Preeclampsia SevereEarly Phase 1PAPVASCNCT04243278
Postpartum Low-Dose Aspirin After Preeclampsia for Optimization of Cardiovascular Risk (PAPVASC)
A Early Phase 1 study testing Low-dose aspirin in people with Preeclampsia Severe and Cardiovascular Diseases, run by Dr. Graeme Smith at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Preeclampsia Severe, Cardiovascular Diseases, Primary Prevention
- What is being tested?
- Low-dose aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- 14 Sep 2020to 31 Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥ 110 mmHg on 2 occasions at least 4 hours apart
- new-onset cerebral or visual disturbance
- severe persistent right upper quadrant pain or serum transaminase concentrations ≥ 2 times the upper limit of normal
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- thrombocytopenia (platelets < 100 x 109/L)
- renal insufficiency (serum creatinine > 97.2 umol/L)
- pulmonary edema
- A singleton gestation
- Gestation between 24+0/7 to 40+6/7 weeks.Exclusion Criteria:
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Queen's University Department of Obstetrics and Gynecology
Kingston, Ontario, K7L 2V7
About this study
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.
Read the 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.
- Being tested
- Low-dose aspirin, Placebo oral tablet
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose aspirinDrug
81 mg of low dose aspirin PO for 6 months
Placebo oral tabletDrug
placebo PO for 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Immediate Postpartum to 6 Months Postpartum
Secondary outcomes (12)
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.
Measured: Immediate Postpartum to 6 Months Postpartum
Blood Pressure
Blood pressure will be taken as the average of five consecutive measurements using an automated controller (BPTru).
Measured: 6 months postpartum
Body Mass Index
Height and weight will be measured at 6 months postpartum and body mass index will be calculated.
Measured: 6 months postpartum
Concentration of Serum sFlt-1
A serum blood sample will be taken and sFlt-1 levels will be analysed in our basic science lab.
Measured: 6 months postpartum
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.
Measured: 6 months postpartum
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.
Measured: 6 months postpartum
Uric Acid Levels
A serum blood sample will be sent to our hospital lab. A clinical level of uric acid will be measured.
Measured: 6 months postpartum
Total Cholesterol
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including total cholesterol.
Measured: 6 months postpartum
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.
Measured: 6 months postpartum
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.
Measured: 6 months postpartum
Triglycerides
A serum blood sample will be sent to our hospital lab. A clinical lipid profile will be measured, including triglycerides.
Measured: 6 months postpartum
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.
Measured: 6 months postpartum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2020
- Study start14 Sep 2020
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Why it stopped: Poor Recruitment Rates
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preeclampsia SevereStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Graeme Smith
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Graeme Smith, Queen's University
- Investigators
- Graeme N Smith, MD, PhD, Principal investigator, Queen's Department of Obstetrics and Gynaecology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04243278
- Sponsor's protocol ID
- OBGY-43312-20
- Acronym
- PAPVASC
- Status last verified
- Apr 2024
- First submitted
- 9 Jan 2020
- Last updated
- 5 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postpartum Low-Dose Aspirin After Preeclampsia for Optimization of Cardiovascular Risk (PAPVASC)
- ClinicalTrials.gov ID
- NCT04243278
- Acronym / sponsor ID
- PAPVASC / OBGY-43312-20
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor Recruitment Rates
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Dr. Graeme SmithUniversity, hospital or other
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 28 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PO LD-ASA | Experimental | Drug: Low-dose aspirinStudy 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. |
| PO Placebo | Placebo comparator | Drug: Placebo oral tabletA 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. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- A singleton gestation
- Gestation between 24+0/7 to 40+6/7 weeks.Exclusion Criteria:
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose aspirin81 mg of low dose aspirin PO for 6 months | Drug | PO LD-ASA |
| Placebo oral tabletplacebo PO for 6 months | Drug | PO Placebo |
Primary outcome
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.
12 secondary outcomes
Endothelium-Independent dilation
Time frame: Immediate Postpartum to 6 Months Postpartum
Blood Pressure
Time frame: 6 months postpartum
Body Mass Index
Time frame: 6 months postpartum
Concentration of Serum sFlt-1
Time frame: 6 months postpartum
Concentration of Placental Growth Factor
Time frame: 6 months postpartum
High Sensitivity C-Reactive Protein
Time frame: 6 months postpartum
Uric Acid Levels
Time frame: 6 months postpartum
Total Cholesterol
Time frame: 6 months postpartum
High Density Lipoprotein
Time frame: 6 months postpartum
Low Density Lipoprotein
Time frame: 6 months postpartum
Triglycerides
Time frame: 6 months postpartum
Urine Albumin Creatinine Ratio
Time frame: 6 months postpartum
Results and safety
The study was stopped early (reason given: Poor Recruitment Rates). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graeme N Smith, MD, PhD principal investigator
Queen's Department of Obstetrics and Gynaecology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Low-dose aspirin in people with Preeclampsia Severe and Cardiovascular Diseases, run by Dr. Graeme Smith at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor Recruitment Rates). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelium-Dependent Dilation (time frame: Immediate Postpartum to 6 Months Postpartum). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2024.