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

April 3, 2024 updated by: Dr. Graeme Smith

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study will be a prospective, randomized, controlled, double-blinded, single-centre trial with two parallel groups. The primary outcome will be endothelium-dependent vasodilation as measured by iontophoresis and laser speckle contrast imaging (LSCI).

Participants will be recruited following a preeclamptic delivery at Kingston Health Sciences Center. Following confirmation of eligibility, they will be randomized to treatment or control groups. Randomization will be performed as block randomization with a 1:1 allocation ratio. In total, 44 participants will be recruited and randomized, with 22 being assigned to each treatment arm.

Prior to discharge from the hospital, investigators will assess both vascular functional and biochemical variables in each participant. Using LSCI, a non-invasive imaging modality, investigators will continuously measure microvascular blood flow in the volar forearm in response to dilute drug solutions administered using iontophoresis. Iontophoresis refers to the non-invasive administration of drugs under the influence of an applied current. Iontophoresis of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, will occur, the response to which will be recorded using LSCI.

At the study outset, investigators will record additional biophysical parameters such as blood pressure, weight, and BMI. Blood will be drawn and serum analysis of lipid profile, fasting glucose, high sensitivity C-reactive protein, s-Flt-1, platelet-derived growth factor, and uric acid will occur. Urine will be collected for analysis of albumin: creatinine ratio. Findings will then be integrated to calculate a lifetime cardiovascular risk score, which is used to categorize individuals as low risk or high risk.

Study participants who are assigned to the oral aspirin arm of the study will receive 81 mg oral aspirin. Over-encapsulated 81mg aspirin tablets will be used. Study participants in this arm will take 81mg aspirin daily for 6 months. A standard placebo pill, the same size, shape, and color of the oral aspirin will also be used. The placebo will be administered to the participants randomized to the placebo group in the same manner the oral aspirin would be administered - they will take the pill daily for 6 months.

On a monthly basis, all participants will be contacted by study personnel to confirm that they have been taking their medication, and that there are no adverse effects to report.

In addition to either LD-ASA or placebo, both groups will receive our center's current standard of care of cardiovascular assessment and lifestyle counseling at the Maternal Health Clinic (MHC) at Kingston Health Sciences Center. MHC appointments take place at 6 months postpartum. At the MHC appointment, vascular reactivity testing will occur again, followed by biochemical analyses, to assess vascular functional recovery due to the drug.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Queen's University Department of Obstetrics and Gynecology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PO LD-ASA
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
81 mg of low dose aspirin PO for 6 months
Placebo Comparator: PO Placebo
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
placebo PO for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelium-Dependent Dilation
Time Frame: Immediate Postpartum to 6 Months Postpartum
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelium-Independent dilation
Time Frame: Immediate Postpartum to 6 Months Postpartum
Changes in endothelium-independent 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
Blood Pressure
Time Frame: 6 months postpartum
Blood pressure will be taken as the average of five consecutive measurements using an automated controller (BPTru).
6 months postpartum
Body Mass Index
Time Frame: 6 months postpartum
Height and weight will be measured at 6 months postpartum and body mass index will be calculated.
6 months postpartum
Concentration of Serum sFlt-1
Time Frame: 6 months postpartum
A serum blood sample will be taken and sFlt-1 levels will be analysed in our basic science lab.
6 months postpartum
Concentration of Placental Growth Factor
Time Frame: 6 months postpartum
A serum blood sample will be taken and placental growth factor levels will be analysed in our basic science lab.
6 months postpartum
High Sensitivity C-Reactive Protein
Time Frame: 6 months postpartum
A serum blood sample will be sent to our hospital lab. A clinical level of high sensitivity c-reactive protein will be measured.
6 months postpartum
Uric Acid Levels
Time Frame: 6 months postpartum
A serum blood sample will be sent to our hospital lab. A clinical level of uric acid will be measured.
6 months postpartum
Total Cholesterol
Time Frame: 6 months postpartum
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including total cholesterol.
6 months postpartum
High Density Lipoprotein
Time Frame: 6 months postpartum
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including high density lipoprotein.
6 months postpartum
Low Density Lipoprotein
Time Frame: 6 months postpartum
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including low density lipoprotein.
6 months postpartum
Triglycerides
Time Frame: 6 months postpartum
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including triglycerides.
6 months postpartum
Urine Albumin Creatinine Ratio
Time Frame: 6 months postpartum
A urine sample will be collected and sent to our hospital lab. A clinical urine albumin creatinine ratio will be measured.
6 months postpartum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr. Graeme Smith

Investigators

  • Principal Investigator: Graeme N Smith, MD, PhD, Queen's Department of Obstetrics and Gynaecology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 14, 2020

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

January 9, 2020

First Submitted That Met QC Criteria

January 24, 2020

First Posted (Actual)

January 28, 2020

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 3, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OBGY-43312-20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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