Weight Adjusted Low Molecular Weight Heparin in Recurrent Implantation Failure: a Randomized Open Labeled Trial

NCT ID: NCT02991950

Last Updated: 2016-12-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 271 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2015-12-31

Brief 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. 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

Conditions

Infertility; Low Molecular Weight Heparin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

parnaparin sodium

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

Group Type: EXPERIMENTAL

Parnaparin Sodium

Intervention Type: DRUG

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

no treatment

Women in the control arm are administered with routine ovulation induction protocol, without the addition of parnaparin sodium.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Parnaparin Sodium

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

Intervention Type: DRUG

Other Intervention Names

Fluxum

Eligibility Criteria

Inclusion Criteria

• Women ≥18 years and ≤40 years, candidated to a fresh IVF/ICSI cycle with routine ovulation induction protocol

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Istituto Clinico Humanitas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

corrado lodigiani, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

Thrombosis Center

Other Identifiers

876

Identifier Type: -

Identifier Source: org_study_id