ATIII Deficiency Clinical Trial
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
| NCT number | NCT02103114 |
| Other study ID # | Pro00051186 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | June 2014 |
| Est. completion date | July 1, 2016 |
| Verified date | November 2019 |
| Source | Duke University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 45 |
| Est. completion date | July 1, 2016 |
| Est. primary completion date | June 27, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 7 Months |
| Eligibility |
Inclusion Criteria: - 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% Exclusion Criteria: - 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 - Prematurity less than 37 weeks estimated gestational age - Previously diagnosed pro-thrombotic or hemorrhagic disorder - Prior ATIII supplementation - Prior therapeutic anticoagulant use |
| Country | Name | City | State |
|---|---|---|---|
| United States | Duke University | Durham | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Duke University | Grifols Biologicals, LLC |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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). | Time 5 (on arrival in ICU) | |
| Secondary | 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) | ICU arrival (Time 5) to Time 7 (Post-operative Day 4) | |
| Secondary | 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. | T1, T2, T3, T5, T6 and T7 | |
| Secondary | 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. | T4 (just prior to coming off of CPB) | |
| Secondary | 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). | T1, T5, T6 and T7 | |
| Secondary | 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. | T5 (Intensive Care Unit Arrival) | |
| Secondary | 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. | Baseline (T1) to Post-Operative Day 4 (T7) | |
| Secondary | Total Dose of Heparin While on Cardiopulmonary Bypass | Total dose of Heparin while on Cardiopulmonary Bypass | T1 (Baseline) to T5 (Arrival in ICU) | |
| Secondary | Protamine Dose Determined by Hemostasis Management System Machine (mg/kg) | Protamine dose determined by Hemostasis Management system machine (mg/kg) | T1 (Baseline) to T5 (Arrival in ICU) | |
| Secondary | Total Volume of Blood Products While on CPB | Total volume of blood products exposed intraoperatively including the pump prime (ml/kg) | Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) | |
| Secondary | Time From Protamine Administration to Skin Dressing | Time from protamine administration to skin dressing | Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) | |
| Secondary | 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) | Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) | |
| Secondary | Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively | Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively | Baseline (Intraoperatively) | |
| Secondary | Volume of Postoperative Blood Loss | Volume of postoperative blood loss from 10min post protamine administration to 24 hour post protamine administration- (ml/kg) | From 10min post protamine administration to 24 hour post protamine administration | |
| Secondary | Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters | Chest Tube output (protamine time plus 24 hours) in milliliters | protamine time plus 24 hours | |
| Secondary | 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) | 24 Hours Post-Operatively | |
| Secondary | 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) | 24 Hours Post-Operatively | |
| Secondary | Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively | Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively | Intraoperatively | |
| Secondary | Length of Post Operative Ventilation in Days | Length of post operative ventilation in days | ICU arrival (Time 5) to Time 7 (Post-Operative Day 4) | |
| Secondary | 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. | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | |
| Secondary | 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 | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | |
| Secondary | Incidence (Number) of Thrombotic Events Documented | Study the safety profile of dosing the ATIII by monitoring the incidence (number) of thrombotic events documented. | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | |
| Secondary | 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 |
Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | |
| Secondary | 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 | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | |
| Secondary | 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 | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) |