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

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02277132
• Collaborator: ZonMw: The Netherlands Organisation for Health Research and Development (Other)
• Enrollment: 216
• Locations: 10
• Arms: 2
• Duration (Months): 42.5
• Patients Per Site: 21.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fetal Growth Restriction	Drug: Sildenafil; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jul 19, 2018
• Actual Study Completion Date: Jul 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sildenafil Sildenafil 25 mg tablets three times daily orally from randomization until delivery	Drug: Sildenafil; Sildenafil 25 mg three times daily orally from randomization until delivery; Other Names: Viagra
Placebo Comparator: Placebo Placebo tablets three times daily orally from randomization until delivery	Drug: Placebo; Placebo tablets three times daily orally from randomization until delivery

Outcome Measures

Primary Outcome Measures

1. Intact neonatal survival until term age [Term age, up to 20 weeks after randomization]

Secondary Outcome Measures

1. Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC) [At contact moments with the patient, up to 20 weeks after randomization]

   Average daily increase in ultrasound-estimated AC

2. 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]

3. 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]

Other Outcome Measures

1. Fetal ultrasound and Doppler studies: estimated fetal weight, abdominal circumference and Doppler of umbilical artery [At contact moments with the patients, up to 20 weeks after randomization]

   Umbilical artery, middle cerebral artery, ductus venosus and aortic isthmus Doppler indices; fetal biometry; amniotic fluid index; deepest vertical amniotic fluid pocket.

2. PlGF (Placental Growth Factor) point-of-care assessment [At baseline]

   If possible in designated clinic

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud Medisch Centrum Nijmegen	Nijmegen	Gelderland	Netherlands	6525GA
2	Maastricht Universitair Medisch Centrum	Maastricht	Limburg	Netherlands	6202AZ
3	Maxima Medisch Centrum	Veldhoven	Noord Brabant	Netherlands	5504 DB
4	Vrije Universiteit Medisch Centrum	Amsterdam	Noord Holland	Netherlands	1081HV
5	Academisch Medisch Centrum	Amsterdam	Noord Holland	Netherlands	1105AZ
6	Isala Klinieken	Zwolle	Overijssel	Netherlands	8025 AB
7	Leids Universitair Medisch Centrum	Leiden	Zuid Holland	Netherlands	2333ZA
8	Erasmus Medisch Centrum Rotterdam	Rotterdam	Zuid Holland	Netherlands	3015CE
9	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713GZ
10	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584CX

Sponsors and Collaborators

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

Investigators

• Principal Investigator: J.W. Ganzevoort, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Study Chair: K Bloemenkamp, MD PhD, Leiden University Medical Center
• Study Chair: P von Dadelszen, Prof, University of British Columbia
• Study Chair: C de Groot, Prof, VU Medisch Centrum
• Study Chair: M.W. de Laat, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Study Chair: B.W. Mol, Prof, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Study Chair: M. Porath, MD PhD, Perinataal Centrum MMC Veldhoven
• Study Chair: J.A.M. van der Post, Prof, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Study Chair: A. van Wassenaer, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wessel Ganzevoort, J.W. Ganzevoort MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• ClinicalTrials.gov Identifier: NCT02277132
• Other Study ID Numbers: 80-83600-98-20081
• First Posted: Oct 28, 2014
• Last Update Posted: Jul 26, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Wessel Ganzevoort, J.W. Ganzevoort MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): Fetal growth restriction; Sildenafil
• Additional relevant MeSH terms: Fetal Growth Retardation; Sildenafil Citrate

Study Results

No Results Posted as of Jul 26, 2018