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

Primary Purpose

Preeclampsia Severe, Cardiovascular Diseases, Primary Prevention

Status
Recruiting
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Low-dose aspirin
Placebo oral tablet
Sponsored by
Dr. Graeme Smith
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Preeclampsia Severe

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Queen's University Department of Obstetrics and GynecologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

PO LD-ASA

PO Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
January 9, 2020
Last Updated
May 19, 2023
Sponsor
Dr. Graeme Smith
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1. Study Identification

Unique Protocol Identification Number
NCT04243278
Brief Title
Postpartum Low-Dose Aspirin After Preeclampsia for Optimization of Cardiovascular Risk (PAPVASC)
Acronym
PAPVASC
Official Title
Postpartum Low-Dose Aspirin After Preeclampsia for Optimization of Cardiovascular Risk (PAPVASC)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 14, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Graeme Smith

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preeclampsia Severe, Cardiovascular Diseases, Primary Prevention

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PO LD-ASA
Arm Type
Experimental
Arm Description
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.
Arm Title
PO Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Low-dose aspirin
Intervention Description
81 mg of low dose aspirin PO for 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
placebo PO for 6 months
Primary Outcome Measure Information:
Title
Endothelium-Dependent Dilation
Description
Changes in endothelium-dependent dilation from the immediate postpartum period to 6 months postpartum. Measured by laser speckle contrast imaging in conjunction with iontophoresis.
Time Frame
Immediate Postpartum to 6 Months Postpartum
Secondary Outcome Measure Information:
Title
Endothelium-Independent dilation
Description
Changes in endothelium-independent dilation from the immediate postpartum period to 6 months postpartum. Measured by laser speckle contrast imaging in conjunction with iontophoresis.
Time Frame
Immediate Postpartum to 6 Months Postpartum
Title
Blood Pressure
Description
Blood pressure will be taken as the average of five consecutive measurements using an automated controller (BPTru).
Time Frame
6 months postpartum
Title
Body Mass Index
Description
Height and weight will be measured at 6 months postpartum and body mass index will be calculated.
Time Frame
6 months postpartum
Title
Concentration of Serum sFlt-1
Description
A serum blood sample will be taken and sFlt-1 levels will be analysed in our basic science lab.
Time Frame
6 months postpartum
Title
Concentration of Placental Growth Factor
Description
A serum blood sample will be taken and placental growth factor levels will be analysed in our basic science lab.
Time Frame
6 months postpartum
Title
High Sensitivity C-Reactive Protein
Description
A serum blood sample will be sent to our hospital lab. A clinical level of high sensitivity c-reactive protein will be measured.
Time Frame
6 months postpartum
Title
Uric Acid Levels
Description
A serum blood sample will be sent to our hospital lab. A clinical level of uric acid will be measured.
Time Frame
6 months postpartum
Title
Total Cholesterol
Description
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including total cholesterol.
Time Frame
6 months postpartum
Title
High Density Lipoprotein
Description
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including high density lipoprotein.
Time Frame
6 months postpartum
Title
Low Density Lipoprotein
Description
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including low density lipoprotein.
Time Frame
6 months postpartum
Title
Triglycerides
Description
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including triglycerides.
Time Frame
6 months postpartum
Title
Urine Albumin Creatinine Ratio
Description
A urine sample will be collected and sent to our hospital lab. A clinical urine albumin creatinine ratio will be measured.
Time Frame
6 months postpartum

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Gestation between 24+0/7 to 40+6/7 weeks.Exclusion Criteria: Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica Pudwell, MPH, MSc
Phone
613-549-6666
Ext
3937
Email
jessica.pudwell@queensu.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Heather Ramshaw, BSc
Phone
613-548-1372
Email
ramshawh@queensu.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Graeme N Smith, MD, PhD
Organizational Affiliation
Queen's Department of Obstetrics and Gynaecology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Queen's University Department of Obstetrics and Gynecology
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Graeme N Smith, MD,PhD,FRCSC

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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