Preconceptional Thromboprophylaxis in Recurrent PREGNANCY LOSSES Caused by Antiphospholipid Syndrome

A Randomized Clinical Trial of Using Preconceptional Enoxaparin AND Low Dose Aspirin 81mg in Patient With Antiphospholipid Syndrome(APS)

Preconceptional use of low molecular weight heparin (enoxaparin) and aspirin in patient with recurrent miscarriages with positive anti phospholipid antibodies increase the implantation rate and the duration of pregnancy with low complications to the mother and the baby.

Study Overview

• Status: Unknown
• Conditions: Recurrent Pregnancy Losses; Positive Anti Phospholipid Syndrome
• Intervention / Treatment: Drug: low molecular weight heparin (enoxeparine)

Detailed Description

Preconceptional heparin during follicular or luteal phase,improves the implantation rate by increasing the blood flow and increasing the implantation factors,also decreasing the pregnancy complication resulting from Antiphospholipid Syndrome (APS).

• Study Type: Observational
• Enrollment (Anticipated): 316

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Recruiting
    • Women Health Hospital
    • Contact: HASSAN S KAMEL, MD; Phone Number: +2010066436; Email: hkamelhkamel@yahoo.com
    • Principal Investigator: Alaa M Ismail, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

patients with recurrent pregnancy losses either two or more recurrent miscarriages or intrauterine fetal deathes after 20 weeks of gestation with positive antiphospholipid antibodies in medium to high titer in two occasions 6 weeks apart.

Description

Inclusion Criteria:

1. All women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriage who screened before pregnancy for antiphospholipid antibodies.
2. To diagnose antiphospholipid syndrome it is mandatory that the woman has two positive tests at least 12 weeks apart for either lupus anticoagulant or anticardiolipin antibodies of immunoglobulin G and/or immunoglobulin M class present in a medium or high titre over 40 g/l or ml/l,or above the 99th percentile).

In the detection of lupus anticoagulant, the dilute Russell's viper venom time test together with a platelet neutralisation procedure is more sensitive and specific than either the activated partial thromboplastin time test or the kaolin clotting time test. Anticardiolipin antibodies are detected using a standardised enzyme linked immunosorbent assay.

Exclusion Criteria:

1. Age above forty years old .
2. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram, or hysteroscopy).
3. Fibroids distorting uterine cavity .
4. Abnormal parental karyotype .
5. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated) e.g., diabetes, thyroid disease and systemic lupus erythematosus (SLE).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low molecular weight heparin; SC LMWH IN patients with recurrent pregnancy loss	Drug: low molecular weight heparin (enoxeparine); 1mg/kg enoxeparine SC daily from 1st day of the menstrual cycle and continue daily throughout the pregnancy after documentation of pregnancy,and stopped in absence of fetal cardiac activity.; Other Names: clexane,innohep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy continuation beyond twelve weeks gestation	giving low molecular weight heparin (enoxaparin) and 81 mg aspirin in patients with positive anti phospholipid antibodies with history of recurrent miscarriages or intrauterine fetal deaths in the preconceptional period one month before pregnancy with follow up as regarding the clinical pregnancy rate,the rate of continuation of pregnancy beyond 28 weeks gestation and the complications related to long term use of heparin and the severity of complication of APS in comparison to the traditional use of anticoagulant after documentation of the fetal heart rate	ONE YEAR

Collaborators and Investigators

• Sponsor: Woman's Health University Hospital, Egypt

Publications and helpful links

General Publications

• Hamulyak EN, Scheres LJ, Marijnen MC, Goddijn M, Middeldorp S. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev. 2020 May 2;5(5):CD012852. doi: 10.1002/14651858.CD012852.pub2.
• Ismail AM, Hamed AH, Saso S, Abu-Elhasan AM, Abu-Elghar MM, Abdelmeged AN. Randomized controlled study of pre-conception thromboprophylaxis among patients with recurrent spontaneous abortion related to antiphospholipid syndrome. Int J Gynaecol Obstet. 2016 Feb;132(2):219-23. doi: 10.1016/j.ijgo.2015.09.004. Epub 2015 Dec 2.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): June 1, 2014

Study Registration Dates

• First Submitted: July 25, 2012
• First Submitted That Met QC Criteria: August 8, 2012
• First Posted (Estimate): August 9, 2012

Study Record Updates

• Last Update Posted (Estimate): June 23, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Recurrent miscarriages; recurrent pregnancy loss; aps; anti coagulants in pregnancy
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease Attributes; Disease; Pregnancy Complications; Death; Syndrome; Recurrence; Abortion, Spontaneous; Abortion, Habitual; Antiphospholipid Syndrome; Fetal Death; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: PCTRPL; preconceptional heparin in APS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No