Trial Outcomes & Findings for Assess Incidence of Deep Vein Thrombosis(DVT)Following Administration of Recombinant Human Antithrombin (rhAT) to Hereditary Antithrombin(AT) Deficient Patients in High Risk Situations. (NCT NCT00056550)

Last Updated: 2012-10-16

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

14 participants

Primary outcome timeframe

Baseline, last day of dosing and day 7 (+ or - 1 day)

Results posted on

2012-10-16

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Recombinant Human Antithrombin (rhAT) Infusion Following a baseline evaluation phase hereditary antithrombin(AT)deficient patients scheduled for surgery, cesarean section or vaginal delivery were planned to be treated prophylactically with recombinant human antithrombin (rhAT). Dosing with recombinant human antithrombin (rhAT) was individualized with an initial intravenous loading dose, followed by a continuous intravenous infusion dose, intended to target and maintain antithrombin (AT) activity levels \> 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 were based on the results of AT activity level determinations performed prior to and during the treatment.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Assess Incidence of Deep Vein Thrombosis(DVT)Following Administration of Recombinant Human Antithrombin (rhAT) to Hereditary Antithrombin(AT) Deficient Patients in High Risk Situations.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recombinant Human Antithrombin (rhAT) Infusion n=14 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age Continuous	36.7 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment Europe	12 participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants
Prior history of venous thrombotic events	14 Participants n=5 Participants
Antithrombin (AT) activity level < or equal to 60%	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Recombinant Human Antithombin (rhAT) Infusion n=14 Participants Following a baseline evaluation phase hereditary antithrombin (AT) deficient patients scheduled for surgery, cesarean section or vaginal delivery were planned to be treated prophylactically with recombinant human antithrombin (rhAT). Dosing with rhAT was to be individualized with an initial loading dose, followed by a continuous maintenance infusion dose, intended to target and maintain antithrombin (AT) activity levels \> 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.
Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Vein Thrombosis (DVT).	1 participants

SECONDARY outcome

Timeframe: 30 days after last dose

Population: 14 patients were included in the trial and treated with rhAT.

The investigators evaluated patients for any clinical signs of thromboembolism by physical examination.

Outcome measures

Outcome measures
Measure	Recombinant Human Antithombin (rhAT) Infusion n=14 Participants Following a baseline evaluation phase hereditary antithrombin (AT) deficient patients scheduled for surgery, cesarean section or vaginal delivery were planned to be treated prophylactically with recombinant human antithrombin (rhAT). Dosing with rhAT was to be individualized with an initial loading dose, followed by a continuous maintenance infusion dose, intended to target and maintain antithrombin (AT) activity levels \> 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.
Local Assessment of Thromboembolism by Physical Examination.	0 Participants in study

Adverse Events

Recombinant Human Antithrombin (rhAT) Infusion

Serious events: 6 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Recombinant Human Antithrombin (rhAT) Infusion n=14 participants at risk 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.
General disorders Fever	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Vascular disorders Thrombophlebitis Deep	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Cardiac disorders Hypotension	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Blood and lymphatic system disorders Hemorrhage NOS	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Nervous system disorders Convulsions Grand Mal	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Musculoskeletal and connective tissue disorders Fracture Trauma	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.

Other adverse events

Other adverse events
Measure	Recombinant Human Antithrombin (rhAT) Infusion n=14 participants at risk 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.
Cardiac disorders Hypotension	7.1% 1/14 • Number of events 5 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
General disorders Post-operative pain	7.1% 1/14 • Number of events 4 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Blood and lymphatic system disorders Anemia	7.1% 1/14 • Number of events 4 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 2 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 2 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
General disorders Infection	7.1% 1/14 • Number of events 2 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Blood and lymphatic system disorders Hematoma	7.1% 1/14 • Number of events 3 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.
Infections and infestations Fever	7.1% 1/14 • Number of events 1 • Adverse event data was collected for duration of study up to 90 days post study drug administration. All 14 patients who received rhAT were evaluated for the occurrence of treatment-emergent AEs from the time of their initial bolus dose up to and including 30 days after administration of their last dose of rhAT and for the development of antibodies to rhAT out to 90 days following treatment.

Additional Information

Denise Tilton, RN, MHA, Director Clinical Development

GTC Biotherapeutics

Phone: 508-370-5257

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place