Sildenafil Citrate in Early Unexplained Recurrent Pregnancy Loss

NCT03766594 | Completed Phase 1

• 1 other identifier: SURPL
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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

Conditions

Miscarriage, Recurrent

Outcome Measures

Primary Outcomes (1)

• Miscarriage rate

  number of spontaneous/missed miscarriages among the participants in both groups

  24 gestational weeks

Secondary Outcomes (2)

• Uterine artery resistance index

  At 24 gestational weeks

• Uterine artery pulsatility index

  At 24 gestational weeks

Study Arms (2)

Sildenafil group

ACTIVE COMPARATOR

Includes 45 women who received Sildenafil citrate (Respatio(R) 25mg tablets four times daily for 24 days preconceptionally starting first day of previous period) and folic acid (Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally).

Drug: Sildenafil Citrate; Drug: Folic Acid

Control group

ACTIVE COMPARATOR

Includes 45 women who received placebo oral tablets (apparently identical to Respatio(R) 25mg tablets, four times daily for 24 days preconceptionally starting first day of previous period) and folic acid (Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally).

Drug: Folic Acid; Drug: Placebo Oral Tablet

Interventions

Sildenafil Citrate DRUG

Respatio(R) 25mg tablets four times daily for 24 days preconceptionally starting first day of previous period

Sildenafil group

Folic Acid DRUG

Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally

Control group; Sildenafil group

Placebo Oral Tablet DRUG

Placebo tablet apparently identical to Respatio(R) 25mg tablets, taken four times daily for 24 days preconceptionally starting first day of previous period

Control group

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain SHams Maternity Hospital

Cairo, Abbaseya, 002, Egypt

Location

MeSH Terms

Conditions

Abortion, Habitual

Interventions

Sildenafil Citrate; Folic Acid

Condition Hierarchy (Ancestors)

Abortion, Spontaneous; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines

Study Officials

• Mohamed Yakout, MBBCh

  M Yakout

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Patients are randomized to receive either folic acid and sildenafil citrate or folic acid and placebo. Placebo tablets were same size and appearance of the sildenafil citrate tablets.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident of O&G

Model Details: 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

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 6, 2018
• Study Start: January 1, 2018
• Primary Completion: November 20, 2018
• Study Completion: December 1, 2018
• Last Updated: December 6, 2018

Record last verified: 2018-12

Locations

EG (1)