The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 216
- 试验地点
- 10
- 主要终点
- Intact neonatal survival until term age
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Sildenafil
Sildenafil 25 mg tablets three times daily orally from randomization until delivery
干预措施: Sildenafil (Drug)
Placebo
Placebo tablets three times daily orally from randomization until delivery
干预措施: Placebo (Drug)
结局指标
主要结局
Intact neonatal survival until term age
时间窗: Term age, up to 20 weeks after randomization
次要结局
- 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)
- Fetal growth velocity assessed by ultrasound: abdominal circumference measurements (AC)(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)(2 years corrected age, up to 2 years and three months after randomization)
研究者
Wessel Ganzevoort
J.W. Ganzevoort MD PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)