Ignite Creation Date:
2024-05-06 @ 12:31 AM
Last Modification Date:
2024-10-26 @ 10:51 AM
Study NCT ID:
NCT01598883
Status:
COMPLETED
Last Update Posted:
2016-12-14
First Post:
2012-04-24
Brief Title:
Understanding Heparin Resistance in Cardiac Surgery
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
Understanding Heparin Resistance in Cardiac Surgery Altered Heparin Responsiveness and Its Association With Acute Inflammatory Reactions
Status:
COMPLETED
Status Verified Date:
2016-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will explore altered heparin responsiveness AHR in cardiac surgical patients undergoing cardiopulmonary bypass CPB requiring systemic anticoagulation with heparin The investigators will evaluate the hypothesis that AHR may be directly related to modulated or mediated by interactions between heparin antithrombin AT the heparin-AT complex and one or more acute phase proteins The investigators are particularly interested in identifying patients with true heparin resistance that is patients who demonstrate AHR even after antithrombin-replenishment in the presence of an adequate systemic dose of heparin
Detailed Description:
This study uses a prospective randomized open-label cross-over design to evaluate the responses to recombinant human AT rhAT andor supplemental heparin for restoration of heparin-responsiveness in the presence of biomarkers of acute inflammation so called acute phase reactants Our ultimate goal is of course to apply this knowledge to optimize perioperative management of anticoagulation in patients undergoing cardiopulmonary bypass
We will first identify enrolled patients with altered heparin responsiveness AHR as defined by an ACT 450 seconds the MGH standard target ACT after the initial dose of heparin for CPB Patients who achieve an ACT 450 sec will not enter the randomization phase of the study their participation in the study will be complete and their routine clinical care will continue unaltered Those with AHR post-heparin ACT 450 sec will be randomized to receive either supplemental heparin or supplemental AT Those that fail to achieve an adequate ACT after the first supplementation will cross-over to receive the alternate supplement Blood samples totaling at most 20 ml will be taken at each step to measure heparin level AT level AT activity Once a patient is placed onto cardiopulmonary bypass their participation in the study will be complete
By design this study replicates routine clinical management of heparin anticoagulation for cardiopulmonary bypass at the MGH Most patients 80 coming to cardiac surgery who will undergo CPB respond adequately to a routine initial bolus dose of heparin ACT 450 after 350 Ukg as noted subjects in this study that achieve the target ACT will be managed according to routine clinical practice without further testing or intervention
Under routine care patients with an inadequate initial response to heparin receive either supplemental heparin 150 Ukg or pooled human antithrombin 1000 Units or both In this study subjects with inadequate heparin response ACT 450 after the initial heparin bolus will be randomly assigned to two comparison groups half will receive supplemental heparin 150 Ukg and half will receive AT 1000 IU Subjects who fail to respond to their assigned first intervention will cross-over to receive the alternate intervention
Some subjects may not achieve the target ACT despite receiving both supplemental heparin and AT comprising a group of patients with true heparin resistance whose coagulation profiles can be further characterized to better understand the mechanisms of the resistance These subjects will be considered to have completed the study even though they are not yet on cardiopulmonary bypass and will be managed according to the best clinical judgment of their physicians They may receive additional heparin additional AT fresh-frozen plasma or any combination of these These patients may be at risk for thrombotic complications during the post-operative period Accordingly when clinically appropriate these individuals may be referred for further evaluation of their coagulation status but these evaluations will not be done as part of this study
This is a pathophysiological risk-factor association study that seeks to better understand the phenomenon of altered heparin responsiveness Accordingly there is no specific study endpoint apart from achieving an ACT of 450 sec In all enrolled subjects we will measure the levels of three acute phase reactants Factor VIII fibrinogen and CRP heparin levels anti Xa AT level immunofixation and AT activity after the initial heparin dose For all subjects who do not achieve and ACT of 450 we will also measure additional heparin levels anti Xa AT level immunofixation and AT activity after each intervention in the randomizationcrossover phase The total amount of blood taken for the research-specific laboratory test is less than 20 ml
We will first identify enrolled patients with altered heparin responsiveness AHR as defined by an ACT 450 seconds the MGH standard target ACT after the initial dose of heparin for CPB Patients who achieve an ACT 450 sec will not enter the randomization phase of the study their participation in the study will be complete and their routine clinical care will continue unaltered Those with AHR post-heparin ACT 450 sec will be randomized to receive either supplemental heparin or supplemental AT Those that fail to achieve an adequate ACT after the first supplementation will cross-over to receive the alternate supplement Blood samples totaling at most 20 ml will be taken at each step to measure heparin level AT level AT activity Once a patient is placed onto cardiopulmonary bypass their participation in the study will be complete
By design this study replicates routine clinical management of heparin anticoagulation for cardiopulmonary bypass at the MGH Most patients 80 coming to cardiac surgery who will undergo CPB respond adequately to a routine initial bolus dose of heparin ACT 450 after 350 Ukg as noted subjects in this study that achieve the target ACT will be managed according to routine clinical practice without further testing or intervention
Under routine care patients with an inadequate initial response to heparin receive either supplemental heparin 150 Ukg or pooled human antithrombin 1000 Units or both In this study subjects with inadequate heparin response ACT 450 after the initial heparin bolus will be randomly assigned to two comparison groups half will receive supplemental heparin 150 Ukg and half will receive AT 1000 IU Subjects who fail to respond to their assigned first intervention will cross-over to receive the alternate intervention
Some subjects may not achieve the target ACT despite receiving both supplemental heparin and AT comprising a group of patients with true heparin resistance whose coagulation profiles can be further characterized to better understand the mechanisms of the resistance These subjects will be considered to have completed the study even though they are not yet on cardiopulmonary bypass and will be managed according to the best clinical judgment of their physicians They may receive additional heparin additional AT fresh-frozen plasma or any combination of these These patients may be at risk for thrombotic complications during the post-operative period Accordingly when clinically appropriate these individuals may be referred for further evaluation of their coagulation status but these evaluations will not be done as part of this study
This is a pathophysiological risk-factor association study that seeks to better understand the phenomenon of altered heparin responsiveness Accordingly there is no specific study endpoint apart from achieving an ACT of 450 sec In all enrolled subjects we will measure the levels of three acute phase reactants Factor VIII fibrinogen and CRP heparin levels anti Xa AT level immunofixation and AT activity after the initial heparin dose For all subjects who do not achieve and ACT of 450 we will also measure additional heparin levels anti Xa AT level immunofixation and AT activity after each intervention in the randomizationcrossover phase The total amount of blood taken for the research-specific laboratory test is less than 20 ml
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None