Miscarriage, RecurrentPhase 1NCT03766594
Sildenafil Citrate in Early Unexplained Recurrent Pregnancy Loss
A Phase 1 study testing Sildenafil Citrate and Folic Acid in people with Miscarriage, Recurrent, run by Ain Shams University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 35 years, women only
- Conditions the study is for
- Miscarriage, Recurrent
- What is being tested?
- Sildenafil Citrate and Folic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2018to 1 Dec 2018
- Phase
- 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 20 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Preconceptional Sildenafil Citrate Treatment in Women With Early Unexplained Recurrent Pregnancy Loss: a Randomized Controlled Trial
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
- Being tested
- Sildenafil Citrate, Folic Acid, Placebo Oral Tablet
- Medical subject headings
- Abortion, Habitual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil CitrateDrug
Respatio(R) 25mg tablets four times daily for 24 days preconceptionally starting first day of previous period
Folic AcidDrug
Folic acid(R) 0.5mg tablets once daily for 3 months preconceptionally
Placebo Oral TabletDrug
Placebo tablet apparently identical to Respatio(R) 25mg tablets, taken four times daily for 24 days preconceptionally starting first day of previous period
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Folic Acid; Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Miscarriage rate
number of spontaneous/missed miscarriages among the participants in both groups
Measured: 24 gestational weeks
Secondary outcomes (2)
Uterine artery resistance index
Uterine artery resistance index assessed by uterine artery Doppler study in ongoing pregnancies of both groups
Measured: At 24 gestational weeks
Uterine artery pulsatility index
Uterine artery pulsatility index assessed by uterine artery Doppler study in ongoing pregnancies of both groups
Measured: At 24 gestational weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2018
- Study start1 Jan 2018
- Primary completion20 Nov 2018
- Study completion1 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Miscarriage, RecurrentStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Yakout Mohamed, Ain Shams University
- Investigators
- Mohamed Yakout, MBBCh, Principal investigator, M Yakout
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03766594
- Sponsor's protocol ID
- SURPL
- Status last verified
- Dec 2018
- First submitted
- 5 Dec 2018
- Last updated
- 6 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Preconceptional Sildenafil Citrate Treatment in Women With Early Unexplained Recurrent Pregnancy Loss: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03766594
- Acronym / sponsor ID
- SURPL
- Conditions
- Miscarriage, Recurrent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 20 Nov 2018 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 6 Dec 2018 (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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Sildenafil group | Active comparator | Drug: Sildenafil Citrate, Drug: Folic AcidIncludes 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). |
| Control group | Active comparator | Drug: Folic Acid, Drug: Placebo Oral TabletIncludes 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). |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.).
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 |
|---|---|---|
| Sildenafil CitrateRespatio(R) 25mg tablets four times daily for 24 days preconceptionally starting first day of previous period | Drug | Sildenafil group |
| Folic AcidFolic acid(R) 0.5mg tablets once daily for 3 months preconceptionally | Drug | Control group, Sildenafil group |
| Placebo Oral TabletPlacebo tablet apparently identical to Respatio(R) 25mg tablets, taken four times daily for 24 days preconceptionally starting first day of previous period | Drug | Control group |
Primary outcome
Miscarriage rate
Time frame: 24 gestational weeks
number of spontaneous/missed miscarriages among the participants in both groups
2 secondary outcomes
Uterine artery resistance index
Time frame: At 24 gestational weeks
Uterine artery pulsatility index
Time frame: At 24 gestational weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2018.
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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.
Mohamed Yakout, MBBCh principal investigator
M Yakout
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sildenafil Citrate and Folic Acid in people with Miscarriage, Recurrent, run by Ain Shams University at 1 site in Egypt.
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: finished, as of the sponsor's last update on 6 Dec 2018. 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 Egypt. 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. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Miscarriage rate (time frame: 24 gestational weeks). 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 6 Dec 2018.