Fetal Growth RestrictionPhase 2/3STRIDERNCT02277132
The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
A Phase 2/3 study testing Sildenafil in people with Fetal Growth Restriction, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 10 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Fetal Growth Restriction
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 216 participants
- Where
- 10 sitesNetherlands
- Study dates
- Jan 2015to 19 Jul 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Netherlands10 sites
Vrije Universiteit Medisch Centrum
Amsterdam, North Holland, 1081HV
Academisch Medisch Centrum
Amsterdam, North Holland, 1105AZ
Universitair Medisch Centrum Groningen
Groningen, Provincie Groningen, 9713GZ
Leids Universitair Medisch Centrum
Leiden, South Holland, 2333ZA
Maastricht Universitair Medisch Centrum
Maastricht, Limburg, 6202AZ
Radboud Medisch Centrum Nijmegen
Nijmegen, Gelderland, 6525GA
Erasmus Medisch Centrum Rotterdam
Rotterdam, South Holland, 3015CE
Universitair Medisch Centrum Utrecht
Utrecht, Utrecht, 3584CX
Maxima Medisch Centrum
Veldhoven, North Brabant, 5504 DB
Isala Klinieken
Zwolle, Overijssel, 8025 AB
About this study
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.
Read more
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
- Being tested
- Sildenafil, Placebo
- Keywords
- Fetal growth restriction, Sildenafil
- Medical subject headings
- Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Viagra
Sildenafil 25 mg three times daily orally from randomization until delivery
PlaceboDrug
Placebo tablets three times daily orally from randomization until delivery
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Active comparator | Sildenafil 25 mg tablets three times daily orally from randomization until delivery Receives: Drug: Sildenafil |
| Placebo | Placebo comparator | Placebo tablets three times daily orally from randomization until delivery Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intact neonatal survival until term age
Measured: Term age, up to 20 weeks after randomization
Secondary outcomes (3)
Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC)
Average daily increase in ultrasound-estimated AC
Measured: At contact moments with the patient, up to 20 weeks after randomization
Age-adequate performance on the two-year Bayley scales of infant development (BSID)-III (composite cognitive score and composite motor score)
Measured: 2 years corrected age, up to 2 years and three months after randomization
Co-incidence and severity of the maternal syndrome of pre-eclampsia / HELLP-syndrome (Hemolysis Elevated Liver enzymes Low Platelets)
Measured: At contact moments with the patient, up to 20 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startJan 2015
- Primary completion19 Jul 2018
- Study completion19 Jul 2018
Why it stopped: Results of interim analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Fetal Growth RestrictionStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 216 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, Wessel Ganzevoort, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- J.W. Ganzevoort, MD PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)K Bloemenkamp, MD PhD, Study chair, Leiden University Medical CenterP von Dadelszen, Prof, Study chair, University of British ColumbiaC de Groot, Prof, Study chair, VU Medisch CentrumM.W. de Laat, MD PhD, Study chair, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)B.W. Mol, Prof, Study chair, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)M. Porath, MD PhD, Study chair, Perinataal Centrum MMC VeldhovenJ.A.M. van der Post, Prof, Study chair, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02277132
- Sponsor's protocol ID
- 80-83600-98-20081
- Acronym
- STRIDER
- Status last verified
- Jul 2018
- First submitted
- 29 Sep 2014
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32585017Pels 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.
PubMed 30635020Pels 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.
PubMed 29282009
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
- ClinicalTrials.gov ID
- NCT02277132
- Acronym / sponsor ID
- STRIDER / 80-83600-98-20081
- Conditions
- Fetal Growth Restriction
- Keywords
- Fetal growth restriction, Sildenafil
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Results of interim analysis
- Enrolment
- 216 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Jan 2015
- Primary completion
- 19 Jul 2018 (actual)
- Study completion
- 19 Jul 2018 (actual)
- First posted
- 28 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Active comparator | Drug: SildenafilSildenafil 25 mg tablets three times daily orally from randomization until delivery |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablets three times daily orally from randomization until delivery |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilAlso: ViagraSildenafil 25 mg three times daily orally from randomization until delivery | Drug | Sildenafil |
| PlaceboPlacebo tablets three times daily orally from randomization until delivery | Drug | Placebo |
Primary outcome
Intact neonatal survival until term age
Time frame: Term age, up to 20 weeks after randomization
3 secondary outcomes
Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC)
Time frame: At contact moments with the patient, up to 20 weeks after randomization
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
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
Results and safety
The study was stopped early (reason given: Results of interim analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Derived from this study: PubMed 32585017Pels 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.
- Derived from this study: PubMed 30635020Pels 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.
- Derived from this study: PubMed 29282009Pels 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J.W. Ganzevoort, MD PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
K Bloemenkamp, MD PhD study chair
Leiden University Medical Center
P von Dadelszen, Prof study chair
University of British Columbia
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sildenafil in people with Fetal Growth Restriction, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 10 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Results of interim analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intact neonatal survival until term age (time frame: Term age, up to 20 weeks after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02277132, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.