Recombinant Human Antithrombin (rhAT) in Patients With Hereditary Antithrombin Deficiency Undergoing Surgery or Delivery
Condition: Antithrombin III Deficiency
MeSH terms: Antithrombin III Deficiency
Intervention: Recombinant human antithrombin (rhAT)
Intervention description: Up to 24 hours prior to the scheduled elective surgical procedure, caesarean section, or delivery induction, each patient will receive an initial intravenous loading dose followed by a continuous intravenous infusion of recombinant human antithrombin (rhAT) that will target and maintain an AT activity that is > 80% and < 120% of normal. The dosing objective for all study patients is maintenance of the AT activity at > 80% and < 120% of normal during the high-risk period for thromboembolic events. Dosing and dose adjustments will be based on the results of AT activity determinations performed prior to and during treatment.
Intervention MeSH terms: Antithrombins; Antithrombin III
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Antithrombin Deficiency, Congenital or Hereditary; Antithrombin III Deficiency; ATIII; Hereditary Antithrombin Deficiency (HD)

Summary:

      Patients with hereditary antithrombin deficiency are at increased risk of venous thrombosis
      and pulmonary embolism, particularly during certain high risk procedures. The trial focused
      on patients with confirmed hereditary antithrombin deficiency who were undergoing a surgical
      procedure or induced/spontaneous labor and delivery, and/or caesarean section. The study
      assessed the incidence of thromboembolic events following prophylactic intravenous
      administration of recombinant human antithrombin (rhAT) to patients with hereditary
      antithrombin (AT) deficiency in situations usually associated with a high risk for
      thromboembolic events.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have hereditary antithrombin deficiency (HD) with a personal history of venous
             thromboembolic events.

          2. Have a history of HD that includes 2 or more plasma AT activity values ≤ 60%.

          3. Be scheduled to have an elective procedure(s) known to be associated with a high risk
             for occurrence for DVT. This will include non-pregnant surgical patients or pregnant
             patients scheduled for caesarean section or delivery induction.

          4. Be at least 18 years of age, not exceeding 80 years of age.

          5. Have signed an informed consent form.

          6. Have a negative serum pregnancy test at screening and a negative urine pregnancy test
             at baseline. This applies only to female non-pregnant surgical patients of
             childbearing potential.

          7. Are able to comply with the requirements of the study protocol.

        In addition, hospitalized pregnant HD patients in active labor and eligible HD patients
        previously treated with rhAT were allowed entry into the study.

        Exclusion Criteria:

          1. Patients who have a diagnosis of another hereditary thrombophilic disorder (e.g.
             activated protein C(APC) resistance/Factor V Leiden, Protein S or C deficiency,
             prothrombin gene mutation (G20210A), or acquired (lupus anticoagulant) thrombophilic
             disorder).

          2. Patients who have a baseline bilateral ultrasound positive for acute DVT or baseline
             diagnostic testing (if required) that is positive for a thromboembolic event other
             than acute DVT.

          3. Patients who have a known allergy to goats or goat products.

          4. Patients who have participated in a study employing a different investigational drug
             within 30 days of the start of their participation in the current trial.

          5. Patients using fondaparinux sodium or the oral thrombin inhibitor, ximelagatran, or
             are expected to be treated with fondaparinux sodium or ximelagatran during the study
             period (up to 7 days after stop of treatment).