Aspirin Versus Clopidogrel Effect on Uterine Blood Flow in Women With Unexplained Recurrent Miscarriages
Information source: Ain Shams University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Recurrent Pregnancy Loss
Intervention: Aspirin (Drug); Clopidogrel (Drug)
Phase: Phase 2/Phase 3
Status: Active, not recruiting
Sponsored by: Ain Shams University Official(s) and/or principal investigator(s): Mohamed I Ellaithy, M.D., Principal Investigator, Affiliation: Ain Shams University
Summary
The study will compare the effect of Aspirin versus clopidogrel effect on uterine perfusion
in women with unexplained recurrent pregnancy loss with decreased uterine artery pulsatility
index.
Null hypothesis: Women with recurrent miscarriage have the same blood flow after aspirin or
clopidogrel treatment compared to their uterine artery pulsatility index before treatment.
Clinical Details
Official title: Aspirin Versus Clopidogrel Effect on Uterine Perfusion in Women With Unexplained Recurrent Pregnancy Loss With Decreased Uterine Artery Pulsatility Index: A Randomized Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
Primary outcome: Improvement in uterine artery pulsatility index
Secondary outcome: Improvement in subendometrial blood flow
Detailed description:
Recurrent miscarriage has been associated with genetic, anatomic, endocrine, immunologic,
behavioral, environmental factors and prothrombotic states; however, almost 50% of cases of
recurrent miscarriage are unexplained.
Angiogenesis and uterine blood supply are essential for both endometrial growth and embryo
development. As a result, endometrial vascularity has been considered to play a critical
role in endometrial receptivity formation and pregnancy maintenance. The development of
three-dimensional (3D) ultra-sonography with power Doppler angiography provides an objective
and reproducible way to determine endometrial-subendometrial vascularity , which may
evaluate quantitatively the uterine vascularity microenvironment for the developing embryo.
Few studies have shown the application of 3D-power Doppler angiography in assessment of
pregnancy loss.
The rationale behind the use of aspirin is that this substance, at low doses, produces a
vasodilatatory effect by shifting the TXA2/PGI2 ratio toward the dominance of PGI2 activity
through the inhibition of TXA2 production. TXA2 is synthesized mainly by platelets and
induces platelet aggregation and vasoconstriction, whereas PGI2, produced at the level of
vascular endothelial cells, inhibits platelet aggregation and promotes vasodilatation.
Aspirin, at low doses, has been proven to produce the selective inhibition of TXA2
production. In fact, TXA2 is primarily produced by the activity of cyclooxygenase
prostaglandin synthase-1 (COX-1) at the platelet level, which is highly sensitive to aspirin
inhibition. In contrast, PGI2 is mainly synthesized in the endothelial cells through the
activity of both COX-1 and COX-2, which is insensitive to aspirin administration at low
doses. Therefore, the administration of aspirin at low doses reduces TXA2 production without
affecting PGI2 secretion. It is reasonable that the increased PGI2 vasodilatation activity
can enhance uterine perfusion, thereby improving reproductive outcome. In addition, it has
been hypothesized that aspirin administration can reduce TXA2 endometrial cell excretion. It
is known that TXA2 levels at the site of embryo implantation are crucial for the success of
pregnancy. The presence of lower endometrial cell TXA2 production has been demonstrated in
patients who became pregnant with respect to those who did not achieve pregnancy. For these
reasons, low dose Aspirin supplementation is currently considered as an effective and safe
treatment option in the prevention of several pregnancy complications.
Nevertheless, aspirin even when administered at low doses can cause gastrointestinal
bleeding, as reported in studies using 30-50 mg daily. In addition, it has not been proved
that enteric-coated or buffered aspirin is less likely to cause gastrointestinal bleeding
than normal aspirin.
The search for active anti-platelet drugs within the original chemical class of the
thienopyridines, led to the discovery of clopidogrel, a novel ADP-selective agent whose
anti-aggregating properties are several times higher than those of ticlopidine. The
anti-aggregating properties of this compound are well known and, very recently, new results
have clarified its mechanism of action.
Clopidogrel is active only after intravenous or oral administration, and no circulating
activity has been found in the plasma of treated animals or human volunteers.
Experiments in rats have demonstrated that the anti-aggregating activity was caused by a
short lasting metabolite generated in the liver by a cytochrome P450-dependent pathway. The
anti-aggregating property of clopidogrel is caused by an inhibition of the binding of ADP to
its platelet receptors, and more specifically to the low affinity receptors, the high
affinity binding sites being unaffected by clopidogrel. Several events in the ADP activation
process, including adenylyl cyclase down-regulation, protein tyrosine phosphorylation,
activation of the GPIIb-IIIa complex, fibrinogen binding, aggregation and release, were
inhibited by clopidogrel and indicate their close relationship with the activation of a low
affinity receptor by ADP. Thus, clopidogrel is not only a potent antithrombotic drug in
humans but also a good tool to study the effect of ADP on platelets.
The purpose of this study is to compare the effect of Aspirin versus clopidogrel effect on
uterine perfusion in women with unexplained recurrent pregnancy loss with decreased uterine
artery pulsatility index.
Eligibility
Minimum age: 20 Years.
Maximum age: 35 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Women aged between 20 to 38 years old.
- Regular menstrual cycle (26 to 33 days).
- Women with 2 or more previous unexplained first trimester miscarriage.
- Impaired uterine perfusion (PI of uterine artery more than 2. 5).
Exclusion Criteria:
- Known hypersensitivity to any of study medication components.
- Immunotherapy, endocrinotherapy, anticoagulant or anti-platelet management during the
past 3 months
Locations and Contacts
Ain Shams University, Abbasiya, Cairo 11566, Egypt
Additional Information
Starting date: March 2012
Last updated: August 6, 2013
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