The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction) (STRIDER)
Primary Purpose
Fetal Growth Restriction
Status
Terminated
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Sildenafil
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fetal Growth Restriction focused on measuring Fetal growth restriction, Sildenafil
Eligibility 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
Sites / Locations
- Radboud Medisch Centrum Nijmegen
- Maastricht Universitair Medisch Centrum
- Maxima Medisch Centrum
- Vrije Universiteit Medisch Centrum
- Academisch Medisch Centrum
- Isala Klinieken
- Leids Universitair Medisch Centrum
- Erasmus Medisch Centrum Rotterdam
- Universitair Medisch Centrum Groningen
- Universitair Medisch Centrum Utrecht
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Sildenafil
Placebo
Arm Description
Sildenafil 25 mg tablets three times daily orally from randomization until delivery
Placebo tablets three times daily orally from randomization until delivery
Outcomes
Primary Outcome Measures
Intact neonatal survival until term age
Secondary Outcome Measures
Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC)
Average daily increase in ultrasound-estimated AC
Age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score)
Co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome (Hemolysis Elevated Liver enzymes Low Platelets)
Full Information
NCT ID
NCT02277132
First Posted
September 29, 2014
Last Updated
July 24, 2018
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT02277132
Brief Title
The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
Acronym
STRIDER
Official Title
The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
Results of interim analysis
Study Start Date
January 2015 (undefined)
Primary Completion Date
July 19, 2018 (Actual)
Study Completion Date
July 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fetal Growth Restriction
Keywords
Fetal growth restriction, Sildenafil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
216 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sildenafil
Arm Type
Active Comparator
Arm Description
Sildenafil 25 mg tablets three times daily orally from randomization until delivery
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablets three times daily orally from randomization until delivery
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Other Intervention Name(s)
Viagra
Intervention Description
Sildenafil 25 mg three times daily orally from randomization until delivery
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets three times daily orally from randomization until delivery
Primary Outcome Measure Information:
Title
Intact neonatal survival until term age
Time Frame
Term age, up to 20 weeks after randomization
Secondary Outcome Measure Information:
Title
Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC)
Description
Average daily increase in ultrasound-estimated AC
Time Frame
At contact moments with the patient, up to 20 weeks after randomization
Title
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
Title
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 Pre-specified Outcome Measures:
Title
Fetal ultrasound and Doppler studies: estimated fetal weight, abdominal circumference and Doppler of umbilical artery
Description
Umbilical artery, middle cerebral artery, ductus venosus and aortic isthmus Doppler indices; fetal biometry; amniotic fluid index; deepest vertical amniotic fluid pocket.
Time Frame
At contact moments with the patients, up to 20 weeks after randomization
Title
PlGF (Placental Growth Factor) point-of-care assessment
Description
If possible in designated clinic
Time Frame
At baseline
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J.W. Ganzevoort, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
K Bloemenkamp, MD PhD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
P von Dadelszen, Prof
Organizational Affiliation
University of British Columbia
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
C de Groot, Prof
Organizational Affiliation
VU Medisch Centrum
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
M.W. de Laat, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
B.W. Mol, Prof
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
M. Porath, MD PhD
Organizational Affiliation
Perinataal Centrum MMC Veldhoven
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
J.A.M. van der Post, Prof
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
A. van Wassenaer, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Study Chair
Facility Information:
Facility Name
Radboud Medisch Centrum Nijmegen
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6525GA
Country
Netherlands
Facility Name
Maastricht Universitair Medisch Centrum
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6202AZ
Country
Netherlands
Facility Name
Maxima Medisch Centrum
City
Veldhoven
State/Province
Noord Brabant
ZIP/Postal Code
5504 DB
Country
Netherlands
Facility Name
Vrije Universiteit Medisch Centrum
City
Amsterdam
State/Province
Noord Holland
ZIP/Postal Code
1081HV
Country
Netherlands
Facility Name
Academisch Medisch Centrum
City
Amsterdam
State/Province
Noord Holland
ZIP/Postal Code
1105AZ
Country
Netherlands
Facility Name
Isala Klinieken
City
Zwolle
State/Province
Overijssel
ZIP/Postal Code
8025 AB
Country
Netherlands
Facility Name
Leids Universitair Medisch Centrum
City
Leiden
State/Province
Zuid Holland
ZIP/Postal Code
2333ZA
Country
Netherlands
Facility Name
Erasmus Medisch Centrum Rotterdam
City
Rotterdam
State/Province
Zuid Holland
ZIP/Postal Code
3015CE
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713GZ
Country
Netherlands
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
32585017
Citation
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.
Results Reference
derived
PubMed Identifier
30635020
Citation
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.
Results Reference
derived
PubMed Identifier
29282009
Citation
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.
Results Reference
derived
Learn more about this trial
The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
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