Clinical Assessment of Thrombosis in Children After Heart Surgery (CATCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by The Hospital for Sick Children
Sponsor:
Information provided by (Responsible Party):
Brian McCrindle, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT01435473
First received: September 8, 2011
Last updated: August 25, 2013
Last verified: August 2013
  Purpose

Thromboembolic complications (TCs) are important causes of morbidity and mortality after pediatric cardiac surgery, resulting in longer hospital stay, increased risk of early and late post-surgical complications, early reoperation, neurologic and organ damage, and potentially death. The true incidence of blood clots in pediatric surgical patients is unknown.

The overarching objective of this study is to further our understanding of TCs, including quantification, characterization and risk stratification. This study will ultimately allow the development of effective tools for prevention and early identification of TCs, rather than focusing on treatment alone.


Condition Intervention
Thrombosis
Procedure: Cardiac Surgery

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical Assessment of Thrombosis in Children After Heart Surgery: The CATCH Study

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Incidence of Thromboembolic Complications (TC) after pediatric cardiac surgery [ Time Frame: Outcome will be recorded throughout the duration of the participants hospital stay, an expected average of 10 days ] [ Designated as safety issue: No ]
    Thrombosis will be recorded through review of post-operative clinical assessments, targeted laboratory testing for blood abnormalities and echocardiographic/ultrasound evaluation.


Secondary Outcome Measures:
  • Assessment of the patients' coagulation, hemostatic and inflammatory system activity [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Standard coagulation panel to assess the function of the coagulation system in order to identify the degree of maturity, potential for resistance to anticoagulation and overall activity of the coagulation system.

  • Genome-Wide Association Study (GWAS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    To identify genetic polymorphisms associated with coagulation system activity, sensitivity and overall thrombotic risk.

  • Post-operative sign and symptoms of thrombosis [ Time Frame: Up to 10 days after surgery ] [ Designated as safety issue: No ]
    Daily clinical assessment of signs and symptoms of thrombosis

  • Post-thrombotic Syndrome (PTS) Evaluation [ Time Frame: Up to 2 years after surgery ] [ Designated as safety issue: No ]
    Assessment of upper and lower limbs based on the adaptation of the Khule scale. PTS will be classified as mild, moderate and severe.

  • Neurodevelopment and functional health assessment [ Time Frame: Up to 2 years post- surgery ] [ Designated as safety issue: No ]
    Subject will undergo Ages and Stages (ASQ, Child Health Questionnaires and PedsQL)

  • Response of the patients coagulation, hemostatic and inflammatory system activity to cardiopulmonary bypass [ Time Frame: Up to 10 days after surgery ] [ Designated as safety issue: No ]
    Repeat of complete blood count, inflammatory markers, coagulation and fibrolnolytic systems activity

  • Proportion of patients with thrombo-occlusive complications of thrombosis [ Time Frame: 18-24 months after surgery ] [ Designated as safety issue: No ]

    Following events associated with thrombosis:

    • Death / cardiorespiratory arrest associated with thrombosis
    • Embolism (cardioembolic stroke, pulmonary embolism)
    • Obstruction (sinovenous stroke, SVC syndrome)
    • Unanticipated procedures directed at thrombosis or its clinical impact
    • Escalation of antithrombotic treatment


Estimated Enrollment: 500
Study Start Date: July 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Children undergoing heart surgery
The study will follow children undergoing cardiac surgery at The Hospital for Sick Children from pre-consultation, throughout surgery, recovery and post-operative follow-up
Procedure: Cardiac Surgery

Detailed Description:

There is very limited data on TCs associated with cardiac surgery in pediatric patients. The actual incidence of TCs in this context is not currently known reflecting a lack of clinical suspicion, reporting biases, and/or the use of inappropriate diagnostic tests

Pediatric cardiac surgery is associated with disruption of blood flow, platelet dysfunction and activation, and blood hypercoagulability; all of which are contributing to clot formation

All congenital heart defects are associated with blood flow disturbance but some are associated with more extreme disturbances. The investigators hypothesize that not all types of CHD repairs will be at the same risk of TCs based on the extent of blood flow disturbances they cause. The investigators hypothesize that line location, difficulties in line insertion, including multiple insertion attempts and longer duration of indwelling will be associated with increased risk of TCs.

Pediatric cardiac surgery is associated with inflammation and platelet activation, both of which are potent contributors to blood hypercoagulability: CPB presents a hemostatic challenge associated with an abundance of pro-thrombotic risk factors and an opposite presence of pro-hemorrhagic risk factors. The investigators hypothesize that factors associated with increased platelet activation and inflammation, and in consequence, greater laboratory values of markers of platelet activation and inflammation, will be associated with increased risk of TCs.

Coagulation system activity in children is immature, hyporeactive and exhibits a high degree of resistance to heparin and anticoagulation. The investigators theorize that lower levels of coagulation system activity, presence of high-risk genetic polymorphisms, greater CPB hemodilution, increased heparin requirement and lower blood heparin activity expressed by anti-factor X activity (anti-Xa) concentration during CPB and greater requirement for allogeneic blood will be associated for increased risk of TCs.

There is a lack of consensus on clinical and laboratory signs/symptoms of active thrombosis and on which patients should be routinely screened for TCs. One of the most difficult aspects in the management of TCs is the fact that many episodes are asymptomatic or have non-specific symptoms. Creating a risk stratification model including both clinical and laboratory abnormalities which could be indicative of TCs in the post-operative period in order to identify patients who should undergo more targeted screening is the third aim of this study.

Many methods of TC management have limited effectiveness while highly effective methods are often associated with much risk. The use of thrombolytics in children is rare and only partially effective in many cases. The margin of safety for treatment is thought to be very narrow; the reported frequency of major bleeding episodes varies from 5% to 40%.

Outcomes of TCs are suboptimal, early surgical and long-term complications for survivors are frequent. The creation of risk stratification models for suboptimal surgical outcomes, PTS syndrome and, lower functional health status after surgery will be the fourth and final aim of this study.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Children Undergoing Pediatric Heart Surgery at the Hospital for Sick Children who agree to participate in the CATCH research study.

Criteria

Inclusion Criteria:

  • Pediatric patients scheduled for cardiac surgery requiring cardiopulmonary Bypass

Exclusion Criteria:

  • Known severe risk factors to thromboembolic complications
  • Active cancer
  • Congenital coagulopathy (e.g. haemophilia)
  • No planned cardiology follow-up at the Hospital for Sick Children
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435473

Contacts
Contact: Cedric Manlhiot 416-813-7617 cedric.manlhiot@sickkids.ca

Locations
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Cedric Manlhiot    416-813-7617    cedric.manlhiot@sickkids.ca   
Contact: Brian W McCrindle    416-813-7610    brian.mccrindle@sickkids.ca   
Principal Investigator: Brian W Manlhiot, MD         
Sub-Investigator: Cedric Manlhiot         
Sub-Investigator: Colleen E Gruenwald         
Sub-Investigator: Leonardo R Brandao         
Sub-Investigator: Luc Mertens         
Sub-Investigator: Seema Mital         
Sub-Investigator: Leland N Benson         
Sub-Investigator: Christopher A Calderone         
Sub-Investigator: Helen M Holtby         
Sub-Investigator: Jennifer Russell         
Sub-Investigator: Ben V Sivarajan         
Sub-Investigator: Glen Van Arsdell         
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Brian W McCrindle, MD The Hospital for Sick Children, Toronto Canada
  More Information

No publications provided

Responsible Party: Brian McCrindle, Staff Cardiologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01435473     History of Changes
Other Study ID Numbers: 1000020203
Study First Received: September 8, 2011
Last Updated: August 25, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by The Hospital for Sick Children:
pediatrics
thrombosis
thromboembolic complications
pediatric cardiac surgery

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 18, 2014