Clinical trial NCT03766594: Sildenafil Citrate in Early Unexplained Recurrent Pregnancy Loss
Official title: Effect of Preconceptional Sildenafil Citrate Treatment in Women With Early Unexplained Recurrent Pregnancy Loss: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Miscarriage, Recurrent
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2018-12-06
Enrollment: 90
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized into two groups: Group (A) folic acid and sildenafil citrate and Group (B) folic acid and placebo.

Folic acid (0.5 mg) will be started 3 months before conception in the two groups. Sildenafil citrate (dose: 25 mg; oral tablets, 4 times/day) or placebo will be started preconception for 24 days
Primary purpose: TREATMENT

Brief summary: Recurrent unexplained spontaneous miscarriage (RSM) is defined as three consecutive pregnancy loss prior to 20 weeks from the last menstrual period. 1% to 2% of women experience RSM. Treatment of URSM is a challenging issue. The currently available lines of treatment according to simplicity of use, reliability and degree of invasiveness include corticosteroids, sildenafil citrate, aspirin, heparin and immunoglobulins (besides good antenatal care), but up to now there are no prospective randomized studies, powerful enough, to determine a significant difference between these therapeutic protocols, with any of the above mentioned pharmacological agents.

Sildenafil Citrate (Viagra®), a vasodilator, is also described as an anti-inflammatory agent. While improving uterine blood flow in the proliferative phase, NO may have detrimental effects at the level of the endometrium during the implantation window. The NO- mediated release of cytokines such as tumour necrosis factor- from activated natural killer cells has been implicated as a cause of implantation failure.

Based on these observations, this study attempts was made to study uterine arteries and sub-endometrial blood flow during the luteal phase in normal fertile women and in patients with Unexplained recurrent miscarriage


Eligibility criteria: Inclusion Criteria:

* Age: 20-35 years.
* BMI (20-30)
* History of three or more successive unexplained recurrent miscarriage.
* Normal uterine cavity by hystrography or hysteroscopy.
* No luteal phase defects by progesterone \> 10 ng.
* Normal thyroid function (TSH, T3, T4)
* Normal lupus anticoagulant measured by activated partial throbmoplastine time (32-43 seconds).
* Normal anticardolipin (IgG \< 20 gpl and IgM \< 15 MPL measured by ELISA).
* Normal anti thyroid antibodies.
* Normal glucouse tolerance test.
* Normal parental karyotyping.

Exclusion Criteria:

* Age\<20 or\>35 year
* BMI\<20 or\>30
* Systemic diseases that might affect pregnancy such as diabetes or thyroid disorders or hypertension.
* History of consanguinity.
* Family history of chromosomal abnormalities (e.g. trisomy 21, trisomy 13, Turner's disease ...etc.).
* History of autoimmune diseases, eg: systemic lupus.
* Congenital anomaly in uterine cavity as bicornate or septate uterus.
* Luteal phase defect and corpus luteum insufficiency.
* Uterine masses as fibroid or polyps.
* Patient with patuoles os.
* patient with antiphosphlipid syndrome.
* Cigarette smoking and alcohol.

Primary outcomes:
measure: Miscarriage rate
timeFrame: 24 gestational weeks
Secondary outcomes:
measure: Uterine artery resistance index
timeFrame: At 24 gestational weeks
measure: Uterine artery pulsatility index
timeFrame: At 24 gestational weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain SHams Maternity Hospital
state: Abbaseya
Study officials:
affiliation: M Yakout
name: Mohamed Yakout, MBBCh
role: PRINCIPAL_INVESTIGATOR
References: