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

This study has been completed.
Sponsor:
Collaborators:
Oulu University Hospital, Oulu, Finland
Karolinska Hospital, Stockholm, Sweden
Leiden Hospital, Leiden, The Netherlands
Information provided by:
Helsinki University
ClinicalTrials.gov Identifier:
NCT00959621
First received: July 21, 2009
Last updated: August 13, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Habitual Abortion
Drug: Aspirin
Drug: Klexane
Drug: Klexane and ASA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Role of LMWH (Enoxaparine) With or Without Aspirin in the Prevention of Habitual Abortion; Special Attention to the Thrombophilic Status of the Mother

Resource links provided by NLM:


Further study details as provided by Helsinki University:

Primary Outcome Measures:
  • Pregnancy outcome: livebirths (>37 weeks of gestation), premature livebirths (> 24, but <37 weeks of gestation) [ Time Frame: gestational weeks >37 and gestational weeks > 24, but <37 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Bleeding complications, intrauterine growth retardation (<-2SD), pre-eclampsia, abruption placenta [ Time Frame: gestational weeks > 37 and gestational weeks >24, but <37 ] [ Designated as safety issue: Yes ]

Enrollment: 220
Study Start Date: January 2002
Study Completion Date: December 2008
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ASA
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
ASA 100 mg once daily per os
Active Comparator: Klexane
Clexane (enoxaparine) 40 mg sc
Drug: Klexane
Klexane 40 mg sc once daily (HABENOX 1 and 2), Klexane 40 mg twice daily in HABENOX 3
Active Comparator: Aspirin and Enoxaparine Drug: Klexane and ASA
Klexane 40 mgx 1 sc and ASA 100 mg po

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • History of DVT or pulmonary embolism.
  • Significant bleeding history.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00959621

Locations
Finland
Helsinki University Hospital
Helsinki, Finland, 00290
Sponsors and Collaborators
Helsinki University
Oulu University Hospital, Oulu, Finland
Karolinska Hospital, Stockholm, Sweden
Leiden Hospital, Leiden, The Netherlands
Investigators
Principal Investigator: Veli-Matti Ulander, MD Helsinki University Hospital, Finland
Study Chair: Laure Morin-Papunen, MD Oulu University Hospital, Oulu, Finland
Study Chair: Katja Lampinen, MD Karolinska Hospital, Stockholm, Sweden
Study Chair: Kitty Bloemenkamp, MD Leiden University Hospital, Leiden, The Netherlands
Study Chair: Janvier Visser, MD Leiden University Hospital, Leiden, The Netherlands
  More Information

No publications provided

Responsible Party: Professor Risto Kaaja, Helsinki University Hospital
ClinicalTrials.gov Identifier: NCT00959621     History of Changes
Other Study ID Numbers: HABENOX
Study First Received: July 21, 2009
Last Updated: August 13, 2009
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Helsinki University:
Habitual abortion
recurrent abortion
hereditary and acquired
thrombophilia
preeclampsia
premature birth
miscarriage
stillbirth
LMWH (low molecular weigh heparin)
ASA
aspirin

Additional relevant MeSH terms:
Abortion, Habitual
Abortion, Spontaneous
Pregnancy Complications
Aspirin
Heparin, Low-Molecular-Weight
Dalteparin
Enoxaparin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Anticoagulants

ClinicalTrials.gov processed this record on August 27, 2014