Clinical Trial Details
— Status: Terminated
Administrative data
NCT number |
NCT04243278 |
Other study ID # |
OBGY-43312-20 |
Secondary ID |
|
Status |
Terminated |
Phase |
Early Phase 1
|
First received |
|
Last updated |
|
Start date |
September 14, 2020 |
Est. completion date |
December 31, 2022 |
Study information
Verified date |
April 2024 |
Source |
Queen's University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical 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. 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.
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.