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

NCT ID: NCT00110513

Last Updated: 2012-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2008-07-31

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).

Conditions

Antithrombin III Deficiency

Keywords

Antithrombin Deficiency, Congenital or Hereditary; Antithrombin III Deficiency; ATIII; Hereditary Antithrombin Deficiency (HD)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Recombinant Human Antithrombin (rhAT) Infusion

Intravenous infusion of rhAT.

Group Type: EXPERIMENTAL

Recombinant human antithrombin (rhAT)

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Recombinant human antithrombin (Tradename: ATryn)

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

rEVO Biologics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert C Tait, MD

Role: PRINCIPAL_INVESTIGATOR

Glasgow Royal Infirmary

Locations

New Haven, Connecticut, United States

St Louis, Missouri, United States

New York, New York, United States

North Gosford, , Australia

Vienna, , Austria

Ottawa, Ontario, Canada

Vancouver, , Canada

Montpellier, , France

Berlin, , Germany

Alessandria, , Italy

Exeter, Devon, United Kingdom

Chichester, West Sussex, United Kingdom

Cambridge, , United Kingdom

Glasgow, , United Kingdom

London, , United Kingdom

Nottingham, , United Kingdom

Plymouth, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 24335249 (View on PubMed)

Other Identifiers

GTC AT HD 012-04

Identifier Type: -

Identifier Source: org_study_id