Health TrialsbyHealthPanel

Predictors of Aspirin Failure in Preeclampsia Prevention

ConditionPreeclampsia
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorRockefeller University

About this trial

Hypertensive disorders of pregnancy (including preeclampsia) are among the leading causes of pregnancy complications and maternal deaths worldwide. They also increase the risks to the babies. Numerous interventions have been suggested in order to reduce the rate of preeclampsia. Low-dose aspirin is the most beneficial prophylactic approach in this regard. Nevertheless, aspirin failure is not uncommon. The genetic, laboratory, and clinical factors associated with low-dose aspirin failure in the prevention of preeclampsia are largely unknown. The presence of a genetic variant in PAR4 receptor expressed on platelets, is associated with increased platelet function and possibly with aspirin failure.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Women aged 18-45 years with prior history of preeclampsia who received low dose aspirin in their subsequent gestation and either did or did not have a recurrence of preeclampsia.

Aspirin was given in their subsequent pregnancy in a 81 mg dose prior to 16 weeks of gestation, and was taken with a self-reported compliance rate of at least 80%

Subsequent pregnancy lasted beyond 20 weeks of gestation

Willingness to abstain from non-prescription non-steroidal anti-inflammatory drugs (NSAIDs), which are known to interfere with platelet function assays, for one week prior to platelet function analyses.

Disqualifiers

Age <18 years or >45 years

Any clinically significant adverse reaction to aspirin on prior exposure

Known bleeding disorder based on personal or family history

History of kidney or liver impairment

Trial design

Design model

Parallel

Treatments tested in this trial

  • Aspirin

    Drug

    Platelet assays including VerifyNow Aspirin assay, VerifyNow Base assay, platelet aggregometry, Thromboxana A2 levels- will be measured at baseline and 1 hour after administration of single-dose enteric-coated 81 mg aspirin

Treatment groups

130 Participants
are divided into 2 treatment groups
Group A: Women with prior history of preeclampsia who received aspirin in subsequent gestationExperimental treatment 1 intervention
Group B: Healthy volunteersNo intervention 0 interventions

Trial outcomes

Primary outcomes

1

Allelic frequency of the PAR4 variant (rs773902) in relation to aspirin success in preeclampsia prevention

We will compare the the allelic frequency of the PAR4 variant (rs773902) between aspirin-responders (no recurrence of preeclampsia) and aspirin non responders (recurrence of preeclampsia despite aspirin)

Time frame
At study enrollment

Secondary outcomes

1

Platelet response to aspirin as assessed by VerifyNow Aspirin Assay in relation to aspirin success in preeclampsia prevention-measured as VerifyNow Reaction Units

In the VerifyNow aspirin assay- arachidonic acid is used as the activator to measure the response of the platelet to aspirin. Aspirin irreversibly inhibits COX-1, the enzyme that catalyzes the first reaction leading to the conversion of arachidonic acid to thromboxane A2, which in turn, activates the GPIIb/IIIa receptor to bind fibrinogen, which leads to platelet aggregation. In the presence of aspirin the aggregation does not occur. This assay will demonstrate whether those who developed preeclampsia despite aspirin administration, have increased platelet aggregation at baseline, at 1 hour following aspirin administration, or both.

Time frame
0 and 1 hours post single dose 81 mg enteric-coated aspirin
2

Platelet response to aspirin as assessed by VerifyNow Base Assay in relation to aspirin success in preeclampsia prevention-measured as VerifyNow Reaction Units

In the VerifyNow Base assay, platelet activation is produced by PAR1 thrombin receptor activating peptide + a PAR4 agonist peptide. Thus, this assay will be used to assess whether there is an enhanced response of the PAR4 peptide in those with the PAR4 variant, or perhaps even in those who did not have a good response to aspirin even if they do not have the variant.

Time frame
0 and 1 hours post single dose 81 mg enteric-coated aspirin
3

Platelet response to aspirin as assessed by aggregometry in relation to aspirin success in preeclampsia prevention-measured as VerifyNow Reaction Units

As in the VerifyNow Base assay, the Base channel includes both PAR1 and PAR4 agonists, we will also perform platelet aggregometry with just the PAR4 agonist peptide, to avoid any confounding effect of the PAR1 peptide. This will be measured at baseline and at 1 hour after aspirin administration. Results will be compared between those who developed preeclampsia depicted aspirin and those who did not experience preeclampsia under aspirin prophylaxis.

Time frame
0 and 1 hours post single dose 81 mg enteric-coated aspirin
4

Thromboxane A2 levels in relation to aspirin success in preeclampsia prevention-measured in ng/mL

Aspirin inhibits the enzyme COX-1 which converts arachidonic acid to thromboxane A2. Therefore, evaluating the end product directly-thromboxane A2 levels-may potentially detect differences between the groups (aspirin responders vs. aspirin non-responders).

Time frame
0 and 1 hours post single dose 81 mg enteric-coated aspirin

Other outcomes

Sponsors and contacts

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Rockefeller University

Lead sponsor

Source ClinicalTrials.gov
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