Antiplatelet Activity of Aspirin in Infants After Aortopulmonary and Cavopulmonary Shunts

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by University of Utah.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by (Responsible Party):
Dongngan Truong, University of Utah
ClinicalTrials.gov Identifier:
NCT01656993
First received: July 26, 2012
Last updated: August 29, 2012
Last verified: August 2012

July 26, 2012
August 29, 2012
October 2012
November 2013   (final data collection date for primary outcome measure)
The percentage of arachidonic acid inhibition of platelets, as measured by TEG-PM after the initiation of ASA. [ Time Frame: TEG-PM will be measured after the third dose of ASA is given postoperatively. (up to 6 months after surgery) ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01656993 on ClinicalTrials.gov Archive Site
  • The percentage of arachidonic acid inhibition of platelets, as measured by TEG-PM at the first postoperative cardiology clinic visit. [ Time Frame: The percentage of arachidonic acid inhibition will be measured at the first post-operative cardiology clinic vist (typically 2-4 weeks after hospital discharge) ] [ Designated as safety issue: No ]
  • The percentage of arachidonic acid inhibition of platelets, as measured by TEG-PM 3-6 months after surgery. [ Time Frame: TEG-PM will be measured 3-6 months postoperatively to determine the percentage of arachidonic acid inhibition. ] [ Designated as safety issue: No ]
  • The number of bleeding and thrombotic events while patients are on ASA. [ Time Frame: Patients will be monitored for bleeding and thrombotic events while on ASA for the duration of this study, thus for up to 1.5 years. ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Antiplatelet Activity of Aspirin in Infants After Aortopulmonary and Cavopulmonary Shunts
Antiplatelet Activity of Aspirin in Infants After Aortopulmonary and Cavopulmonary Shunts

Background: Blood clots cause poor outcomes, including death, in babies with heart defects that require a surgical connection ("shunt") to provide blood flow to their lungs. Aspirin (ASA) blocks the part of the blood that helps clots form (platelets). Aspirin is used in babies with shunts to prevent blood clots. The dose of aspirin given to babies is based on adult research. Because babies are different from adults, the investigators do not know if the dose is enough to block platelets, or if it is too much and may cause bleeding. The investigators can test the platelets using a blood test called Thromboelastography with Platelet Mapping (TEG-PM). This test needs a small amount of blood so it can be used in babies.

Hypothesis and Specific Aims: The investigators suspect the aspirin doses typically given babies are not enough to block platelets and prevent blood clots in their shunts. The investigators want to determine the percentage of babies whose platelets are not blocked enough (< 70% inhibition), by using TEG-PM. The investigators also want to determine how often bleeding or clots occur in babies receiving aspirin.

Background: Aortopulmonary and cavopulmonary shunts ("shunts") are surgically placed to provide pulmonary blood flow in infants with congenital heart disease who require the shunt for survival. Thrombosis occurs in about 17% of these shunted infants (Li et al, 2007; Monagle et al, 2012) with an associated morbidity of 23% and mortality of 7%.(Li et al, 2007) One study reported a third of all deaths were from shunt thrombosis.(Fenton, 2003) Despite insufficient evidence to guide appropriate dosing, current thromboprophylaxis guidelines recommend aspirin (ASA) for thrombus prevention in these high-risk infants. No therapeutic monitoring exists to ensure consistent and effective anticoagulation and prevent over-anticoagulation to minimize bleeding complications. Previous studies examining the effectiveness of ASA in shunt thrombosis prevention have conflicting results. The most recent large, prospective observational study showed a significant association between ASA use and lower risk of thrombosis and death (Li et al, 2007), but the study was limited by lack of standardized ASA dosing and failure to include adverse events. To further complicate the picture, adult studies have described a phenomenon termed "ASA resistance," where thrombosis occurs despite ASA therapy.(Frelinger et al, 2008; Heistein et al, 2008; Szczeklik et al, 2005; Frelinger et al, 2006) ASA resistance has not been adequately studied in the pediatric population leading to a knowledge gap between therapeutic dosing and the adequate prevention of thrombosis combined with minimization of bleeding complications. Thromboelastography with Platelet Mapping (TEG-PM) is a blood test that specifically evaluates the percentage of inhibition of the arachidonic acid pathway targeted by ASA. It can be used for serial monitoring of the adequacy of anticoagulation with ASA in shunted infants and to provide evidence of safe and effective dosages for its use in other pediatric populations. 

Hypothesis and Specific Aims:

Hypothesis: The investigators hypothesize that ASA dosing by current guidelines (1-5 mg/kg/day) favors protection from bleeding complications and fails to achieve adequate inhibition of the arachidonic acid pathway to prevent thrombosis.

Specific Aim 1: The primary aim is to determine the percentage of infants treated with ASA after shunt surgery who have adequate (> 70%) inhibition of the arachidonic acid pathway as measured by TEG-PM.

Outcome: The percentage of arachidonic inhibition, as measured by TEG-PM, at 3 designated time points after starting ASA postoperatively. Therefore, TEG-PM will be measured at these designated time points:

  1. After the third dose of ASA
  2. At the first post-operative cardiology clinic visit (between 2 and 4 weeks after hospital discharge)
  3. At a follow-up cardiology clinic visit 3-6 months after the initiation of ASA

Specific Aim 2: The secondary aim is to describe the frequency of bleeding and thrombotic events while on ASA.

Outcome: The number of bleeding and thrombotic events from initiation of ASA therapy to end of study will be documented.

ASA administration: ASA will be initiated by the cardiac intensive care unit attending physician postoperatively, at a dose of 1-5 mg/kg/day, but no less than 20 mg per day; the initiation of ASA at 1-5 mg/kg/day is standard of care and recommended by the College of Chest Physicians (Monagle et al, 2012), albeit with limited evidence for its use. TEG-PM results obtained for research purposes will be available only to the research team. The dose of ASA will not be adjusted by results from the research TEG-PM. However, if bleeding or thrombosis occurs, TEG-PM is obtained by local practice and ASA dosing adjusted by the treating physician. If the dose of ASA is changed while the patient is hospitalized, TEG-PM will be obtained 2 hours after the third (adjusted or restarted) dose.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample

Infants undergoing cardiac surgery involving aortopulmonary and/or cavopulmonary shunts with planned aspirin treatment

Congenital Heart Disease
Not Provided
ASA activity
Participants (age 2.0 days to 12 months) undergoing cardiac surgery for a shunt and planned treatment with aspirin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
45
April 2014
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Undergoing cardiac surgery for a shunt and planned treatment with aspirin
  • Age 2.0 days to 12 months
  • Consent of parent or guardian

Exclusion Criteria:

  • Known or suspected congenital or acquired coagulation disorders (such as hemophilia, von Willebrands disease, Glansmans thrombasthenia).
  • History of aspirin use within 7 days of surgery.
  • Platelet count < 50K prior to surgery.
  • Weight < 2.5 kg.
  • Prematurity defined as gestational age < 37 weeks.
Both
up to 12 Months
No
Contact: Dongngan Truong, MD 801.662.5497 dongngan.truong@imail.org
United States
 
NCT01656993
55107
Yes
Dongngan Truong, University of Utah
University of Utah
Not Provided
Principal Investigator: Dongngan Truong, MD University of Utah / Primary Children's Medical Center
University of Utah
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP