Recombinant Human Antithrombin (rhAT) in Patients With Hereditary Antithrombin Deficiency Undergoing Surgery or Delivery
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Recombinant Human Antithrombin (rhAT) Infusion Intravenous infusion of rhAT. |
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Venous Thrombosis (DVT) [During treatment and follow up period of 7 days]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have hereditary antithrombin deficiency (HD) with a personal history of venous thromboembolic events.
-
Have a history of HD that includes 2 or more plasma AT activity values ≤ 60%.
-
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.
-
Be at least 18 years of age, not exceeding 80 years of age.
-
Have signed an informed consent form.
-
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.
-
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:
-
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).
-
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.
-
Patients who have a known allergy to goats or goat products.
-
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.
-
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New Haven | Connecticut | United States | ||
| 2 | St Louis | Missouri | United States | ||
| 3 | New York | New York | United States | ||
| 4 | North Gosford | Australia | |||
| 5 | Vienna | Austria | |||
| 6 | Ottawa | Ontario | Canada | ||
| 7 | Vancouver | Canada | |||
| 8 | Montpellier | France | |||
| 9 | Berlin | Germany | |||
| 10 | Alessandria | Italy | |||
| 11 | Exeter | Devon | United Kingdom | ||
| 12 | Chichester | West Sussex | United Kingdom | ||
| 13 | Cambridge | United Kingdom | |||
| 14 | Glasgow | United Kingdom | |||
| 15 | London | United Kingdom | |||
| 16 | Nottingham | United Kingdom | |||
| 17 | Plymouth | United Kingdom |
Sponsors and Collaborators
- rEVO Biologics
Investigators
- Principal Investigator: Robert C Tait, MD, Glasgow Royal Infirmary
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GTC AT HD 012-04
Study Results
Participant Flow
| Recruitment Details | The study population included non pregnant patients who were scheduled for surgery and pregnant patients who were scheduled for caesarean section or delivery induction or were hospitalized in active labor. |
|---|---|
| Pre-assignment Detail | Eighteen patients were treated with recombinant human antithrombin (rhAT) and analyzed for safety. |
| Arm/Group Title | Recombinant Human Antithrombin (rhAT) Infusion |
|---|---|
| Arm/Group Description | Up to 24 hours prior to the scheduled elective surgical procedure, caesarean section, or delivery induction, each patient received an initial intravenous loading dose of recombinant human antithrombin (rhAT)followed by a continuous intravenous infusion dose of recombinant human antithrombin (rhAT) to maintain an antithrombin (AT) activity level of >80% and <120% of normal. |
| Period Title: Overall Study | |
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Recombinant Human Antithrombin (rhAT) Infusion |
|---|---|
| Arm/Group Description | Up to 24 hours prior to the scheduled elective surgical procedure, caesarean section, or delivery induction, each patient received an initial intravenous loading dose of recombinant human antithrombin (rhAT)followed by a continuous intravenous infusion dose of recombinant human antithrombin (rhAT) to maintain an antithrombin (AT) activity level of >80% and <120% of normal. |
| Overall Participants | 18 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
18
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
37.2
(12.2)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
14
77.8%
|
| Male |
4
22.2%
|
| Region of Enrollment (participants) [Number] | |
| France |
3
16.7%
|
| Canada |
2
11.1%
|
| Australia |
1
5.6%
|
| Germany |
1
5.6%
|
| United Kingdom |
8
44.4%
|
| Italy |
1
5.6%
|
| United States |
2
11.1%
|
| Prior history of thromboembolism (Number) [Number] | |
| Number [Participants] |
18
100%
|
| Antithrombin (AT) activity level <60% (Number) [Number] | |
| Number [Participants] |
18
100%
|
Outcome Measures
| Title | Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Venous Thrombosis (DVT) |
|---|---|
| Description | 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. |
| Time Frame | During treatment and follow up period of 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population |
| Arm/Group Title | Recombinant Human Antithrombin (rhAT) Infusion |
|---|---|
| Arm/Group Description | Up to 24 hours prior to the scheduled elective surgical procedure, caesarean section, or delivery induction, each patient received an initial intravenous loading dose of recombinant human antithrombin (rhAT)followed by a continuous intravenous infusion dose of recombinant human antithrombin (rhAT) to maintain an antithrombin (AT) activity level >80% and <120% of normal. |
| Measure Participants | 18 |
| Number [Participants] |
0
0%
|
Adverse Events
| Time Frame | Until 28 days after end of treatment. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Recombinant Human Antithrombin (rhAT) Infusion | |
| Arm/Group Description | Up to 24 hours prior to the scheduled elective surgical procedure, caesarean section, or delivery induction, each patient received an initial intravenous loading dose of recombinant human antithrombin (rhAT)followed by a continuous intravenous infusion dose of recombinant human antithrombin (rhAT) to maintain an antithrombin (AT) activity level of >80% and <120% of normal. | |
All Cause Mortality |
||
| Recombinant Human Antithrombin (rhAT) Infusion | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Recombinant Human Antithrombin (rhAT) Infusion | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/18 (27.8%) | |
| Gastrointestinal disorders | ||
| Intra-Abdominal | 1/18 (5.6%) | 1 |
| Infections and infestations | ||
| Enterobacter Sepsis | 1/18 (5.6%) | 1 |
| Investigations | ||
| Hemoglobin decreased | 1/18 (5.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Haemarthrosis | 1/18 (5.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pulmonary Embolism | 1/18 (5.6%) | 1 |
| Vascular disorders | ||
| Haematoma | 1/18 (5.6%) | 1 |
| DVT | 1/18 (5.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Recombinant Human Antithrombin (rhAT) Infusion | ||
| Affected / at Risk (%) | # Events | |
| Total | 16/18 (88.9%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 3/18 (16.7%) | 3 |
| Cardiac disorders | ||
| Tachycardia | 1/18 (5.6%) | 1 |
| Eye disorders | ||
| Vision Blurred | 1/18 (5.6%) | 1 |
| Gastrointestinal disorders | ||
| Vomiting | 3/18 (16.7%) | 3 |
| Abdominal Distention | 1/18 (5.6%) | 1 |
| Abdominal Pain | 1/18 (5.6%) | 1 |
| Constipation | 1/18 (5.6%) | 1 |
| Dental Discomfort | 1/18 (5.6%) | 1 |
| Dyspepsia | 1/18 (5.6%) | 1 |
| Flatulence | 1/18 (5.6%) | 1 |
| Haemorrhoids | 1/18 (5.6%) | 1 |
| Injection Site Bruising | 1/18 (5.6%) | 1 |
| General disorders | ||
| Non-Cardiac Chest Pain | 2/18 (11.1%) | 2 |
| Oedema Peripheral | 2/18 (11.1%) | 2 |
| Feeling Hot | 1/18 (5.6%) | 1 |
| Infections and infestations | ||
| Urinary Tract Infection | 2/18 (11.1%) | 2 |
| Gastroenteritis Viral | 1/18 (5.6%) | 1 |
| Wound Infection | 1/18 (5.6%) | 1 |
| Injury, poisoning and procedural complications | ||
| Post Procedural Hemmorhage | 2/18 (11.1%) | 2 |
| Incision Site Complication | 1/18 (5.6%) | 1 |
| Procedural Pain | 1/18 (5.6%) | 1 |
| Vascular Graft Occlusion | 1/18 (5.6%) | 1 |
| Wound Complicaton | 1/18 (5.6%) | 1 |
| Investigations | ||
| C-Reactive Protein Increased | 1/18 (5.6%) | 1 |
| Hepatic Enzyme Abnormal | 1/18 (5.6%) | 1 |
| Metabolism and nutrition disorders | ||
| Hypokalemia | 1/18 (5.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Arthropathy | 1/18 (5.6%) | 1 |
| Muscle Spasms | 1/18 (5.6%) | 1 |
| Nervous system disorders | ||
| Headache | 2/18 (11.1%) | 5 |
| Syncope | 2/18 (11.1%) | 2 |
| Pregnancy, puerperium and perinatal conditions | ||
| Afterbirth Pain | 1/18 (5.6%) | 1 |
| Psychiatric disorders | ||
| Anxiety | 1/18 (5.6%) | 1 |
| Renal and urinary disorders | ||
| Hematuria | 1/18 (5.6%) | 1 |
| Incontinence | 1/18 (5.6%) | 1 |
| Reproductive system and breast disorders | ||
| Vaginal Laceration | 3/18 (16.7%) | 3 |
| Nipple Pain | 1/18 (5.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Crackles Lung | 1/18 (5.6%) | 1 |
| Dyspnea | 1/18 (5.6%) | 1 |
| Epistaxis | 1/18 (5.6%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Hyperhidrosis | 1/18 (5.6%) | 1 |
| Rash | 1/18 (5.6%) | 1 |
| Vascular disorders | ||
| Haematoma | 1/18 (5.6%) | 1 |
| Lymphangitis | 1/18 (5.6%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Denise Tilton, RN, MHA, Director Clinical Affairs |
|---|---|
| Organization | GTC Biotherapeutics |
| Phone | 508-370-5257 |
| denise.tilton@gtc-bio.com |
- GTC AT HD 012-04