam

Rotterdam, South Holland, Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Countries

Netherlands

References

Pels A, Derks J, Elvan-Taspinar A, van Drongelen J, de Boer M, Duvekot H, van Laar J, van Eyck J, Al-Nasiry S, Sueters M, Post M, Onland W, van Wassenaer-Leemhuis A, Naaktgeboren C, Jakobsen JC, Gluud C, Duijnhoven RG, Lely T, Gordijn S, Ganzevoort W; Dutch STRIDER Trial Group. Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e205323. doi: 10.1001/jamanetworkopen.2020.5323.

Reference Type: DERIVED

PMID: 32585017 (View on PubMed)

Pels A, Jakobsen JC, Ganzevoort W, Naaktgeboren CA, Onland W, van Wassenaer-Leemhuis AG, Gluud C. 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 restriction. Trials. 2019 Jan 11;20(1):42. doi: 10.1186/s13063-018-3136-z.

Reference Type: DERIVED

PMID: 30635020 (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

80-83600-98-20081

Identifier Type: -

Identifier Source: org_study_id