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

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ClinicalTrials.gov Identifier: NCT02277132
Recruitment Status : Terminated (Results of interim analysis)
First Posted : October 28, 2014
Last Update Posted : July 25, 2018
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Wessel Ganzevoort, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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 Type : Interventional  (Clinical Trial)
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 : January 2015
Actual Primary Completion Date : July 19, 2018
Actual Study Completion Date : July 19, 2018

Resource links provided by the National Library of Medicine


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 Name: 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




Primary Outcome Measures :
  1. Intact neonatal survival until term age [ Time Frame: Term age, up to 20 weeks after randomization ]

Secondary Outcome Measures :
  1. Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At baseline ]
    If possible in designated clinic



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02277132


Locations
Netherlands
Radboud Medisch Centrum Nijmegen
Nijmegen, Gelderland, Netherlands, 6525GA
Maastricht Universitair Medisch Centrum
Maastricht, Limburg, Netherlands, 6202AZ
Maxima Medisch Centrum
Veldhoven, Noord Brabant, Netherlands, 5504 DB
Vrije Universiteit Medisch Centrum
Amsterdam, Noord Holland, Netherlands, 1081HV
Academisch Medisch Centrum
Amsterdam, Noord Holland, Netherlands, 1105AZ
Isala Klinieken
Zwolle, Overijssel, Netherlands, 8025 AB
Leids Universitair Medisch Centrum
Leiden, Zuid Holland, Netherlands, 2333ZA
Erasmus Medisch Centrum Rotterdam
Rotterdam, Zuid Holland, Netherlands, 3015CE
Universitair Medisch Centrum Groningen
Groningen, Netherlands, 9713GZ
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)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wessel Ganzevoort, J.W. Ganzevoort MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02277132     History of Changes
Other Study ID Numbers: 80-83600-98-20081
First Posted: October 28, 2014    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018

Keywords provided by Wessel Ganzevoort, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Fetal growth restriction
Sildenafil

Additional relevant MeSH terms:
Fetal Growth Retardation
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents