Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy, a Multicenter Prospective Randomized Double-blind Placebo-controlled Trial.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 33
- 主要终点
- Composite morbidity-mortality criterion including preeclampsia, intra-uterine growth retardation <10th percentile, placental abruption, Preterm birth < 37 weeks of gestation, Perinatal death, Maternal death
研究概览
简要总结
A randomized clinical trial to assess the efficiency of acetylsalicylic acid (aspirin) 150 mg/day started before 20 weeks of gestation in the prevention on maternal and fœtal complications in pregnant women with chronic hypertension.
详细描述
Chronic hypertension affects 1 to 5% of women of childbearing age. According to the literature, about 45% of pregnant women with chronic hypertension will develop complications such as superimposed preeclampsia (PE), placental abruption, Intra Uterine Growth Restriction (IUGR), perinatal death, maternal death, or preterm delivery. To date, there is no curative treatment of vascular complications of chronic hypertension during pregnancy. The only effective treatment, once the complications are established, is usually stopping the pregnancy and delivering the placenta. The preventive treatment of these complications is therefore an important axis in the improvement of maternal and perinatal health.
Due to the very high risk of superimposed PE in chronic hypertensive patients and despite the lack of objective evidence of the effectiveness of low-dose aspirin in the prevention of superimposed PE in this population, the NICE (National Institute for Health and Care Excellence), associated with the Royal College of Gynecology-Obstetrics, recommends since 2010-2011 the use of low-dose aspirin in the prevention of this complication in chronic hypertensive pregnant women; then it was followed by the "U.S. Preventive Services Task Force (USPTF)" in 2014. Recently, the American College of Obstetrics and Gynecology (ACOG) adopted the suggestions of the USPTF and issued the same recommendations in 2018. The French college of obstetric (CNGOF: National College of French Gynecologists and Obstetricians), however, does not recommend the use of low-dose aspirin in pregnant chronic hypertensive women because of insufficient data.
Indeed, although the efficacy of low-dose aspirin is assumed in patients with previous PE, few studies have evaluated its efficacy in patients with chronic hypertension. Moreover, most of the controlled prospective studies using very low doses of aspirin (less than 100 mg) and starting after 20 weeks of gestation do not seem conclusive. For these reasons, the investigators propose to conduct a prospective randomized double-blind placebo-controlled trial to analyze the effectiveness of aspirin dosed at 150 mg and introduced before 20 weeks of gestation in women with chronic hypertension.
The primary endpoint is a maternal and perinatal composite morbidity and mortality including superimposed PE, intrauterine growth restriction, preterm delivery < 37 weeks of gestation, placental abruption, perinatal death, or maternal death.
The definition of superimposed PE in our study is the appearance of significant proteinuria in a chronic hypertensive pregnant woman.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
The treatment will be administered double blind. Pouches or tablets and caskets will be indistinguishable, prepared in advance and made available to pharmacies in participating hospitals by the sponsor. The treatment boxes are given as the monthly visits to the patient, a reassignment box will be required on the server at each visit to obtain a new cabinet number. The cabinet number (detachable label) used at each visit will be reported in the patient's file.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant patient between 10 and 19 weeks of gestation + 6 days
- •Chronic hypertension, whether treated or not, know before pregnancy or diagnosed before randomization
- •Singleton pregnancy
- •Signed the written informed consent
- •Affiliation to social security
排除标准
- •---Medical history requiring anticoagulation (antiphospholipid syndrome, deep vein thromboembolic disease, pulmonary embolism, atherothrombosis, patient with mechanical heart valves),
- •Patient receiving aspirin for another indication outside pregnancy,
- •Patient with significant proteinuria (> 300mg/24 hours or a proteinuria/creatininuria ratio ≥ 30mg/mmol),
- •Active bleeding,
- •History of severe PE with delivery < 34 weeks of gestation,
- •Hypersensitivity to salicylates such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs),
- •Platelet count lower than 100,000 cells/microliter (dosage less than 6 months old),
- •Hemostasis disorders, including hemophilia (with thrombocytopenia)
- •Any constitutional or acquired hemorrhagic disease, (including digestive hemorrhages, history of hemorrhagic stroke and thrombocytopenia
- •Human immunodeficiency virus, or hepatitis B virus, or hepatitis C virus positive serum,
- •Patient included in another interventional study which could interfere with the results of the study,
- •Age <18 years old,
- •Women under the protection of justice,
- •Patients with psychiatric follow-up, poor understanding of French or cognitive problems,
- •Duodenal ulcer,
- •Severe renal impairment,
- •Severe hepatic insufficiency,
- •Severe cardiac impairment,
- •Patients with known glucose-6-phosphate dehydrogenase deficiency,
研究组 & 干预措施
Aspirin 150 mg
Aspirin 150 mg / day (acetylsalicylic acid) once daily in the evening
干预措施: Aspirin 150 mg (Drug)
Placebo
Placebo taken in the evening
干预措施: Placebo (Drug)
结局指标
主要结局
Composite morbidity-mortality criterion including preeclampsia, intra-uterine growth retardation <10th percentile, placental abruption, Preterm birth < 37 weeks of gestation, Perinatal death, Maternal death
时间窗: 9 months
A composite morbidity-mortality criterion that includes the occurrence during pregnancy or postpartum of at least one of the following events: preeclampsia, IUGR \<10th percentile, placental abruption, Preterm birth \< 37 weeks of gestation, Perinatal death (death from 22 weeks of gestation until 28 days after birth), Maternal death
次要结局
- Placental abruption(9 months)
- Preterm delivery(8 months)
- IUGR (< 10th percentile of birth weight)(9 months)
- Preterm birth < 37 weeks of gestation(9 months)
- Fetal loss(5 months)
- Subgroups analysis(9 months)
- Maternal death(9 months)
- Intrauterine growth restriction (IUGR)(9 months)
- Adherence(8 months)
- Angiogenic profile(9 months)
- Child development(4 years)
- Severe pre-eclampsia(9 months)
- Fetal death(5 months)
- Neonatal death(9 months)
- Neonatal morbidity(9 months)
- Toxicity of aspirin(8 months)
- Biological response to the treatment(4 months)