Miscarriage, RecurrentTiC-RPLNCT03336463
Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score
An observational study of Miscarriage, Recurrent, run by Ferrer inCode, S.L. at 8 sites in 2 countries.
Trial summary
Recurrent pregnancy loss (RPL) is a clinical problem affecting 1-5% of couples of reproductive age. The contribution of thrombophilia to RPL is disputed. This controversy is partly due to low sensitivity of the genetic variants currently used to evaluate hereditary thrombophilia: the Leiden mutation (identified as… Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- Miscarriage, Recurrent
- How many people
- 364 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Feb 2015to Jan 2017
- Phase
- Observational
- 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 18 to 37 years
- Women only
- Adult
Study population: The study will include women with recurrent pregnancy loss (> 2 consecutive or > 3 non-consecutive) before the 20th week of pregnancy (cases) and women with at least 1 pregnancy at term (controls).
Who may be able to join
- Women >18 and < 38 years old at the time of the first pregnancy.
- Women with successful implantation and at least one full-term pregnancy
- No chronic pathology
- Repeated clinical miscarriages and/or foetal death (≥ 2 consecutive or ≥ 3 non- consecutive) before the 20th weeks of pregnancy, from spontaneous or assisted pregnancies.
- Recurrent miscarriage with the same gametic origin.
- Idiopathic origin:
- Women < 38 years old Non-severe seminal factor (sperm concentration > 2 mill/ml) Normal karyotypes in both spouses (or in the male and the donor in the case of ovocyte donation) Antiphospholipid syndrome negative Normal or corrected thyroid function BMI < 30
Who cannot join
- Personal or family history of thrombosis
- Personal history of obstetric complications Miscarriage or foetal death Pre-eclampsia or eclampsia Intrauterine growth restriction Placental abruption
- Concomitant anticoagulant treatment and/or antiplatelet treatments during pregnancy
- CASES
- Diabetes
- Chronic pathologies
- Hydrosalpinx
- Concomitant anticoagulant or antiplatelet treatment
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Spain7 sites
Institut d'Investigació Sant Pau
Barcelona, 08025
Gendiag.exe, S.L.
Esplugues de Llobregat, Select State, 08950
Instituto Salud Carlos III
Madrid, 28029
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008
IVI-RMA Valencia
Valencia, 46015
Instituto de Investigaciones Sanitarias La Fe
Valencia, 46026
About this study
Recurrent pregnancy loss (RPL) is a clinical problem affecting 1-5% of couples of reproductive age. The contribution of thrombophilia to RPL is disputed. This controversy is partly due to low sensitivity of the genetic variants currently used to evaluate hereditary thrombophilia: the Leiden mutation (identified as rs6025) in the coagulation factor 5 (F5L) gene and mutation G20210A (identified as rs1799963) in the prothrombin (PT) gene.
Our objective was to determine whether a wider algorithm that includes clinic and genetic variants associated with thrombophilia could be more useful in the prediction for RPL than FVL and PT alone.
Read the detailed description
Recurrent pregnancy loss can affect up to 5% of women in child-bearing age and is considered one of the most common causes of female sterility. In recent years, the association between thrombophilia and pregnancy failure has been observed in a number of studies, varying according to the nature of the thrombophilia (for example the antiphospholipid syndrome as opposed to the hereditary forms) or the type of pregnancy loss (either isolated or recurrent, or early or late). It has therefore been accepted that thrombophilia is detected in a significant number of idiopathic pregnancy losses, reaching 66% of the cases in some series.
Since the 1990's, a number of studies have associated recurrent pregnancy loss with FVL mutations (most frequently) and G20210 PT. In a systematic review, it was confirmed that women with thrombophilia have a higher risk of developing thromboembolism and complications in pregnancy. Another recent meta-analysis of prospective cohort studies concluded that women who were carriers of FVL had a higher risk of late pregnancy loss, at 52%, as opposed to non-carriers (OR=1.52), though the differences in absolute risk were discreet (4.2% and 3.2%, respectively). However, the analysis of these 2 single nucleotide polymorphisms (SNPs) showed low discriminative capacity and diagnostic sensitivity.
This study hypothesize that the use of the Thrombo inCode® in the screening for hereditary thrombophilia in patients with recurrent pregnancy loss can improve the diagnostic sensitivity and predictive capacity of the routine genetic panel, based on FVL and G20210A PT. Thus, the Thrombo inCode® model can accurately identify more patients with clinical-genetic risk of thromboembolism and therefore establish the appropriate preventive measures.
A transversal observational case-control study will be carried out, with retrospective data analysis. The screening for hereditary thrombophilia will be performed through the Thrombo inCode® panel in cases and controls. The results produced from a single genetic analysis will allow comparison to the centres' routine protocol (FV Leiden and G20210A PT) with the complete Thrombo inCode® panel, that also includes the previously-mentioned classical variants.
- Conditions
- Miscarriage, Recurrent
- Keywords
- Thrombophilia screening, Genetic risk score
- Medical subject headings
- Abortion, Habitual, Genetic Risk Score
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Controls | No intervention | |
| Cases | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrent Pregnancy Loss
Repeated clinical pregnancy loss and/or foetal death (≥ 2 consecutive or ≥ 3 non-consecutive) before the 20th weeks of pregnancy
Measured: 20 weeks
Pregnancy at term
Pregnancy with life-birth
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study startFeb 2015
- Primary completionNov 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Miscarriage, RecurrentStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 364 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferrer inCode, S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinica Universidad de Navarra, Universidad de Navarra, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Instituto Valenciano de Infertilidad, IVI VALENCIA, IVI-RMA London, Instituto de Investigacion Sanitaria La Fe, Gendiag.exe, S.L., Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
- Responsible party
- Sponsor
- Investigators
- Eduardo S Salas, MD, PhD, Study director, Ferrer inCode, S.L.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03336463
- Sponsor's protocol ID
- FerrerinCode
- Acronym
- TiC-RPL
- Status last verified
- Nov 2017
- First submitted
- 23 Oct 2017
- Last updated
- 8 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Soria JM, Morange PE, Vila J, Souto JC, Moyano M, Tregouet DA, Mateo J, Saut N, Salas E, Elosua R. Multilocus genetic risk scores for venous thromboembolism risk assessment. J Am Heart Assoc. 2014 Oct 23;3(5):e001060. doi: 10.1161/JAHA.114.001060.
PubMed 25341889
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score
- ClinicalTrials.gov ID
- NCT03336463
- Acronym / sponsor ID
- TiC-RPL / FerrerinCode
- Conditions
- Miscarriage, Recurrent
- Keywords
- Thrombophilia screening, Genetic risk score
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 364 participants (actual)
- Lead sponsor
- Ferrer inCode, S.L.Industry (pharma, biotech, devices)
- Collaborators
- Clinica Universidad de Navarra, Universidad de Navarra, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Instituto Valenciano de Infertilidad, IVI VALENCIA, IVI-RMA London, Instituto de Investigacion Sanitaria La Fe, Gendiag.exe, S.L., Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
- Study start
- Feb 2015 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 8 Nov 2017 (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 pregnancy loss (RPL) is a clinical problem affecting 1-5% of couples of reproductive age. The contribution of thrombophilia to RPL is disputed. This controversy is partly due to low sensitivity of the genetic variants currently used to evaluate hereditary thrombophilia: the Leiden mutation (identified as rs6025) in the coagulation factor 5 (F5L) gene and mutation G20210A (identified as rs1799963) in the prothrombin (PT) gene.
Our objective was to determine whether a wider algorithm that includes clinic and genetic variants associated with thrombophilia could be more useful in the prediction for RPL than FVL and PT alone.
Detailed description
Recurrent pregnancy loss can affect up to 5% of women in child-bearing age and is considered one of the most common causes of female sterility. In recent years, the association between thrombophilia and pregnancy failure has been observed in a number of studies, varying according to the nature of the thrombophilia (for example the antiphospholipid syndrome as opposed to the hereditary forms) or the type of pregnancy loss (either isolated or recurrent, or early or late). It has therefore been accepted that thrombophilia is detected in a significant number of idiopathic pregnancy losses, reaching 66% of the cases in some series.
Since the 1990's, a number of studies have associated recurrent pregnancy loss with FVL mutations (most frequently) and G20210 PT. In a systematic review, it was confirmed that women with thrombophilia have a higher risk of developing thromboembolism and complications in pregnancy. Another recent meta-analysis of prospective cohort studies concluded that women who were carriers of FVL had a higher risk of late pregnancy loss, at 52%, as opposed to non-carriers (OR=1.52), though the differences in absolute risk were discreet (4.2% and 3.2%, respectively). However, the analysis of these 2 single nucleotide polymorphisms (SNPs) showed low discriminative capacity and diagnostic sensitivity.
This study hypothesize that the use of the Thrombo inCode® in the screening for hereditary thrombophilia in patients with recurrent pregnancy loss can improve the diagnostic sensitivity and predictive capacity of the routine genetic panel, based on FVL and G20210A PT. Thus, the Thrombo inCode® model can accurately identify more patients with clinical-genetic risk of thromboembolism and therefore establish the appropriate preventive measures.
A transversal observational case-control study will be carried out, with retrospective data analysis. The screening for hereditary thrombophilia will be performed through the Thrombo inCode® panel in cases and controls. The results produced from a single genetic analysis will allow comparison to the centres' routine protocol (FV Leiden and G20210A PT) with the complete Thrombo inCode® panel, that also includes the previously-mentioned classical variants.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Controls | – | –No intervention |
| Cases | – | –No intervention |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Age groups
- Adult
- Study population
- The study will include women with recurrent pregnancy loss (> 2 consecutive or > 3 non-consecutive) before the 20th week of pregnancy (cases) and women with at least 1 pregnancy at term (controls).
Key inclusion criteria (7 listed)
- Women >18 and < 38 years old at the time of the first pregnancy.
- Women with successful implantation and at least one full-term pregnancy
- No chronic pathology
- Repeated clinical miscarriages and/or foetal death (≥ 2 consecutive or ≥ 3 non- consecutive) before the 20th weeks of pregnancy, from spontaneous or assisted pregnancies.
- Recurrent miscarriage with the same gametic origin.
Key exclusion criteria (8 listed)
- Personal or family history of thrombosis
- Personal history of obstetric complications Miscarriage or foetal death Pre-eclampsia or eclampsia Intrauterine growth restriction Placental abruption
- Concomitant anticoagulant treatment and/or antiplatelet treatments during pregnancy
- CASES
- Diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Recurrent Pregnancy Loss
Time frame: 20 weeks
Repeated clinical pregnancy loss and/or foetal death (≥ 2 consecutive or ≥ 3 non-consecutive) before the 20th weeks of pregnancy
Pregnancy at term
Time frame: 20 weeks
Pregnancy with life-birth
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 8 Nov 2017.
- Background: PubMed 25341889Soria JM, Morange PE, Vila J, Souto JC, Moyano M, Tregouet DA, Mateo J, Saut N, Salas E, Elosua R. Multilocus genetic risk scores for venous thromboembolism risk assessment. J Am Heart Assoc. 2014 Oct 23;3(5):e001060. doi: 10.1161/JAHA.114.001060.
- Individual participant dataSharing planned: Undecided
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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.
Eduardo S Salas, MD, PhD study director
Ferrer inCode, S.L.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Miscarriage, Recurrent, run by Ferrer inCode, S.L. at 8 sites in 2 countries.
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 7 inclusion and 8 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 8 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Spain, United Kingdom. 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.
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?
Recurrent Pregnancy Loss (time frame: 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03336463, which also lists 1 linked publication.
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 8 Nov 2017.