ATIII DeficiencyPhase 2NCT02103114
Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery
A Phase 2 study testing Anti-thrombin III in people with ATIII Deficiency, run by Duke University at 1 site in United States.
Trial summary
The purpose of this study is to test whether the administration of ATIII during the intra-operative period results in improved anticoagulation for cardiopulmonary bypass (CPB) and an attenuation of the activation of the coagulation cascade, as represented by a decrease in fibrin degradation products. Read more about this study
- Who is it for?
- Ages Up to 7 months
- Conditions the study is for
- ATIII Deficiency
- What is being tested?
- Anti-thrombin III
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to 1 Jul 2016
- Phase
- Phase 2
- 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 Up to 7 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All patients less than 7 months of age going for cardiac surgery that will require cardiopulmonary bypass (CPB) with a documented ATIII level below 70%
Who cannot join
- Less than 2.5kg
- Known or suspected hereditary ATIII deficiency (family history of venous thrombosis with decreased plasma levels of ATIII and no other potential causes of acquired decreased ATIII)
- On Ecmo (extracorporeal membrane oxygenation ) at time of surgery
- Known history of thrombosis
- Renal failure as described by the pediatric RIFLE criteria
- H/o intracranial hemorrhage
Show all 10Show fewer
- Prematurity less than 37 weeks estimated gestational age
- Previously diagnosed pro-thrombotic or hemorrhagic disorder
- Prior ATIII supplementation
- Prior therapeutic anticoagulant use
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double Blind Randomized Placebo-controlled Study in Children (<6mo) Comparing the Effects of Anti-thrombin III (ATIII) or Placebo on the Coagulation System in Infants With Known Low ATIII Levels Undergoing Open Congenital Cardiac Surgery
The purpose of this study is to test whether the administration of ATIII during the intra-operative period results in improved anticoagulation for cardiopulmonary bypass (CPB) and an attenuation of the activation of the coagulation cascade, as represented by a decrease in fibrin degradation products. The investigators believe this benefit would extend into the post-operative period resulting in a decreased incidence of thrombosis generation, as represented by a decrease in fibrin degradation products in the ICU period.
Read the detailed description
If Preoperative ATIII functional assay level is less than 70% patients would be enrolled and randomized to either Placebo (normal saline) or ATIII.
- Conditions
- ATIII Deficiency
- Being tested
- Anti-thrombin III, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-thrombin IIIDrug
Also called Thrombate III
Intraoperatively- (correcting to 100%) according to the following formula:
Units required = ((100%- baseline ATIII level*%) X body weight)/1.4
- expressed as a % normal level based on functional ATIII assay
PlaceboOther
Normal saline placebo
| Study group | Role | What they receive |
|---|---|---|
| Anti-thrombin III | Experimental | Not described Receives: Drug: Anti-thrombin III |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU)
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at Time 5 (on arrival in ICU).
Measured: Time 5 (on arrival in ICU)
Secondary outcomes (24)
Difference in the Mean and SD of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Times 5-Time 7 (ICU Arrival to Post Operative Day 4)
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at times 5-Time 7 (ICU arrival to Post Operative Day 4)
Measured: ICU arrival (Time 5) to Time 7 (Post-operative Day 4)
Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean of the ATIII (functional assay) of the control and ATIII groups at T1, T2, T3, T5, T6 and T7 (Baseline, 30 min after study drug, 30 min on CPB, Arrival in ICU, POD 2, and POD 4). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage.
Measured: T1, T2, T3, T5, T6 and T7
Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the ATIII (functional assay) of the control and ATIII groups at T4 (just prior to coming off of CPB). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage.
Measured: T4 (just prior to coming off of CPB)
Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the D dimer of the control and ATIII groups at T1 (Baseline), T5 (Arrival in Intensive Care Unit), T6 (Post-Operative Day 2) and T7 (Post-Operative Day 4).
Measured: T1, T5, T6 and T7
Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.
Evidence of a decreased amount of residual heparin at the Intensive Care Unit arrival time point (T5) represented by a decreased anti factor Xa level.
Measured: T5 (Intensive Care Unit Arrival)
Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group
Evidence of decreased inflammation represented by a decrease in inflammatory markers in the ATIII group.
Measured: Baseline (T1) to Post-Operative Day 4 (T7)
Total Dose of Heparin While on Cardiopulmonary Bypass
Total dose of Heparin while on Cardiopulmonary Bypass
Measured: T1 (Baseline) to T5 (Arrival in ICU)
Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)
Protamine dose determined by Hemostasis Management system machine (mg/kg)
Measured: T1 (Baseline) to T5 (Arrival in ICU)
Total Volume of Blood Products While on CPB
Total volume of blood products exposed intraoperatively including the pump prime (ml/kg)
Measured: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Time From Protamine Administration to Skin Dressing
Time from protamine administration to skin dressing
Measured: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Total Volume of Fresh Frozen Plasma Given Prior to CPB
Total volume of Fresh Frozen Plasma given prior to CPB, including the pump prime (ml/kg)
Measured: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Measured: Baseline (Intraoperatively)
Volume of Postoperative Blood Loss
Volume of postoperative blood loss from 10min post protamine administration to 24 hour post protamine administration- (ml/kg)
Measured: From 10min post protamine administration to 24 hour post protamine administration
Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters
Chest Tube output (protamine time plus 24 hours) in milliliters
Measured: protamine time plus 24 hours
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group
Number of packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units transfused 24 hours post-operatively for each group (not total units transfused for each subject)
Measured: 24 Hours Post-Operatively
Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group
Number of total blood product units (including packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units) transfused 24 hours post-operatively for each group (not total units transfused for each subject)
Measured: 24 Hours Post-Operatively
Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively
Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively
Measured: Intraoperatively
Length of Post Operative Ventilation in Days
Length of post operative ventilation in days
Measured: ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)
Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively
Study the safety profile of dosing the ATIII by monitoring the incidence of extracorporeal membrane oxygenation (ECMO) support within 24 hours postoperatively.
Measured: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence of Mediastinal Exploration Within 24 Hours Postoperatively
Study the safety profile of dosing the ATIII by monitoring the incidence of mediastinal exploration within 24 hours postoperatively
Measured: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence (Number) of Thrombotic Events Documented
Study the safety profile of dosing the ATIII by monitoring the incidence (number) of thrombotic events documented.
Measured: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria
Study the safety profile of dosing the ATIII by monitoring the incidence of new onset renal failure, defined by stage 3 of the Acute Kidney Injury Network (AKIN) criteria.
- Serum creatinine increase ≥26.5 μmol/l (≥0.3 mg/dl) or increase to 1.5-2.0-fold from baseline, urine output <0.5 ml/kg/h for 6 hours
- Serum creatinine increase >2.0-3.0-fold from baseline, urine output <0.5 ml/kg/h for 12 hours
- Serum creatinine increase >3.0-fold from baseline or serum creatinine ≥354 μmol/l (≥4.0 mg/dl) with an acute increase of at least 44 μmol/l (0.5 mg/dl) or need for Renal replacement therapy (RRT), urine output <0.3 ml/kg/h for 24 h or anuria for 12 hours or need for RRT
Measured: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage
Study the safety profile of dosing the ATIII by monitoring the incidence (number) of newly diagnosed intracranial hemorrhage
Measured: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Length of Time to Delayed Sternal Closure Measured in Days
Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure measured in days
Measured: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2014 (estimated)
- Study startJun 2014
- Primary completion27 Jun 2016
- Study completion1 Jul 2016
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.
- Other trials for ATIII DeficiencyStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Grifols Biologicals, LLC
- Responsible party
- Sponsor
- Investigators
- Edmund Jooste, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02103114
- Sponsor's protocol ID
- Pro00051186
- Status last verified
- Nov 2019
- First submitted
- 1 Apr 2014
- Last updated
- 25 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Randomized Placebo-controlled Study in Children (<6mo) Comparing the Effects of Anti-thrombin III (ATIII) or Placebo on the Coagulation System in Infants With Known Low ATIII Levels Undergoing Open Congenital Cardiac Surgery
- ClinicalTrials.gov ID
- NCT02103114
- Acronym / sponsor ID
- Pro00051186
- Conditions
- ATIII Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Grifols Biologicals, LLC
- Study start
- Jun 2014
- Primary completion
- 27 Jun 2016 (actual)
- Study completion
- 1 Jul 2016 (actual)
- First posted
- 3 Apr 2014 (estimated)
- Results
- Posted 26 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test whether the administration of ATIII during the intra-operative period results in improved anticoagulation for cardiopulmonary bypass (CPB) and an attenuation of the activation of the coagulation cascade, as represented by a decrease in fibrin degradation products. The investigators believe this benefit would extend into the post-operative period resulting in a decreased incidence of thrombosis generation, as represented by a decrease in fibrin degradation products in the ICU period.
Detailed description
If Preoperative ATIII functional assay level is less than 70% patients would be enrolled and randomized to either Placebo (normal saline) or ATIII.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anti-thrombin III | Experimental | Drug: Anti-thrombin III |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- Up to 7 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- All patients less than 7 months of age going for cardiac surgery that will require cardiopulmonary bypass (CPB) with a documented ATIII level below 70%
Key exclusion criteria (10 listed)
- Less than 2.5kg
- Known or suspected hereditary ATIII deficiency (family history of venous thrombosis with decreased plasma levels of ATIII and no other potential causes of acquired decreased ATIII)
- On Ecmo (extracorporeal membrane oxygenation ) at time of surgery
- Known history of thrombosis
- Renal failure as described by the pediatric RIFLE criteria
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 |
|---|---|---|
| Anti-thrombin IIIAlso: Thrombate IIIIntraoperatively- (correcting to 100%) according to the following formula: Units required = ((100%- baseline ATIII level*%) X body weight)/1.4 * expressed as a % normal level based on functional ATIII assay | Drug | Anti-thrombin III |
| PlaceboNormal saline placebo | Other | Placebo |
Primary outcome
Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU)
Time frame: Time 5 (on arrival in ICU)
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at Time 5 (on arrival in ICU).
24 secondary outcomes
Difference in the Mean and SD of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Times 5-Time 7 (ICU Arrival to Post Operative Day 4)
Time frame: ICU arrival (Time 5) to Time 7 (Post-operative Day 4)
Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7
Time frame: T1, T2, T3, T5, T6 and T7
Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4
Time frame: T4 (just prior to coming off of CPB)
Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7
Time frame: T1, T5, T6 and T7
Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.
Time frame: T5 (Intensive Care Unit Arrival)
Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group
Time frame: Baseline (T1) to Post-Operative Day 4 (T7)
Total Dose of Heparin While on Cardiopulmonary Bypass
Time frame: T1 (Baseline) to T5 (Arrival in ICU)
Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)
Time frame: T1 (Baseline) to T5 (Arrival in ICU)
Total Volume of Blood Products While on CPB
Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Time From Protamine Administration to Skin Dressing
Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Total Volume of Fresh Frozen Plasma Given Prior to CPB
Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Time frame: Baseline (Intraoperatively)
Volume of Postoperative Blood Loss
Time frame: From 10min post protamine administration to 24 hour post protamine administration
Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters
Time frame: protamine time plus 24 hours
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group
Time frame: 24 Hours Post-Operatively
Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group
Time frame: 24 Hours Post-Operatively
Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively
Time frame: Intraoperatively
Length of Post Operative Ventilation in Days
Time frame: ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)
Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence of Mediastinal Exploration Within 24 Hours Postoperatively
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence (Number) of Thrombotic Events Documented
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Length of Time to Delayed Sternal Closure Measured in Days
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for ATIII Deficiency
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Efficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery
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Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass
Acquired Antithrombin Deficiency
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Antithrombin III Deficiency
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.
Edmund Jooste, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anti-thrombin III in people with ATIII Deficiency, run by Duke University at 1 site in United States.
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 1 inclusion and 10 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 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 26 Jul 2017). 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?
Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU) (time frame: Time 5 (on arrival in ICU)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2019.