Clinical trial NCT00110513: Recombinant Human Antithrombin (rhAT) in Patients With Hereditary Antithrombin Deficiency Undergoing Surgery or Delivery
Official title: A Multicenter, Multinational Study to Assess the Safety and Efficacy of Antithrombin Alfa in Hereditary Antithrombin (AT) Deficient Patients in High-Risk Situations for Thrombosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Antithrombin III Deficiency
Keywords: Antithrombin Deficiency, Congenital or Hereditary
Antithrombin III Deficiency
ATIII
Hereditary Antithrombin Deficiency (HD)
Lead sponsor: rEVO Biologics
Sponsor class: INDUSTRY
First posted: 2005-05-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Detailed description: GTC Biotherapeutics established clinical trial sites in Europe, Canada, Australia, Austria and Canada. GTC Biotherapeutics provided an international clinical team to support site registration requirements once a patient was identified for treatment. GTC Biotherapeutics also provided consultation to help evaluate patient eligibility.

In September 2006, GTC Biotherapeutics modified exclusion criteria 1 (below) to allow for the participation of previously excluded patients with the hereditary thrombophilic disorders Factor V Leiden and prothrombin gene mutation (G20210A).

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).

Primary outcomes:
measure: Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Venous Thrombosis (DVT)
timeFrame: During treatment and follow up period of 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
state: Connecticut
city: St Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: North Gosford
country: Australia
city: Vienna
country: Austria
city: Ottawa
country: Canada
state: Ontario
city: Vancouver
country: Canada
city: Montpellier
country: France
city: Berlin
country: Germany
city: Alessandria
country: Italy
city: Exeter
country: United Kingdom
state: Devon
city: Chichester
country: United Kingdom
state: West Sussex
city: Cambridge
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
Study officials:
affiliation: Glasgow Royal Infirmary
name: Robert C Tait, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: DeJongh J, Frieling J, Lowry S, Drenth HJ. Pharmacokinetics of recombinant human antithrombin in delivery and surgery patients with hereditary antithrombin deficiency. Clin Appl Thromb Hemost. 2014 May;20(4):355-64. doi: 10.1177/1076029613516188. Epub 2013 Dec 11.