Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia - Full Text View

Purpose

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).

Condition	Intervention	Phase
Pre-Eclampsia Fetal Growth Retardation Premature Birth Placental Insufficiency	Drug: Acetylsalicylic Acid	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: preeclampsia

Drug Information available for: Aspirin

Genetic and Rare Diseases Information Center resources: Eclampsia

U.S. FDA Resources

Further study details as provided by Centre Hospitalier Universitaire de Québec, CHU de Québec:

Primary Outcome Measures:

Placental function [ Time Frame: 22nd week of gestation ] [ Designated as safety issue: No ]
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

Secondary Outcome Measures:

Rates of pregnancy complications related to placental insufficiency (preeclampsia, IUGR, premature birth) [ Time Frame: At delivery ] [ Designated as safety issue: No ]
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.


Enrollment:	104
Study Start Date:	September 2011
Estimated Study Completion Date:	December 2015
Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group A Acetylsalicylic Acid 160mg administered at bedtime	Drug: Acetylsalicylic Acid Capsule containing Acetylsalicylic Acid 160mg pill with lactose Other Names: Asaphen Aspirin ASA
Active Comparator: Group B Acetylsalicylic Acid 80mg administered at bedtime	Drug: Acetylsalicylic Acid Capsule containing Acetylsalicylic Acid 80mg pill with lactose Other Names: Asaphen Aspirin ASA

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352234

Locations


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

Sponsors and Collaborators

Centre Hospitalier Universitaire de Québec, CHU de Québec

Investigators


Principal Investigator:	Emmanuel Bujold, MD, MSc	Centre Hospitalier Universitaire de Québec, CHU de Québec

More Information

No publications provided


Responsible Party:	Centre Hospitalier Universitaire de Québec, CHU de Québec
ClinicalTrials.gov Identifier:	NCT01352234 History of Changes
Other Study ID Numbers:	C10-11-108
Study First Received:	April 1, 2011
Last Updated:	February 2, 2015
Health Authority:	Canada: Health Canada

Additional relevant MeSH terms:


Fetal Growth Retardation Placental Insufficiency Fetal Diseases Growth Disorders Pathologic Processes Placenta Diseases Pregnancy Complications Aspirin Analgesics Analgesics, Non-Narcotic Anti-Inflammatory Agents Anti-Inflammatory Agents, Non-Steroidal Antipyretics Antirheumatic Agents	Cardiovascular Agents Central Nervous System Agents Cyclooxygenase Inhibitors Enzyme Inhibitors Fibrin Modulating Agents Fibrinolytic Agents Hematologic Agents Molecular Mechanisms of Pharmacological Action Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Platelet Aggregation Inhibitors Sensory System Agents Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015