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A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist (VKA) or Low Molecular Weight Heparin (LMWH) in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation

This study is currently recruiting participants.
Verified December 2017 by Bristol-Myers Squibb
Sponsor:
ClinicalTrials.gov Identifier:
NCT02981472
First Posted: December 5, 2016
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Pediatric Heart Network
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb
  Purpose
To investigate the safety and pharmacokinetics of apixaban in children with congenital or acquired heart disease who have a need for anticoagulation.

Condition Intervention Phase
Thrombosis Drug: Apixaban Drug: Vitamin K Antagonist (VKA) Drug: Low Molecular Weight Heparin (LMWH) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open Label, Multi-center Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist or LMWH in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Chronic Anticoagulation for Thromboembolism Prevention

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • A composite of adjudicated major or clinically relevant non-major (CRNM) bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria [ Time Frame: 14 months ]

    Major bleeding is defined as bleeding that satisfies one or more of the following criteria:

    • fatal bleeding
    • clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L (ie, 2 g/dL) in a 24 hour period
    • bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the central nervous system
    • bleeding that requires surgical intervention in an operating suite, including interventional radiology

    CRNM bleeding is defined as bleeding which satisfies one or both of the following criteria:

    • overt bleeding for which blood product is administered and that is not directly attributable to the subject's underlying medical condition
    • bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room


Secondary Outcome Measures:
  • Apparent total body clearance [ Time Frame: 14 months ]
  • Central volume of distribution [ Time Frame: 14 months ]
  • Absorption rate constant [ Time Frame: 14 months ]
  • Cmax [ Time Frame: 14 months ]
    Maximum observed concentration

  • Cmin [ Time Frame: 14 months ]
    Trough observed concentration

  • AUC (TAU) [ Time Frame: 14 months ]
    Area under the concentration-time curve in one dosing interval

  • Factor X activity measured using chromogenic assay [ Time Frame: 14 months ]
  • Anti-FXa (Anti-factor 10a) activity measured using chromogenic assay [ Time Frame: 14 months ]
  • Exposure-response (E-R) relationships [ Time Frame: 14 months ]
  • Any thromboembolic events detected by imaging or clinical diagnosis [ Time Frame: 14 months ]
    Thromboembolic events include but are not limited to: intra-cardiac, shunt, inside Fontan pathway, pulmonary embolism (PE), stroke, other venous or arterial thromboembolic events

  • Thromboembolic event-related death [ Time Frame: 14 months ]
  • Patient/proxy reported outcome or quality of life determined by The Pediatric Quality of Life Inventory (PedsQL) generic core and cardiac modules [ Time Frame: 14 months ]
  • Patient/proxy reported outcome or quality of life determined by the Kids Informed Decrease Complications Learning on Thrombosis (KIDCLOT©) pediatric quality of life inventory [ Time Frame: 14 months ]
  • Adjudicated major bleeding [ Time Frame: 14 months ]
  • Adjudicated CRNM bleeding [ Time Frame: 14 months ]
  • All bleeding [ Time Frame: 14 months ]
    This includes minor bleeding, which is defined as any overt or macroscopic evidence of bleeding that does not fulfill the criteria for either major bleeding or CRNM bleeding

  • Drug discontinuation [ Time Frame: 14 months ]
    Can be due to adverse effects, intolerability, or bleeding

  • All causes of death [ Time Frame: 14 months ]

Estimated Enrollment: 150
Actual Study Start Date: January 4, 2017
Estimated Study Completion Date: September 30, 2020
Estimated Primary Completion Date: September 29, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apixaban

Children aged 2 to < 18 years of age randomized to the apixaban arm of the study weighing less than 35 kg will be administered apixaban 0.14 mg/kg twice daily (BID) with the 0.4 mg/ml oral solution.

Children aged 2 to < 18 years of age randomized to the apixaban arm of the study weighing greater than or equal to 35 kg will be administered apixaban 5 mg BID as a tablet. Children randomized to the apixaban arm of the study weighing greater than or equal to 35 kg who cannot swallow the tablet or prefer to take the solution will receive 12.5 ml of the 0.4 mg/ml oral solution BID.

The apixaban solution (0.4 mg/mL) or tablets (5 mg) will be administered BID orally or by nasogastric/gastric tube at a fixed dose, with no monitoring of international normalized ratio (INR) or anti-Xa level required to adjust dose.

Drug: Apixaban
Oral solution or tablet
Other Name: Eliquis
Active Comparator: LMWH/VKA
The standard-of-care (SOC), vitamin K antagonist (VKA), or subcutaneous low molecular weight heparin (LMWH) will comprise the active comparator group. VKA or LMWH will either be commercial products labeled as per country requirements and provided by Bristol-Myers Squibb or sourced locally according to the SOC. Dose regimen and monitoring for VKA (including INR control) and LMWH will follow the American College of Chest Physicians (ACCP) 2012 guideline for thromboembolism (TE) prophylaxis.
Drug: Vitamin K Antagonist (VKA)
1, 2.5, and 5 mg
Other Name: Warfarin
Drug: Low Molecular Weight Heparin (LMWH)
100mg/mL
Other Name: Enoxaparin

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   34 Weeks to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Males and females, 34 weeks adjusted gestational age to < 18 years of age
  • Congenital or acquired heart diseases requiring chronic anticoagulation for thromboprophylaxis (eg, single ventricle physiology including all 3 stages of palliation, dilated cardiomyopathy, Kawasaki disease with coronary aneurysms, and pulmonary hypertension)
  • Eligible patients include those who newly start anticoagulants and those who are currently on VKA or LMWH or other anticoagulants for thromboprophylaxis
  • Able to tolerate enteral medication [eg, by mouth, nasogastric tube, or gastric tube]

Exclusion Criteria:

  • Recent thromboembolic events less than 6 months prior to enrollment
  • Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment
  • Prosthetic heart valves and mechanical heart valves
  • Known inherited bleeding disorder or coagulopathy (e.g. hemophilia, von Willebrand disease, etc.)
  • Active bleeding at the time of enrollment
  • Any major bleeding other than perioperative in the preceding 3 months
  • Known intracranial congenital vascular malformation or tumor

Other protocol defined inclusion/exclusion criteria could apply

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02981472


Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 46 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Pediatric Heart Network
Pfizer
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02981472     History of Changes
Other Study ID Numbers: CV185-362
2016-001247-39 ( EudraCT Number )
First Submitted: November 18, 2016
First Posted: December 5, 2016
Last Update Posted: December 7, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Heart Diseases
Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Vascular Diseases
Vitamins
Vitamin K
Calcium heparin
Apixaban
Heparin
Heparin, Low-Molecular-Weight
Dalteparin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antifibrinolytic Agents
Hemostatics
Coagulants