Recombinant Human Antithrombin (rhAT) in Patients With Hereditary Antithrombin Deficiency Undergoing Surgery or Delivery

Antithrombin III Deficiency Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110513
• Other study ID #: GTC AT HD 012-04
• Status: Completed
• Phase: Phase 3
• First received: May 10, 2005
• Last updated: August 10, 2012
• Start date: April 2005
• Est. completion date: July 2008

Study information

• Verified date: August 2012
• Source: rEVO Biologics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardAustralia: Human Research Ethics CommitteeAustralia: National Health and Medical Research CouncilAustria: EthikkommissionAustria: Federal Ministry for Health and WomenCanada: Ethics Review CommitteeCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeGermany: Ethics CommissionGermany: Paul-Ehrlich-InstitutItaly: Ethics CommitteeItaly: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Antithrombin III Deficiency

Intervention

Biological:
• Recombinant human antithrombin (rhAT)
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
rEVO Biologics

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Venous Thrombosis (DVT)	To assess the incidence of thromboembolic events acute deep venous thrombosis (DVT) and/or thromboembolic events other than acute deep venous thrombosis (DVT) by clinical signs and symptoms of venous thromboembolism (VTE), confirmed by diagnostic assessments.	During treatment and follow up period of 7 days	No