Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy (CHASAP)

Centre Hospitalier Intercommunal Creteil

Status and phase: Enrolling; Phase 3

Conditions: Chronic Hypertension Complicating Pregnancy; Pre-Eclampsia; Perinatal Death; Intrauterine Growth Restriction; Placental Abruption; Aspirin

Treatments: Drug: Aspirin 150 mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04356326

2018-004160-58 (EudraCT Number)

CHASAP

Details and patient eligibility

About

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.

Full description

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.

In a secondary analyze, the statistician will use the new definition of superimposed PE that does not require the mandatory presence of proteinuria but the association of chronic hypertension and the appearance of neurological signs (eclampsia, persistent headache, visual disturbances, severe nausea or vomiting), pulmonary edema, persistent epigastric pain, thrombocytopenia <100000 platelets/µL, liver enzymes at 2 times normal, renal insufficiency ( serum creatinine ≥ 97 μmol/L or 1.1 mg/dL,) or a doubling of serum creatinine in the absence of chronic renal disease or significant proteinuria after 20 weeks of gestation or postpartum.

Significant proteinuria is defined as greater than 300 mg/24 hours or when the ratio proteinuria/ creatininuria is ≥ 30 mg/mmol (ratio to 0.3 if all are in mg/dL), in a non-proteinuric women with no urinary tract infection.

Enrollment: 500 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• ---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,
• Gout,
• Patients with known glucose-6-phosphate dehydrogenase deficiency,

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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500 participants in 2 patient groups, including a placebo group

Aspirin 150 mg

Experimental group

Description:

Aspirin 150 mg / day (acetylsalicylic acid) once daily in the evening

Treatment:

Drug: Aspirin 150 mg

Placebo

Placebo Comparator group

Description:

Placebo taken in the evening

Treatment:

Drug: Placebo