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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02277132
Other study ID # 80-83600-98-20081
Secondary ID
Status Terminated
Phase Phase 2/Phase 3
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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