Antithrombin III DeficiencyPhase 3NCT00110513
Recombinant Human Antithrombin (rhAT) in Patients With Hereditary Antithrombin Deficiency Undergoing Surgery or Delivery
A Phase 3 study testing Recombinant human antithrombin (rhAT) in people with Antithrombin III Deficiency, run by rEVO Biologics at 17 sites in 8 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Antithrombin III Deficiency
- What is being tested?
- Recombinant human antithrombin (rhAT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 17 sitesin 8 countries
- Study dates
- Apr 2005to Jul 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
17 sites in 8 countries.
17 sites in 8 countries
United Kingdom7 sites
Study site
Cambridge
Study site
Chichester, West Sussex
Study site
Exeter, Devon
Study site
Glasgow
Study site
London
Study site
Nottingham
Study site
Plymouth
United States3 sites
Study site
New Haven, Connecticut
Study site
New York, New York
Study site
St Louis, Missouri
About this study
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
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.
Read the 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
- Being tested
- Recombinant human antithrombin (rhAT)
- Keywords
- Antithrombin Deficiency, Congenital or Hereditary, Antithrombin III Deficiency, ATIII, Hereditary Antithrombin Deficiency (HD)
- Medical subject headings
- Antithrombin III Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human antithrombin (rhAT)Biological
Also called Recombinant human antithrombin (Tradename: ATryn)
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.
| Study group | Role | What they receive |
|---|---|---|
| Recombinant Human Antithrombin (rhAT) Infusion | Experimental | Intravenous infusion of rhAT. Receives: Biological: Recombinant human antithrombin (rhAT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During treatment and follow up period of 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2005 (estimated)
- Study startApr 2005
- Primary completionMay 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antithrombin III DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- rEVO Biologics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert C Tait, MD, Principal investigator, Glasgow Royal Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110513
- Sponsor's protocol ID
- GTC AT HD 012-04
- Status last verified
- Aug 2012
- First submitted
- 10 May 2005
- Last updated
- 17 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24335249
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00110513
- Acronym / sponsor ID
- GTC AT HD 012-04
- Conditions
- Antithrombin III Deficiency
- Keywords
- Antithrombin Deficiency, Congenital or Hereditary, Antithrombin III Deficiency, ATIII, Hereditary Antithrombin Deficiency (HD)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- rEVO BiologicsIndustry (pharma, biotech, devices)
- Study start
- Apr 2005
- Primary completion
- May 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 11 May 2005 (estimated)
- Results
- Posted 11 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant Human Antithrombin (rhAT) Infusion | Experimental | Biological: Recombinant human antithrombin (rhAT)Intravenous infusion of rhAT. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant human antithrombin (rhAT)Also: Recombinant human antithrombin (Tradename: ATryn)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. | Biological | Recombinant Human Antithrombin (rhAT) Infusion |
Primary outcome
Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Venous Thrombosis (DVT)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24335249DeJongh 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert C Tait, MD principal investigator
Glasgow Royal Infirmary
17 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Recombinant human antithrombin (rhAT) in people with Antithrombin III Deficiency, run by rEVO Biologics at 17 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United Kingdom, United States, Canada, Australia, Austria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Thromboembolic Events Acute Deep Venous Thrombosis (DVT) and/or Thromboembolic Events Other Than Acute Deep Venous Thrombosis (DVT) (time frame: During treatment and follow up period of 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00110513, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2012.