Antithrombin Deficiency, Congenital
Conditions
Keywords
Antithrombin Deficiency, Congenital, Antithrombin III Deficiency
Brief summary
Patients with hereditary antithrombin (AT) deficiency are at increased risk of venous thrombosis and pulmonary embolism, particularly during certain high risk procedures. The trial is focusing on patients with confirmed hereditary antithrombin deficiency who are undergoing a surgical procedure or induced/spontaneous labor and delivery. The study will test the safety and efficacy of recombinant human antithrombin (rhAT) by infusing rhAT prior to, during and following the period of risk or surgical procedure.
Detailed description
Objectives : 1. Assess the safety of recombinant antithrombin (rhAT) in hereditary antithrombin (AT) deficient patients. 2. Assess the incidence of acute deep venous thrombosis(DVT) alone in patients with hereditary antithrombin (AT) deficiency in situations usually associated with a high risk for thromboembolic events after increasing and targeting functional AT activity at \>80% and \< 120% of normal by prophylactic IV administration of rhAT. 3. Clinically assess and determine the relevance of thromboembolic events other than acute DVT to rhAT administration.
Interventions
BIOLOGICALRecombinant Human Antithrombin (rhAT)
Biological/Vaccine: Recombinant human antithrombin(rhAT) Phase III clinical trial.
Sponsors
rEVO Biologics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Have congenital AT deficiency with a personal or family history of venous thrombotic events. * Have a history of congenital AT deficiency that includes 2 or more plasma AT activity levels of ≤ 60% normal. * Are scheduled to have an elective procedure known to be associated with a high risk for occurrence of Deep Venous Thrombosis (DVT). This will include surgical patients or pregnant patients scheduled for cesarean section or delivery induction. In addition, hospitalized pregnant HD patients in active labor will be allowed into the study. * Are at least 18 years of age, not exceeding 70 years of age. * Have signed an informed consent form. * Have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline. This only applies to female surgical patients (not scheduled for cesarean section) of childbearing potential. * Are able to comply with the requirements of the study protocol.
Exclusion criteria
* Patients who have a diagnosis of hereditary APC resistance, Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation (G20210A), or acquired (lupus anticoagulant) thrombophilic disorder. * Patients who are scheduled for a neurosurgical procedure or open-heart surgery. * Patients who have an underlying medical condition, which in the opinion of the investigator, could complicate the assessment of the incidence of DVT. * Patients who have a known allergy to goats or goat products. * Patients who have participated in a study employing an investigational drug within 30 days of the start of their participation in the current trial. * Patients using fondaparinux sodium, or are expected to be treated with fondaparinux sodium during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Vein Thrombosis (DVT). | Baseline, last day of dosing and day 7 (+ or - 1 day) | Observation for clinical signs and symptoms of thromboembolic events are evaluated for acute deep vein thrombosis (DVT) using duplex ultrasonography and/or other imaging tests to confirm clinical signs/symptoms. Duplex ultrasonography was performed at baseline, last day of dosing and day 7 (+ or -1 day). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Assessment of Thromboembolism by Physical Examination. | 30 days after last dose | The investigators evaluated patients for any clinical signs of thromboembolism by physical examination. |
Countries
France, Germany, Italy, Sweden, United Kingdom, United States
Participant flow
Recruitment details
GTC Biotherapeutics (GTC) established clinical trials sites in hospitals located in the United States and Europe. GTC provided an international clinical team to support site registration requirements once a patient was identified for treatment. The clinical trial started in December 2002 and completed in February 2004.
Pre-assignment details
Fourteen hereditary antithrombin (AT) deficient patients were enrolled into the trial. The patients included surgical (N = 5) and delivery patients (N = 9) who were treated with recombinant human antithrombin (rhAT) replacement therapy.
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Human Antithrombin (rhAT) Infusion Following a baseline evaluation phase hereditary AT deficient patients(previously documented AT activity \< or equal to 60% of normal)scheduled for surgery ,cesarean section or vaginal delivery were planned to be treated prophylactically with rhAT. Dosing with rhAT was to be individualized with an initial loading dose, followed by a continuous maintenance infusion dose, intended to increase and target antithrombin (AT) activity levels \> 80% and \< 120% of normal. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Recombinant Human Antithrombin (rhAT) Infusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age Continuous | 36.7 years STANDARD_DEVIATION 13.6 |
| Antithrombin (AT) activity level < or equal to 60% | 14 Participants |
| Prior history of venous thrombotic events | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment Europe | 12 participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 14 |
| serious Total, serious adverse events | 6 / 14 |
Outcome results
Primary
Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Vein Thrombosis (DVT).
Observation for clinical signs and symptoms of thromboembolic events are evaluated for acute deep vein thrombosis (DVT) using duplex ultrasonography and/or other imaging tests to confirm clinical signs/symptoms. Duplex ultrasonography was performed at baseline, last day of dosing and day 7 (+ or -1 day).
Time frame: Baseline, last day of dosing and day 7 (+ or - 1 day)
Population: 14 patients who received at least 1 dose of rhAT were included in the Safety population. During the central review of the duplex ultrasound, 1 delivery patient was diagnosed with a DVT at baseline, and was not evaluable for efficacy, the patient was excluded from the PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Human Antithombin (rhAT) Infusion | Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Vein Thrombosis (DVT). | 1 participants |
Secondary
Local Assessment of Thromboembolism by Physical Examination.
The investigators evaluated patients for any clinical signs of thromboembolism by physical examination.
Time frame: 30 days after last dose
Population: 14 patients were included in the trial and treated with rhAT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Human Antithombin (rhAT) Infusion | Local Assessment of Thromboembolism by Physical Examination. | 0 Participants in study |