Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial. (GAP)

Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial

Low-dose aspirin started in the first-trimester has been associated with a decrease of preeclampsia, fetal growth restriction and preterm birth in high-risk pregnancies. Multiple pregnancies are considered a risk factor for all those adverse outcomes. The main objective of the current trial is to evaluate whether a dose of 80 mg of aspirin is associated with an improvement of birthweight compared to placebo in twin pregnancies.

Study Overview

• Status: Completed
• Conditions: Premature Birth; Fetal Growth Retardation; Preeclampsia; Infant, Very Low Birth Weight; Small for Gestational Age
• Intervention / Treatment: Drug: Acetylsalicylic Acid; Drug: Placebo

Detailed Description

Twin pregnancies represent approximately 3% of births and are associated with increased risks of complications such as preeclampsia, fetal growth restriction and preterm birth. All of these complications are commonly associated impaired placental function and low birth weight.

Most prophylactic measures tested over the years have failed to prevent these adverse outcomes in twin pregnancies. Since administration of low-dose of aspirin can improve placental function and all these adverse outcomes in high-risk pregnancies, mainly in women with prior adverse outcomes, we suggest that similar benefits could be seen in twins. We are expecting that the administration of low-dose of aspirin starting in the first-trimester in twin pregnancies could lead to an improvement of placental function, a reduction or these adverse perinatal outcomes and therefore to an improvement of birthweight.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1L 3L5
    • Hôpital St-François d'Assise-CHUQ
  • Québec, Canada, G1V 4G2
    • Centre Hospitalier Universitaire de Québec (CHU de Québec)/Pavillon CHUL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gestational age between 8 0/7 and 13 6/7 weeks
• Twin pregnancy confirmed by ultrasound

Exclusion Criteria:

• One or two negative heart beat
• Previous hypertensive disorder of pregnancy
• Pre-existing hypertension or diastolic blood pressure >90 mmHg at randomization
• Pre-existing nephropathy
• Pre-existing diabetes (type 1 or 2)
• Anaphylactic allergy to lactose
• Known 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.
• Contre-indications to aspirin
• Discordance of crown-rump length greater than 20%.
• Fetal anomalies (cystic hygroma, nuchal translucency > 95th percentile, anencephaly, omphalocele, etc.)
• Previous or current gastric 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
Active Comparator: Experimental; Acetylsalicylic Acid 80mg administered daily at bedtime	Drug: Acetylsalicylic Acid; Capsule containing Acetylsalicylic Acid 80mg pill with lactose; Other Names: ASA; Aspirin; Asaphen
Placebo Comparator: Control; Identical placebo administered daily at bedtime	Drug: Placebo; Capsule containing placebo pill with lactose; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Birth weight	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low birth weight	(birthweight below 2,500 grams)	At delivery
Very low birth weight	(birthweight below 1,500 grams)	At birth
Fetal growth restriction	(birthweight below the 10th or 3rd percentile for gestational age)	16-18 and 22-24 weeks
Preterm birth	(delivery before 37 weeks)	At delivery
Very preterm birth	(delivery before 34 weeks)	At delivery
Preeclampsia	(according to American College of Obstetricians and Gynecologists 2014 guidelines definition)	At delivery
Early-onset preeclampsia	(onset of preeclampsia before 34 weeks)	At delivery
UtA_PI	Mean uterine artery pulsatility index	22-24 weeks
Aspirin resistance	(PFA-100 below 150)	16-18 and 22-24 weeks
Cervical length		22-24 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: October 29, 2014
• First Submitted That Met QC Criteria: October 29, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): November 9, 2018
• Last Update Submitted That Met QC Criteria: November 7, 2018
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Pregnancy Complications; Twin Pregnancy
• Additional Relevant MeSH Terms: Pathologic Processes; Body Weight; Fetal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Hypertension, Pregnancy-Induced; Growth Disorders; Premature Birth; Birth Weight; Pre-Eclampsia; Fetal Growth Retardation; 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: 2014-1817