InfertilityPhase 3NCT02991950
Weight Adjusted Low Molecular Weight Heparin in Recurrent Implantation Failure: a Randomized Open Labeled Trial
A Phase 3 study testing Parnaparin Sodium in people with Infertility and Low Molecular Weight Heparin, run by Istituto Clinico Humanitas.
Trial summary
Prospective randomized study of patients with infertility candidates to Assisted ReproductiveTechniques (ART), screened for all inclusion and exclusion criteria, submitted to ART cycle with or without low molecular weight heparin (LMWH) administration. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility, Low Molecular Weight Heparin
- What is being tested?
- Parnaparin Sodium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 271 participants
- Where
- No sites listed yet
- Study dates
- Jul 2011to Dec 2015
- Phase
- Phase 3
- 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 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women ≥18 years and ≤40 years, candidated to a fresh IVF/ICSI cycle with routine ovulation induction protocol
Who cannot join
- v-vCouples candidated to a frozen IVF/ICSI cycle with routine ovulation induction protocol
- Testicular or frozen sperm (TESE procedure not allowed)
- Presence of hormonal disorders not compensated with specific therapy or history of immunological disease (autoimmune thyroiditis, connectivitis, RA, SLE, etc )
- Presence of antiphospholipides autoantibodies or other severe thrombophilia (AT, PS, PC deficiency or homozygous FV Leiden or FIIG20210A, or double eterozygous FV Leiden and FIIG20210A)
- Presence of abnormal platelets count and congenital or acquired coagulopathy ASA or steroid therapy administration
About this study
Prospective randomized study of patients with infertility candidates to Assisted ReproductiveTechniques (ART), screened for all inclusion and exclusion criteria, submitted to ART cycle with or without low molecular weight heparin (LMWH) administration. Aims of the study are to evaluate, primarily, pregnancy rate/embryo transfer, secondarily take home babies/embryo transfer, implantation rate, and the role of thrombophilic factors
Read the detailed description
This is an interventional, stratified, randomized, open blind study. It will conducted on outpatients selected on the basis of inclusion and exclusion criteria.
Patients will be randomised according to a computer generated list of randomization to receive or not LMWH at prophylactic daily dosage (100 IU/kg).
For a correct selection and analysis some parameters have to be checked before randomization (see randomization check list at the end). The women in LMWH arm will treated starting the day before the beginning of stimulation phase of the cycle of ART until the result of the procedure is confirmed in terms of pregnancy yes or no, and if the pregnancy will be confirmed until the delivery or the end of pregnancy. Women in the control arm are administered routine hormonal support without LMWH.
Data will be collected on smoking habits, BMI, the number of retrieved oocytes, transferred embryos and implantation rate, ART outcome and parameters used for randomization on the basis of inclusion and exclusion criteria.
During the study blood will be collected for analysis at the randomization, the moment in wich patient will be assigned to one of the two arms, at the transfer and at the day of check for betaHCG and in in case of pregnancy all women will be checked at 12, 24, 36 week for testing of functional parameters of coagulation (protein C, protein S, AT, ddimer, fibrinogen, PT, aPTT, FVII, FVIII, FIX, and vonWillebrand factor antigen), blood cells count and of lipids (cholesterol and triglycerides).
The samples, identified with a sequential identification number, will be collected, processed and storage at -20/-80°C in the promoter center and will be destroyed after the analyses.
Study treatment Women in LMWH arm are administered with prophylactic weight adjusted dose of LMWH, starting the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until the delivery or the end of pregnancy. Women in the LMWH arm will be tested for blood cell count twice in the first 10 days of therapy.
Initial dose and schedule Parnaparin will be administered at the dose of 100 IU/kg/day from the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until delivery or the end of the pregnancy.
None of patients can receive concomitant acetylsalicylic acid (ASA) or steroids therapy Treatment duration
Women in LMWH arm are administered with prophylactic weight adjusted dose of parnaparin, starting the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until the delivery or the end of the pregnancy.
Whatever the disease status, the treatment will always be discontinued in case of patient refusal excessive toxicity precluding further therapy, according to the responsible physicianother complications, according to the responsible physician
- Conditions
- Infertility, Low Molecular Weight Heparin
- Being tested
- Parnaparin Sodium
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parnaparin SodiumDrug
Also called Fluxum
Parnaparin sodium ( Fluxum 4250 anti-Xa IU /0.4 mL or Fluxum 6400 anti-Xa IU /0.6mL; Alfa Wassermann S.p.A.) was administered at a dose of 100 IU/kg/day from the day before the beginning of the stimulation phase of the cycle until the result of the procedure was confirmed by pregnancy and, in the case of evolutive pregnancy, until delivery or the end of pregnancy
| Study group | Role | What they receive |
|---|---|---|
| parnaparin sodium | Experimental | Women in LMWH arm are administered with routine ovulation induction protocol and prophylactic dose of parnaparin sodium (LMWH), starting the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until the delivery or the end of pregnancy. Women in the LMWH arm will be tested for blood cell count twice in the first 10 days of therapy.
Parnaparin will be administered at the dose of 100 IU/kg/day from the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until delivery or the end of the pregnancy.
Used dosages Parnaparin 0.4 4250 UI Parnaparin 0.6 6400 UI Receives: Drug: Parnaparin Sodium |
| no treatment | No intervention | Women in the control arm are administered with routine ovulation induction protocol, without the addition of parnaparin sodium. |
What is being measured
The primary outcome is the main question the study is designed to answer.
pregnancy rate/embryo transfer
the investigators measured the pregnancy rate/embryo transfer using betaHcg dosage 12 days after embryo transfer
Measured: 12-14 days
Secondary outcomes (3)
take home babies/embryo transfer
Live birth was defined as delivery of one or more live infants after 23 gestational weeks.
Measured: 38-40 weeks after embryo transfer
implantation rate
ultrasound was performed to evaluate implantation rate calculated as as number of gestational sacs divided by number of transferred embryos multiplied by 100
Measured: 3 weeks
role of thrombophilia in interfering with pregnancy rate/take home baby/implantation rate
All enrolled patients were previously screened for the presence or not of thrombophilic defects: protein C or protein S or AT deficiency, FV G1691A and FIIG20210A mutations, C677T MTHFR polymorphism,hyperhomocysteinemia, antiphospholipid antibodies. The investigators excluded from the enrollment patients with severe thrombophilia: protein C, protein S, AT deficiency or homozygous FV Leiden and FIIG20210A mutations or double heterozygosity for FV Leiden and FIIG20120 mutations because in this patients the international guide lines suggest and recommend the use of antithrombotic prophylaxis
Measured: 12-14 days and 38-40 weeks and 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study startJul 2011
- Primary completionMar 2015
- Study completionDec 2015
Why it stopped: Difficulty with patient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 271 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- corrado lodigiani, MD,PHD, Principal investigator, Thrombosis Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02991950
- Sponsor's protocol ID
- 876
- Status last verified
- Dec 2016
- First submitted
- 29 Nov 2016
- Last updated
- 14 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Weight Adjusted Low Molecular Weight Heparin in Recurrent Implantation Failure: a Randomized Open Labeled Trial
- ClinicalTrials.gov ID
- NCT02991950
- Acronym / sponsor ID
- 876
- Conditions
- Infertility, Low Molecular Weight Heparin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty with patient enrollment
- Enrolment
- 271 participants (actual)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 14 Dec 2016 (estimated)
- 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.
Prospective randomized study of patients with infertility candidates to Assisted ReproductiveTechniques (ART), screened for all inclusion and exclusion criteria, submitted to ART cycle with or without low molecular weight heparin (LMWH) administration. Aims of the study are to evaluate, primarily, pregnancy rate/embryo transfer, secondarily take home babies/embryo transfer, implantation rate, and the role of thrombophilic factors
Detailed description
This is an interventional, stratified, randomized, open blind study. It will conducted on outpatients selected on the basis of inclusion and exclusion criteria.
Patients will be randomised according to a computer generated list of randomization to receive or not LMWH at prophylactic daily dosage (100 IU/kg).
For a correct selection and analysis some parameters have to be checked before randomization (see randomization check list at the end). The women in LMWH arm will treated starting the day before the beginning of stimulation phase of the cycle of ART until the result of the procedure is confirmed in terms of pregnancy yes or no, and if the pregnancy will be confirmed until the delivery or the end of pregnancy. Women in the control arm are administered routine hormonal support without LMWH.
Data will be collected on smoking habits, BMI, the number of retrieved oocytes, transferred embryos and implantation rate, ART outcome and parameters used for randomization on the basis of inclusion and exclusion criteria.
During the study blood will be collected for analysis at the randomization, the moment in wich patient will be assigned to one of the two arms, at the transfer and at the day of check for betaHCG and in in case of pregnancy all women will be checked at 12, 24, 36 week for testing of functional parameters of coagulation (protein C, protein S, AT, ddimer, fibrinogen, PT, aPTT, FVII, FVIII, FIX, and vonWillebrand factor antigen), blood cells count and of lipids (cholesterol and triglycerides).
The samples, identified with a sequential identification number, will be collected, processed and storage at -20/-80°C in the promoter center and will be destroyed after the analyses.
Study treatment Women in LMWH arm are administered with prophylactic weight adjusted dose of LMWH, starting the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until the delivery or the end of pregnancy. Women in the LMWH arm will be tested for blood cell count twice in the first 10 days of therapy.
Initial dose and schedule Parnaparin will be administered at the dose of 100 IU/kg/day from the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until delivery or the end of the pregnancy.
None of patients can receive concomitant acetylsalicylic acid (ASA) or steroids therapy Treatment duration
Women in LMWH arm are administered with prophylactic weight adjusted dose of parnaparin, starting the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until the delivery or the end of the pregnancy.
Whatever the disease status, the treatment will always be discontinued in case of patient refusal excessive toxicity precluding further therapy, according to the responsible physicianother complications, according to the responsible physician
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| parnaparin sodium | Experimental | Drug: Parnaparin SodiumWomen in LMWH arm are administered with routine ovulation induction protocol and prophylactic dose of parnaparin sodium (LMWH), starting the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until the delivery or the end of pregnancy. Women in the LMWH arm will be tested for blood cell count twice in the first 10 days of therapy. Parnaparin will be administered at the dose of 100 IU/kg/day from the day before the beginning of stimulation phase of the cycle until the result of the procedure is confirmed in terms of pregnancy yes or no and in case of pregnancy until delivery or the end of the pregnancy. Used dosages Parnaparin 0.4 4250 UI Parnaparin 0.6 6400 UI |
| no treatment | No intervention | –Women in the control arm are administered with routine ovulation induction protocol, without the addition of parnaparin sodium. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Women ≥18 years and ≤40 years, candidated to a fresh IVF/ICSI cycle with routine ovulation induction protocol
Key exclusion criteria (5 listed)
- v-vCouples candidated to a frozen IVF/ICSI cycle with routine ovulation induction protocol
- Testicular or frozen sperm (TESE procedure not allowed)
- Presence of hormonal disorders not compensated with specific therapy or history of immunological disease (autoimmune thyroiditis, connectivitis, RA, SLE, etc )
- Presence of antiphospholipides autoantibodies or other severe thrombophilia (AT, PS, PC deficiency or homozygous FV Leiden or FIIG20210A, or double eterozygous FV Leiden and FIIG20210A)
- Presence of abnormal platelets count and congenital or acquired coagulopathy ASA or steroid therapy administration
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 |
|---|---|---|
| Parnaparin SodiumAlso: FluxumParnaparin sodium ( Fluxum 4250 anti-Xa IU /0.4 mL or Fluxum 6400 anti-Xa IU /0.6mL; Alfa Wassermann S.p.A.) was administered at a dose of 100 IU/kg/day from the day before the beginning of the stimulation phase of the cycle until the result of the procedure was confirmed by pregnancy and, in the case of evolutive pregnancy, until delivery or the end of pregnancy | Drug | parnaparin sodium |
Primary outcome
pregnancy rate/embryo transfer
Time frame: 12-14 days
the investigators measured the pregnancy rate/embryo transfer using betaHcg dosage 12 days after embryo transfer
3 secondary outcomes
take home babies/embryo transfer
Time frame: 38-40 weeks after embryo transfer
implantation rate
Time frame: 3 weeks
role of thrombophilia in interfering with pregnancy rate/take home baby/implantation rate
Time frame: 12-14 days and 38-40 weeks and 3 weeks
Results and safety
The study was stopped early (reason given: Difficulty with patient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2016.
- Individual participant dataSharing planned: No
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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.
corrado lodigiani, MD,PHD principal investigator
Thrombosis Center
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Parnaparin Sodium in people with Infertility and Low Molecular Weight Heparin, run by Istituto Clinico Humanitas.
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 1 inclusion and 5 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: stopped early, as of the sponsor's last update on 14 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Difficulty with patient enrollment). Results are not available in the source record.
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?
pregnancy rate/embryo transfer (time frame: 12-14 days). 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 14 Dec 2016.