Low Molecular Weight Heparin and/or Aspirin in Prevention of Habitual Abortion

NCT00959621 | Completed Phase 3

• 1 other identifier: HABENOX
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

1 % of all pregnancies end in habitual/recurrent abortion. In about half of women with habitual abortions (HAB) hereditary or acquired (antiphospholipid antibodies) thrombophilia are observed. The investigators wanted to test whether antithrombotic treatment (Low-Molecular Weight Heparin, LMWH, ASA or both combined)would prevent these women from a subsequent abortion. Depending on thrombophilic status the women included in one of the three sub-studies: HABENOX 1 (mild, single thrombophilia), HABENOX 2 (no known thrombophilia), HABENOX 3 (moderate to severe thrombophilia, with combined thrombophilia or moderate to high titer antiphospholipid antibodies). Study design: Randomised placebo controlled multicenter study. Number of patients per study: 90 patients per group, 270 altogether. Timetable: Starting 2/2002, finishing 31.12.2007. Time frame: \>37 weeks of gestation and \>24, but \<37 weeks of gestation (premature) Treatment started before 7. gw. HABENOX 1 and 2: Study groups: Group 1 : Enoxaparin 40 mg+ placebo, Group 2: Enoxaparin 40 +ASA 100 mg, Group 3: ASA. HABENOX 3: Study groups: Group 1: Enoxaparin 40 twice daily+ placebo o.d., Group 2: Enoxaparin 40 mg twice daily +ASA 100 mg o.d. Primary end-points: Pregnancy outcome: livebirths ( ≥37 weeks of gestation), premature livebirths (≥24, but \<37 weeks of gestation) Secondary end-points: Bleeding complications, intrauterine growth retardation (\<-2SD), pre-eclampsia, abruptio placentae, Ending: In the group of combined medication, tablets will be stopped at 36 weeks of gesta-tion. LMWH will be started in all patients after delivery and continued 6 weeks postpartum.

Conditions

Habitual Abortion

Keywords

Habitual abortion; recurrent abortion; hereditary and acquired; thrombophilia; preeclampsia; premature birth; miscarriage; stillbirth; LMWH (low molecular weigh heparin); ASA; aspirin

Outcome Measures

Primary Outcomes (1)

• Pregnancy outcome: livebirths (>37 weeks of gestation), premature livebirths (> 24, but <37 weeks of gestation)

  gestational weeks >37 and gestational weeks > 24, but <37

Secondary Outcomes (1)

• Bleeding complications, intrauterine growth retardation (<-2SD), pre-eclampsia, abruption placenta

  gestational weeks > 37 and gestational weeks >24, but <37

Study Arms (3)

ASA

ACTIVE COMPARATOR

The patients received either Enoxaparine+placebo, Enoxaparine+ASA (Aspirin 100 mg) or ASA alone.ASA or placebo were blinded in the two first groups.

Drug: Aspirin

Klexane

ACTIVE COMPARATOR

Clexane (enoxaparine) 40 mg sc

Drug: Klexane

Aspirin and Enoxaparine

ACTIVE COMPARATOR

Drug: Klexane and ASA

Interventions

Aspirin DRUG

ASA 100 mg once daily per os

ASA

Klexane DRUG

Klexane 40 mg sc once daily (HABENOX 1 and 2), Klexane 40 mg twice daily in HABENOX 3

Klexane

Klexane and ASA DRUG

Klexane 40 mgx 1 sc and ASA 100 mg po

Aspirin and Enoxaparine

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Habenox 1: Three or more consecutive abortions of first trimester (ad h 12+6 wks) or two second trimester abortions (ad h 13 wks-23+6 wks) or one third trimester abortion (24 weeks or more) with one first-second trimester abortions and one thrombophiliatest positive: F V Leiden (heterozygote) or protein C or S deficiency, or anticardiolipin antibodies (low to moderate level), prothrombin gene mutation, or high level of F VIII.
• HABENOX 2: The thrombophilic tests above are negative.
• HABENOX 3:positive combined thrombophilia, F V Leiden (homozygote), anticardiolipin antibodies (high level \>40) , lupusanticoagulant, or AT III deficiency.

You may not qualify if:

• History of DVT or pulmonary embolism.
• Significant bleeding history.

Sponsors & Collaborators

• University of Helsinki: lead
• Oulu University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Leiden Hospital, Leiden, The Netherlands: collaborator

Study Sites (1)

Helsinki University Hospital

Helsinki, 00290, Finland

Location

Related Publications (1)

• 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.

  PMID: 32358837 DERIVED

MeSH Terms

Conditions

Abortion, Habitual; Thrombophilia; Pre-Eclampsia; Premature Birth; Abortion, Spontaneous; Stillbirth

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypertension, Pregnancy-Induced; Obstetric Labor, Premature; Obstetric Labor Complications; Fetal Death; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Veli-Matti Ulander, MD

  Helsinki University Hospital, Finland

  PRINCIPAL INVESTIGATOR

• Laure Morin-Papunen, MD

  Oulu University Hospital

  STUDY CHAIR

• Katja Lampinen, MD

  Karolinska University Hospital

  STUDY CHAIR

• Kitty Bloemenkamp, MD

  Leiden University Hospital, Leiden, The Netherlands

  STUDY CHAIR

• Janvier Visser, MD

  Leiden University Hospital, Leiden, The Netherlands

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 21, 2009
• First Posted: August 14, 2009
• Study Start: January 1, 2002
• Primary Completion: December 1, 2004
• Study Completion: December 1, 2008
• Last Updated: August 14, 2009

Record last verified: 2009-08

Locations

FI (1)