Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia

Evaluation of Dose-response Effect of Acetylsalicylic Acid on Placental Development, Preterm Birth, Fetal Growth and Hypertension in Pregnancy in Women With Previous History of Preeclampsia

Placental insufficiency is the source of preeclampsia (PE) and intrauterine growth retardation (IUGR). Current data demonstrate a significant beneficial effect of prophylactic use of aspirin on the recurrence of placental insufficiency and its complications, mainly preeclampsia, when started early in pregnancy. However, there is a significant heterogeneity in medical practice in Canada and around the world in terms of the dose of aspirin used.

The objectives of this study are: 1) Evaluate whether a dose of 160 mg of aspirin is associated with greater improvement in placental function assessed by biochemistry (sFlt-1 and endoglin) and ultrasound (uterine artery Doppler) than a dose of 80 mg in women with a history of PE, 2) Assess whether the change is dependent on platelet aggregation measured by a test used in several Canadian centers (PFA-100).

Study Overview

• Status: Completed
• Conditions: Premature Birth; Pre-Eclampsia; Fetal Growth Retardation; Placental Insufficiency
• Intervention / Treatment: Drug: Acetylsalicylic Acid 160 mg; Drug: Acetylsalicylic Acid 80 mg

Detailed Description

Many studies suggest that aspirin (acetylsalicylic acid) at low dose significantly reduces the incidence of preeclampsia. More recent data have shown that, when administered before 16 weeks of pregnancy, aspirin can prevent over 50% of preeclampsia, severe preeclampsia, and IUGR but also a significant proportion of the rate of preterm births. Current data also demonstrate a beneficial effect of prophylactic use of aspirin when started early in pregnancy in populations composed of high-risk patients with a history of preeclampsia and / or other pregnancy complications related to poor placental function.

Beside, many clinicians are already using aspirin in the context of a proven benefit. However, the usual dose prescribed in Canada today is 80 mg while the most favorable studies have used a slightly higher dose of aspirin (100 mg).

Moreover, it has been demonstrated that the time of day during which aspirin was administered was also a very important factor regarding the effect on blood pressure and adverse outcomes of the majority of pregnancy. Yet the majority of studies in this context have not specified the time of day at which aspirin was or had been taken, possibly underestimating the effect thereof.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G2
    • Centre Hospitalier Universitaire de Québec (CHUQ)/Pavillon CHUL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gestational age between 10 0 / 7 and 13 6 / 7 weeks
• History of preeclampsia (as defined by The Society of Obstetricians and Gynaecologists of Canada) confirmed by medical records

Exclusion Criteria:

• Negative Fetal Heart
• Multiple pregnancy
• Anaphylactic allergy to lactose
• Kown coagulopathy (antithrombin III deficiency, factor V Leiden, antiphospholipid syndrome, the prothrombin mutation, deficiency of protein S or protein C)
• Use of heparin or other anticoagulants.
• Contraindications to aspirin
• Severe fetal abnormality (cystic hygroma, nuchal translucency> 95th percentile, anencephaly, etc.)
• History or active peptic ulcer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Acetylsalicylic Acid 160mg administered at bedtime	Drug: Acetylsalicylic Acid 160 mg; Capsule containing Acetylsalicylic Acid 160mg pill with lactose; Other Names: ASA; Aspirin; Asaphen
Active Comparator: Group B; Acetylsalicylic Acid 80mg administered at bedtime	Drug: Acetylsalicylic Acid 80 mg; Capsule containing Acetylsalicylic Acid 80mg pill with lactose; Other Names: ASA; Aspirin; Asaphen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placental function	We chose a continuous intermediate variable focused on the aetiology, the placental function, assessed by Doppler ultrasound: the average pulsatility index of uterine arteries (UTAP - primary outcome) at 22 weeks of gestation	22nd week of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of pregnancy complications related to placental insufficiency (preeclampsia, IUGR, premature birth)	The effectiveness of treatment on the rate of preterm delivery, hypertensive disorders of pregnancy and IUGR will also be measured by reviewing medical records. All cases with a diagnosis of preterm labor, gestational hypertension or IUGR <10th percentile will be reviewed by a specialist in maternal fetal medicine at blindness for allocation.	At delivery

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Investigators: Principal Investigator: Emmanuel Bujold, MD, MSc, CHU de Quebec-Universite Laval

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: April 1, 2011
• First Submitted That Met QC Criteria: May 10, 2011
• First Posted (Estimate): May 11, 2011

Study Record Updates

• Last Update Posted (Actual): November 13, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Obstetric Labor Complications; Placenta Diseases; Obstetric Labor, Premature; Hypertension, Pregnancy-Induced; Growth Disorders; Premature Birth; Eclampsia; Pre-Eclampsia; Fetal Growth Retardation; Placental Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: C10-11-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided