Trial of Early Screening Test for Pre-eclampsia and Growth Restriction

NCT ID: NCT03674606

Last Updated: 2018-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 546 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-01
• Study Completion Date: 2016-04-13

Brief Summary

A study of aspirin use in pregnancy to prevent high blood pressure and growth restriction of the fetus

Detailed Description

Ischemic placental disease (IPD) is an entity encompassing pre-eclampsia, fetal growth restriction (FGR) and placental abruption and has a combined incidence in pregnancy of 10-15%. Pre-eclampsia is a serious systemic condition affecting 3-5% of pregnancies and is responsible for > 50,000 of maternal deaths annually worldwide. The International Society for the Study of Hypertension in Pregnancy defines pre-eclampsia as gestational hypertension with proteinuria of 300 mg or more in 24 h.

The use of low dose aspirin (LDA) prior to 16-weeks' gestation can prevent the pathological process causing placental disease by altering the balance of prostacyclin and thromboxane; hence preventing spiral artery thrombosis and widespread endothelial dysfunction.

There is extensive evidence, demonstrating the efficacy and safety of LDA for prevention of placental disease in high-risk pregnancies where there are clearly identifiable risk factors. However, there is a paucity of research into its efficacy in low-risk women. Administration of aspirin in pregnancy is associated with absolute risk reductions of 2% to 5% for pre-eclampsia, 1% to 5% for FGR 2% to 4% for preterm delivery with no associated increase in perinatal or maternal morbidity.

Several screening tests have been devised to detect the risk of pre-eclampsia and FGR from the first trimester. One of the most notable is that of The Fetal Medicine Foundation (FMF), UK that have devised an algorithm encompassing uterine artery Doppler pulsatility indices, mean arterial pressure (MAP), the placental biomarkers PAPP-A and PLGF in addition to maternal characteristics, which can detect 96% of cases of pre-eclampsia requiring delivery before 34 weeks and 54% of all cases of pre-eclampsia at a fixed false-positive rate of 10%. The FMF screening test is reserved as a research tool, pending validation within a low-risk population. Thus far it has been externally validated in other studies of unselected women with conflicting results as to sensitivity and specificity for placental disease prediction. Following validation of the FMF screening test in low-risk nulliparous women, which is currently the topic of on-going research, the FMF pre-eclampsia screening test may potentially come into clinical practice in the future. Current guidelines followed within the UK, set by The National Institute for Health and Clinical Excellence advocate screening through history taking and provision of LDA in the presence of one major risk factor or two moderate risk-factors. The American College of Obstetricians and Gynecologists have a similar stance and do not recommend screening to predict pre-eclampsia beyond obtaining an appropriate medical history to evaluate for risk factors. They recommend that any further screening tests beyond this should undergo a cost-effectiveness analysis before being used in routine practice.

It has been postulated that it is more cost-effective to use prophylactic medication, notably aspirin for the prevention of placental disease rather than screening and treating an entire low-risk population. The reason for this is because aspirin is felt to be an effective, affordable and safe treatment in pregnancy.

In light of such evidence, with an emerging novel screening test for pre-eclampsia and the efficacy of LDA for placental disease prevention it may be more clinically effective and affordable to prescribe LDA routinely to all women in their first pregnancy as opposed to being upon the basis of a screening test. To assess this hypothesis a preliminary pilot study is required to determine feasibility, acceptability and statistical power required for such a study. The study proposed is a three-armed parallel, multi-center, open-label randomized control trial (RCT) in low-risk women to determine; (i) the efficacy and (ii) the acceptability of women to take routine LDA, versus no LDA versus LDA on the basis of a pre-eclampsia screening test in their first pregnancy. It can be anticipated that the use of such a three-armed study will aid in determining if it is more acceptable to women and feasible to prescribe LDA routinely compared to not at all, or based on results of a screening test.

Conditions

Pre-Eclampsia; Placenta Diseases; Eclampsia Preeclampsia; Fetal Growth Retardation; Foetal Growth Restriction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Routine low-dose aspirin

Subjects shall receive standard antenatal care as well as taking oral low-dose aspirin from the eligibility visit until 36-week gestation once daily, as prescribed by the research clinician. Fetal Medicine Foundation screening test results from the recruitment visit shall not be disclosed to the participants in this arm.

Group Type: EXPERIMENTAL

Low dose aspirin

Intervention Type: DRUG

One 75 mg aspirin dose taken daily

No aspirin

No low-dose aspirin will be prescribed. Fetal Medicine Foundation screening test results from the recruitment visit shall not be disclosed to the participants in this arm.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Test-indicated low-dose aspirin

The Fetal Medicine Foundation screening test will be used to determine whether a subject is at high risk of developing any pre-eclampsia until 42-week gestation. Participants with risk \> 1:8 must start low-dose aspirin treatment immediately. Participants with a risk \< 1:8 will be excluded.

Group Type: ACTIVE_COMPARATOR

Low dose aspirin

Intervention Type: DRUG

One 75 mg aspirin dose taken daily

Interventions

Low dose aspirin

One 75 mg aspirin dose taken daily

Intervention Type: DRUG

Other Intervention Names

Nu-Seals 75; 75 mg aspirin

Eligibility Criteria

Inclusion Criteria

• Nulliparous women.
• Ability to speak and .read English
• Singleton pregnancy at <14 weeks.
• Willing to sign voluntarily a statement of informed consent to participate in the study.

Exclusion Criteria

• Presence of fetal anomaly at the time of the first trimester scan
• Women with known major risk factors for pre-eclampsia who should already be on Aspirin as per National Institute of Clinical Excellence (NICE) guidance; specifically chronic hypertension, underlying connective tissue, renal or vascular disorder, type 1 diabetes mellitus.
• Under 18 years of age.
• Currently enrolled in other clinical trials.
• Contraindications to Aspirin therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Perinatal Ireland

OTHER

Sponsor Role: collaborator

National Maternity Hospital, Ireland

OTHER

Sponsor Role: collaborator

Royal College of Surgeons, Ireland

OTHER

Sponsor Role: collaborator

University College Dublin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

National Maternity Hospital

Dublin, , Ireland

Rotunda Hospital

Dublin, , Ireland

Countries

Ireland

References

Mone F, Mulcahy C, McParland P, Stanton A, Culliton M, Downey P, McCormack D, Tully E, Dicker P, Breathnach F, Malone FD, McAuliffe FM. An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and growth restriction (TEST): Trial protocol. Contemp Clin Trials. 2016 Jul;49:143-8. doi: 10.1016/j.cct.2016.07.003. Epub 2016 Jul 6.

Reference Type: BACKGROUND

PMID: 27394381 (View on PubMed)

Other Identifiers

2013-004241-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN15191778

Identifier Type: REGISTRY

Identifier Source: secondary_id

TEST_PILOT_V1

Identifier Type: -

Identifier Source: org_study_id