Combined Multi-marker Screening and Treatment With Aspirin for Pre-eclampsia Prevention

Study Overview
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Brief Summary
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Phase III two arm double-blinded randomised controlled trial to examine the effect of prophylactic low-dose aspirin from the first-trimester of pregnancy in women at increased risk for PET on the incidence and severity of the disease

Detailed Description
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Screening and Prevention of Pre-eclampsia (High Blood Pressure): Randomised Trial of Aspirin Versus Placebo (ASPRE) Screening: All women with singleton pregnancies undergoing routine screening for aneuploidies will be invited to participate in the screening study for PET. Interventions: Participants who are screened with a high-risk of developing PET will be randomised into one of 2 arms of the trial (on the same day as screening or within 1 week of the screening visit). Randomised participants will be advised to start 150mg of Aspirin/Placebo once per night within 24 hours of randomisation until 36 weeks' gestation or when signs of labour commence. The maximum duration for aspirin or placebo intake will be 180 days. Key Inclusion and Exclusion Criteria Inclusion criteria for participant selection for RCT Age > 18 years, Singleton pregnancies, Live fetus at 11-13 weeks of gestation, High-risk for preterm-PET at 11-13 weeks by the algorithm combining maternal history and characteristics, biophysical findings (mean arterial pressure and uterine artery Dopplers) and biochemical factors (pregnancy associated plasma protein-A and placental growth factor), English, Italian, Spanish, French, Dutch or Greek speaking (otherwise interpreters will be used), Informed and written consent. Exclusion criteria Multiple pregnancies, Women taking low-dose aspirin regularly (administration must have ceased >28days prior to randomisation), Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks assessment, Women who are unconscious or severely ill, those with learning difficulties, or serious mental illness, Bleeding disorders such as Von Willebrand's disease, Peptic ulceration, Hypersensitivity to aspirin or already on long term non-steroidal anti-inflammatory medication, Age < 18 years, Concurrent participation in another drug trial or at any time within the previous 28 days, Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol.

Official Title
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Combined Multi-marker Screening and Randomised Patient Treatment With Aspirin for Evidence-based Pre-eclampsia Prevention. University College London - Sponsor of All EU Study Sites.

Conditions
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Preeclampsia

Intervention / Treatment
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* Drug: Aspirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Singleton pregnancies Live fetus at 11-13 weeks of gestation, High-risk for preterm-PET at 11-13 weeks by the algorithm combining maternal history and characteristics, biophysical findings (mean arterial pressure and uterine artery Dopplers) and biochemical factors (pregnancy associated plasma protein-A and placental growth factor), English, Italian, Spanish, French, Flemish, Hebrew, Arabic and Russian speaking (otherwise interpreters will be used) Informed and written consent. Exclusion Criteria: Multiple pregnancies Women taking low-dose aspirin regularly Pregnancies complicated by major fetal abnormality identified at the 11-13 weeks assessment Women who are unconscious or severely ill, those with learning difficulties, or serious mental illness, Bleeding disorders such as Von Willebrand's disease Peptic ulceration Hypersensitivity to aspirin or already on long term nonsteroidal anti- inflammatory medication Age < 18 years Concurrent participation in another drug trial or at any time within the previous 28 days Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Placebo | Drug: Placebo<br>* Participants who are screened with a high-risk of developing PET will be randomised into one of 2 arms of the trial (on the same day as screening or within 1 week of the screening visit). Randomised participants will be advised to start 150mg of Aspirin/Placebo once per night within 24 hours of randomisation until 36 weeks' gestation or when signs of labour commence. The maximum duration for aspirin or placebo intake will be 180 days.<br>* Other names: Aspirin;|
| Active Comparator: Intervention Group<br>Aspirin | Drug: Aspirin<br>* Participants who are screened with a high-risk of developing PET will be randomised into one of 2 arms of the trial (on the same day as screening or within 1 week of the screening visit). Randomised participants will be advised to start 150mg of Aspirin/Placebo once per night within 24 hours of randomisation until 36 weeks' gestation or when signs of labour commence. The maximum duration for aspirin or placebo intake will be 180 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Pre-eclampsia requiring delivery prior to 37 weeks of gestation |  | 24-26 Weeks |