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

Fetal Growth Restriction Clinical Trial

— STRIDER  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02277132
• Other study ID #: 80-83600-98-20081
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: January 2015
• Est. completion date: July 19, 2018

Study information

• Verified date: July 2018
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 216
• Est. completion date: July 19, 2018
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

Inclusion criteria ((I OR II) AND III):

• 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

Related Conditions & MeSH terms

• Fetal Growth Restriction
• Fetal Growth Retardation

Intervention

Drug:
• Sildenafil
Sildenafil 25 mg three times daily orally from randomization until delivery
• Placebo
Placebo tablets three times daily orally from randomization until delivery

Locations

Country	Name	City	State
Netherlands	Academisch Medisch Centrum	Amsterdam	Noord Holland
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam	Noord Holland
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Leids Universitair Medisch Centrum	Leiden	Zuid Holland
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht	Limburg
Netherlands	Radboud Medisch Centrum Nijmegen	Nijmegen	Gelderland
Netherlands	Erasmus Medisch Centrum Rotterdam	Rotterdam	Zuid Holland
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Netherlands	Maxima Medisch Centrum	Veldhoven	Noord Brabant
Netherlands	Isala Klinieken	Zwolle	Overijssel

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fetal ultrasound and Doppler studies: estimated fetal weight, abdominal circumference and Doppler of umbilical artery	Umbilical artery, middle cerebral artery, ductus venosus and aortic isthmus Doppler indices; fetal biometry; amniotic fluid index; deepest vertical amniotic fluid pocket.	At contact moments with the patients, up to 20 weeks after randomization
Other	PlGF (Placental Growth Factor) point-of-care assessment	If possible in designated clinic	At baseline
Primary	Intact neonatal survival until term age		Term age, up to 20 weeks after randomization
Secondary	Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC)	Average daily increase in ultrasound-estimated AC	At contact moments with the patient, up to 20 weeks after randomization
Secondary	Age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score)		2 years corrected age, up to 2 years and three months after randomization
Secondary	Co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome (Hemolysis Elevated Liver enzymes Low Platelets)		At contact moments with the patient, up to 20 weeks after randomization