Clinical trial NCT01481012: The Epidemiology of Bleeding and Clotting in Patients Undergoing Heart Transplantation, Coronary Artery Bypass Graft Surgery,or Implantation of Left Ventricular Assist Devices
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
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Congestive Heart Failure
Keywords: Heart transplantation
Coronary artery bypass graft (CABG) surgery
Left ventricular assist device implantation surgeries
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-11-29
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with underlying systolic ventricular dysfunction who will undergo heart transplantation, CABG surgery, implantation of a pulsatile LVAD, or implantation of a continuous flow LVAD (as destination therapy or bridge to transplantation) within 24 hours of enrollment, are candidates for this study.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Thrombin Generation Markers
timeFrame: At time of surgery (before initiation of Cardiopulmonary Bypass)
measure: Thrombin Generation Markers
timeFrame: At time of surgery (dismantling the sterile environment)
measure: Thrombin Generation Markers
timeFrame: Post-operative day 1
measure: Thrombin Generation Markers
timeFrame: At time of surgery
measure: Thrombin Generation Markers
timeFrame: Post-operative day12 (while remaining in hosp)
measure: Thrombin Generation Markers
timeFrame: Post-operative day 16 (while remaining in hosp)
measure: Thrombin Generation Markers
timeFrame: Post-operative day 20 (while remaining in hosp)
measure: Thrombin Generation Markers
timeFrame: Post-operative day 24 (while remaining in hosp)
Secondary outcomes:
measure: Bleeding
timeFrame: At time of surgery (dismantling of the sterile environment)
measure: Bleeding
timeFrame: Post-operative day 1
measure: Bleeding
timeFrame: Post-operative day 12 (± 3 days) (or at time of discharge, whichever comes first)
measure: Bleeding
timeFrame: Post-operative day 20 (± 3 days) (or at time of discharge, whichever comes first)
measure: Bleeding
timeFrame: Post-operative day 28 (± 3 days) (or at time of discharge, whichever comes first)
measure: Coagulation Markers
timeFrame: At time of surgery ( before initiation of Cardiopulmonary Bypass)
measure: Coagulation Markers
timeFrame: At time of surgery (dismantling the sterile environment)
measure: Coagulation Markers
timeFrame: Post-operative day 1
measure: Coagulation Markers
timeFrame: At time of surgery
measure: Coagulation Markers
timeFrame: Post-operative day 12 (while remaining in hosp)
measure: Coagulation Markers
timeFrame: Post-operative day 16 (while remaining in hosp)
measure: Coagulation Markers
timeFrame: Post-operative day 20 (while remaining in hosp)
measure: Coagulation Markers
timeFrame: Post-operative day 24 (while remaining in hosp)
measure: Coagulation Markers
timeFrame: Post-operative day 28 (± 3 days) (or at time of discharge, whichever comes first)
measure: Serious Adverse Events
timeFrame: Duration of the Study, up to 28 days post-implant, post-CABG, post heart-transplant, or until hospital discharge, whichever comes first.
measure: Thrombin Generation Markers
timeFrame: Post-operative day 2
measure: Thrombin Generation Markers
timeFrame: Post-operative day 3
measure: Thrombin Generation Markers
timeFrame: Post-operative day 4
measure: Thrombin Generation Markers
timeFrame: Post-operative day 5
measure: Thrombin Generation Markers
timeFrame: Post-operative day 6
measure: Thrombin Generation Markers
timeFrame: Post-operative day 7
measure: Bleeding
timeFrame: Post-operative day 2
measure: Bleeding
timeFrame: Post-operative day 3
measure: Bleeding
timeFrame: Post-operative day 4
measure: Bleeding
timeFrame: Post-operative day 5
measure: Bleeding
timeFrame: Post-operative day 6
measure: Bleeding
timeFrame: Post-operative day 7
measure: Coagulation Markers
timeFrame: Post-operative day 2
measure: Coagulation Markers
timeFrame: Post-operative day 3
measure: Coagulation Markers
timeFrame: Post-operative day 4
measure: Coagulation Markers
timeFrame: Post-operative day 5
measure: Coagulation Markers
timeFrame: Post-operative day 6
measure: Coagulation Markers
timeFrame: Post-operative day 7
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Spokane
country: United States
facility: Sacred Heart Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Patrice Desvigne-Nickens
role: STUDY_DIRECTOR
affiliation: Columbia University
name: Yoshifumi Naka, MD
role: STUDY_CHAIR
affiliation: Icahn School of Medicine at Mount Sinai
name: Annetine Gelijns, PhD
role: PRINCIPAL_INVESTIGATOR
References: