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

NCT04243278 | Terminated Early Phase 1 DMC

• 1 other identifier: OBGY-43312-20
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Preeclampsia Severe; Cardiovascular Diseases; Primary Prevention

Outcome Measures

Primary Outcomes (1)

• Endothelium-Dependent Dilation

  Changes in endothelium-dependent dilation from the immediate postpartum period to 6 months postpartum. Measured by laser speckle contrast imaging in conjunction with iontophoresis.

  Immediate Postpartum to 6 Months Postpartum

Secondary Outcomes (12)

• Endothelium-Independent dilation

  Immediate Postpartum to 6 Months Postpartum

• Blood Pressure

  6 months postpartum

• Body Mass Index

  6 months postpartum

• Concentration of Serum sFlt-1

  6 months postpartum

• Concentration of Placental Growth Factor

  6 months postpartum

Study Arms (2)

PO LD-ASA

EXPERIMENTAL

Study participants who are assigned to the oral aspirin arm of the study will receive 81mg oral aspirin. Over-encapsulated 81mg aspirin tablets will be used. Study participants in this arm will take 81mg aspirin daily for 6 months.

Drug: Low-dose aspirin

PO Placebo

PLACEBO COMPARATOR

A standard placebo pill, the same size, shape and color of the oral aspirin will be used. The placebo pills will be over-encapsulated in the same manner as the aspirin tablets. The placebo will be administered to the participants randomized to placebo group in the same manner the oral aspirin would be administered - they will take the pill daily for 6 months.

Drug: Placebo oral tablet

Interventions

Low-dose aspirin DRUG

81 mg of low dose aspirin PO for 6 months

PO LD-ASA

Placebo oral tablet DRUG

placebo PO for 6 months

PO Placebo

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• A singleton gestation

You may not qualify if:

• Multiple pregnancy
• Chronic hypertension or other condition requiring the use of BP-lowering medication
• Cardiovascular disorders: Unstable angina pectoris, heart failure, life-threatening arrhythmia, atrial fibrillation, kidney failure
• Known allergy or sensitivity to aspirin used in the study
• 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
• Recent history of drug/alcohol abuse (\< 1 year prior to delivery), or receiving treatment for such
• Nasal polyps
• Hypercholesterolemia requiring pharmaceutical treatment
• Raynaud's phenomenon
• Collagen-vascular disease: lupus, scleroderma, rheumatoid arthritis
• History of pre-existing diabetes
• Ongoing use of any of the following medications: methotrexate, anti-coagulants, thrombolytics, oral hypoglycemics, uricsuric agents, valproic acid, glucocorticosteroids, digoxin

Sponsors & Collaborators

• Dr. Graeme Smith: lead

Study Sites (1)

Queen's University Department of Obstetrics and Gynecology

Kingston, Ontario, K7L 2V7, Canada

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Graeme N Smith, MD, PhD

  Queen's Department of Obstetrics and Gynaecology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 28, 2020
• Study Start: September 14, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 5, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)