Postpartum Low-Dose Aspirin After Preeclampsia for Optimization of Cardiovascular Risk (PAPVASC)

• Status: Recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: Female

Summary

Women who develop preeclampsia (PE) in pregnancy are at a greater risk for adverse cardiovascular health outcomes. PE is associated with vascular remodeling and functional changes in the postpartum, reflective of its systemic effects during gestation. Aberrant microvascular endothelial function has been demonstrated in pharmacological studies of formerly preeclamptic women. However, clinicians do not have any recourse for modulating vascular functional adaptations nor mitigating the future risk for maternal disease in the early postpartum. Low-dose aspirin (LD-ASA) is commonly prescribed to prevent PE and confers a consistently positive effect on mitigating PE risk when given in early gestation to women at risk. While the precise effect of LD-ASA on PE development is not fully understood, existing evidence suggests it may confer an array of anti-thrombotic, vasodilatory, pro-endothelial effects that mitigate the risk of disease.

This study will be a randomized, placebo-controlled trial of LD-ASA administration over 6 months in the early postpartum in women with prior severe PE. Women will be identified, enrolled, and randomized to either treatment or placebo groups. Treatment groups will receive 81 mg daily oral aspirin, while control groups will receive an equivalent placebo pill. Vascular functional assessment at study outset will take place, combining laser speckle contrast imaging and iontophoresis of dilute vasoactive drug solutions. Blood and urine will be obtained for analysis of cardiometabolic and endothelial factors. Participants will take their assigned study drug for 6 months, after which a retest appointment will take place to assess vascular functional changes.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dr. Graeme Smith
• Treatments: Aspirin

Criteria

Inclusion Criteria:

1. Confirmed severe preeclampsia diagnosed prior to delivery

Preeclampsia defined as: Blood pressure > 140/90 AND proteinuria > 300mg/24 hours OR 2+ on repeat dip stick

Severe Preeclampsia defined as the presence of one or more of the following:

i. systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥ 110 mmHg on 2 occasions at least 4 hours apart

ii. new-onset cerebral or visual disturbance

iii. severe persistent right upper quadrant pain or serum transaminase concentrations ≥ 2 times the upper limit of normal

iv. thrombocytopenia (platelets < 100 x 109/L)

v. renal insufficiency (serum creatinine > 97.2 umol/L)

vi. pulmonary edema

2. A singleton gestation

3. Gestation between 24+0/7 to 40+6/7 weeks.Exclusion Criteria:

Exclusion Criteria:

1. Multiple pregnancy

2. Chronic hypertension or other condition requiring the use of BP-lowering medication

3. Cardiovascular disorders: Unstable angina pectoris, heart failure, life-threatening arrhythmia, atrial fibrillation, kidney failure

4. Known allergy or sensitivity to aspirin used in the study

5. Any medical comorbidity that is a contraindication to LD-ASA: Hemophilia or other bleeding disorder, history of GI bleeding, renal failure, severe liver disease, thrombocytopenia, gout, G6PD deficiency

6. Recent history of drug/alcohol abuse (< 1 year prior to delivery), or receiving treatment for such

7. Nasal polyps

8. Hypercholesterolemia requiring pharmaceutical treatment

9. Raynaud's phenomenon

10. Collagen-vascular disease: lupus, scleroderma, rheumatoid arthritis

11. History of pre-existing diabetes

12. Ongoing use of any of the following medications: methotrexate, anti-coagulants, thrombolytics, oral hypoglycemics, uricsuric agents, valproic acid, glucocorticosteroids, digoxin