The Epidemiology of Bleeding and Clotting in Patients Undergoing Heart Transplantation, Coronary Artery Bypass Graft Surgery,or Implantation of Left Ventricular Assist Devices

Congestive Heart Failure Clinical Trial

Official title:

The Epidemiology of Bleeding and Clotting in Patients Undergoing Heart Transplantation, Coronary Artery Bypass Graft Surgery,or Implantation of Left Ventricular Assist Devices

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01481012
• Other study ID #: 08-1093 PD
• Secondary ID: 5P50HL077096
• Status: Terminated
• Phase: N/A
• First received: November 7, 2011
• Last updated: November 23, 2011
• Start date: January 2006
• Est. completion date: July 2007

Study information

• Verified date: November 2011
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to obtain data or information on how blood clotting factors are activated during open heart surgery. In particular, the investigators are interested in how blood clotting factors are activated by the heart-lung bypass machine and by left ventricular assist devices (LVAD). Patients on these two machines have an increased risk of bleeding and blood clot formation. This is because both machines stimulate the intrinsic coagulation pathway, one of the chemical pathways that cause blood to clot. The process of surgery itself also stimulates the "extrinsic coagulation pathway," the other chemical pathway that causes blood to clot. Stimulating these coagulation pathways can use up the body's clotting factors. As a result, patients may be at risk for both bleeding and blood clot formation. The investigators would like to study how the blood factors are activated during and after surgery, to help develop treatments to prevent bleeding and clot formation.

Description:

This is a prospective, multi-center, observational study to characterize the epidemiology of bleeding and clotting in patients with underlying systolic ventricular dysfunction undergoing heart transplantation, CABG surgery, or implantation of left ventricular assist devices. Patients will be followed for up to 28 days post-implant, post-CABG, post-heart transplant, or until hospital discharge, whichever comes first. There will be no randomization for this observational study.

We will enroll 100 patients (we expect the distribution to be approximately 30 per Groups I

• III, but no cap per group, and 10 for Group IV) who have been scheduled to undergo CPB within 24 hours for one of the following:

Group I: Cardiopulmonary Bypass + Heart Transplantation CPB for orthotopic heart transplantation (excluding any patients with VADs)

Group II: Cardiopulmonary Bypass + Pulsatile LVAD CPB for implantation of a Thoratec HeartMate® I LVAD (for destination therapy or bridge to transplantation)

Group III: Cardiopulmonary Bypass + Continuous Flow LVAD CPB for implantation of an axial flow or centrifugal flow LVAD (for destination therapy or bridge to transplantation) (e.g. HeartMate® II, DeBakey VAD® or VentrAssist® LVAS)

Group IV: Cardiopulmonary Bypass + CABG/Valve Surgery CPB for CABG or valve surgery

Heart transplantation and perioperative care will be performed in accordance with the standard of care at the clinical center. Pulsatile LVAD (e.g. HeartMate® I) implantation and perioperative management will be performed in accordance with the standard of care at the clinical center, and guided by the HeartMate® I Directions for Use. Continuous flow LVAD implantation and perioperative management will be performed in accordance with the standard of care at the clinical center, and guided by the specific VAD manufacturer's Directions for Use. CABG surgery and perioperative care will be performed in accordance with the standard of care at the clinical center.

We anticipate that enrollment will be completed over a six-month period.

We hypothesize that the initial activation of the intrinsic pathway of coagulation is attenuated for several days in patients undergoing CPB for CABG alone; however, in subjects undergoing CPB with VAD implantation or cardiac transplantation, activation of this pathway is biphasic and sustained.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 94
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent, release of medical information, and HIPAA forms;

2. Age greater than or equal to 18 years;

3. Male, postmenopausal female, or female who may become pregnant but is using adequate contraceptive precautions (defined as oral contraceptive, intrauterine devices, surgical contraception or a combination of a condom and a spermicide), with negative pregnancy test;

4. Admitted to the clinical center at the time of enrollment;

5. Approved and scheduled to undergo one of the following within 24 hours of enrollment:

• Orthotopic heart transplantation

• CABG and/or valve surgery on CPB; these patients must have an LV ejection fraction of =35%

• Implantation of a pulsatile LVAD (e.g.Thoratec HeartMate® I LVAD) for destination therapy or bridge to transplantation

• Implantation of a continuous flow LVAD (e.g. HeartMate® II, DeBakey VAD® or VentrAssist® LVAS) for destination therapy or bridge to transplantation

Exclusion Criteria:

1. History of a platelet disorder;

2. History of a known, or an inherited, or an acquired coagulation disorder in the study subject;

3. Stroke within 30 days prior to enrollment;

4. Allergy to heparin or protamine;

5. Participation in a clinical investigational intervention trial, with the exception of an investigational VAD trial, at the time of enrollment;

6. Received investigational intervention within 30 days of enrollment, with the exception of an investigational VAD trial

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Jewish Hospital	Louisville	Kentucky
United States	University of Wisconsin Hospital	Madison	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia Presbyterian Medical Center	New York	New York
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	LDS Hospital	Salt Lake City	Utah
United States	Sharp Memorial Hospital	San Diego	California
United States	Sacred Heart Medical Center	Spokane	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	At time of surgery (before initiation of Cardiopulmonary Bypass)	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	At time of surgery (dismantling the sterile environment)	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 1	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	At time of surgery	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day12 (while remaining in hosp)	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 16 (while remaining in hosp)	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 20 (while remaining in hosp)	No
Primary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 24 (while remaining in hosp)	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	At time of surgery (dismantling of the sterile environment)	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 1	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 12 (± 3 days) (or at time of discharge, whichever comes first)	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 20 (± 3 days) (or at time of discharge, whichever comes first)	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 28 (± 3 days) (or at time of discharge, whichever comes first)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	At time of surgery ( before initiation of Cardiopulmonary Bypass)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	At time of surgery (dismantling the sterile environment)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 1	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	At time of surgery	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 12 (while remaining in hosp)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 16 (while remaining in hosp)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 20 (while remaining in hosp)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 24 (while remaining in hosp)	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 28 (± 3 days) (or at time of discharge, whichever comes first)	No
Secondary	Serious Adverse Events	The incidence and frequency of all expected and unexpected serious adverse events will be determined. Since this is an observational study, there will be no adverse events directly attributable to a study intervention. However, adverse events that may potentially contribute to the risk or course of bleeding and clotting in patients undergoing heart transplantation, CABG surgery, or implantation of LVADs will be monitored. The adverse events are defined according to the definitions recently finalized by the INTERMACS LVAD registry.	Duration of the Study, up to 28 days post-implant, post-CABG, post heart-transplant, or until hospital discharge, whichever comes first.	No
Secondary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 2	No
Secondary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 3	No
Secondary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombo Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 4	No
Secondary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombo Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 5	No
Secondary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 6	No
Secondary	Thrombin Generation Markers	We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.	Post-operative day 7	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 2	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 3	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 4	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 5	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 6	No
Secondary	Bleeding	Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.	Post-operative day 7	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 2	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 3	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 4	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 5	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 6	No
Secondary	Coagulation Markers	Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.	Post-operative day 7	No