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

NCT02981472 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CV185-3622016-001247-39
• Study Type: interventional
• Target: 192
• Locations: 13 countries
• Sites: 45

Brief Summary

To investigate the safety and pharmacokinetics of apixaban in children with congenital or acquired heart disease who have a need for anticoagulation.

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (1)

• Composite of Adjudicated Major or Clinically Relevant Non-Major (CRNM) Bleeding Events

  The number of participants with adjudicated major or CRNM bleeding events per the Perinatal and Paediatric Haemostasis Subcommittee of International Society on Thrombosis and Haemostasis (ISTH) criteria. Events are adjudicated by a blinded, independent events adjudication committee (EAC). Major bleeding 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 (i.e., 2 g/dL) in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the CNS, or bleeding that requires surgical intervention in an operating suite, including interventional radiology. CRNM bleeding satisfies one or both of the following criteria: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition or bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating room.

  From first dose to 2 days after last dose (Up to approximately 12 months)

Secondary Outcomes (14)

• The Number of Participants With Thrombotic Events and Thromboembolic Event-Related Death

  From randomization to 2 days after last dose (Up to approximately 12 months)

• The Number of Participants With Adjudicated Major Bleeding

  From first dose to 2 days after last dose (Up to approximately 12 months)

• The Number of Participants With Adjudicated CRNM Bleeding

  From first dose to 2 days after last dose (Up to approximately 12 months)

• The Number of Participants With All Adjudicated Bleeding

  From first dose to 2 days after last dose (Up to approximately 12 months)

• The Number of Participants With Drug Discontinuation Due to Adverse Effects, Intolerability, or Bleeding

  From first dose to 2 days after last dose (Up to approximately 12 months)

Study Arms (2)

Apixaban

EXPERIMENTAL

Drug: Apixaban

LMWH/VKA

ACTIVE COMPARATOR

Drug: Vitamin K Antagonist (VKA); Drug: Low Molecular Weight Heparin (LMWH)

Interventions

Apixaban DRUG

Specified dose on specified days

Also known as: Eliquis

Apixaban

Vitamin K Antagonist (VKA) DRUG

Specified dose on specified days

Also known as: Warfarin

LMWH/VKA

Low Molecular Weight Heparin (LMWH) DRUG

Specified dose on specified days

Also known as: Enoxaparin

LMWH/VKA

Eligibility Criteria

• Age: 28 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males and Females, 28 days to \< 18 years of age, inclusive
• 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 participants 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 \[eg, by mouth, nasogastric tube, or gastric tube\]
• Participants 28 days to \< 3 months must be able to tolerate oral/nasogastric tube (NGT)/gastric tube (GT) feeds for at least 5 days prior to randomization

You may not qualify if:

• Recent thromboembolic events less than 6 months prior to enrollment
• Weight \< 3 kg
• Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment
• Artificial 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
• Confirmed diagnosis of a GI ulcer
• Known antiphospholipid syndrome (APS).

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Pediatric Heart Network: collaborator
• Pfizer: collaborator

Study Sites (46)

Phoenix Children'S Hospital

Phoenix, Arizona, 85016, United States

Location

University Of California San Diego

La Jolla, California, 92093-0641, United States

Location

Children'S Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Childrens Healthcare Of Atlanta

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0008

Indianapolis, Indiana, 46202, United States

Location

Local Institution - 0009

Boston, Massachusetts, 02115, United States

Location

Local Institution - 0013

Ann Arbor, Michigan, 48109, United States

Location

Childrens Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Local Institution - 0006

Cincinnati, Ohio, 45229, United States

Location

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0012

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0011

Houston, Texas, 77030-2399, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Local Institution - 0055

Seattle, Washington, 98105, United States

Location

Local Institution

CABA, Buenos Aires, 1426, Argentina

Location

Local Institution - 0030

Parkville, Victoria, 3052, Australia

Location

Local Institution - 0001

Vienna, 1090, Austria

Location

Local Institution - 0022

Curitiba, Paraná, 80250-060, Brazil

Location

Instituto De Cardiologia Do Rio Grande Do Sul

Porto Alegre, Rio Grande do Sul, 90620-001, Brazil

Location

Local Institution - 0020

Campinas, São Paulo, 13060-080, Brazil

Location

Instituto de Pesquisa PENSI

São Paulo, 01227-200, Brazil

Location

Universidade Federal De Sao Paulo

São Paulo, 04024-002, Brazil

Location

Local Institution - 0015

Toronto, Ontario, M5G 1X8, Canada

Location

Local Institution - 0031

HUS, 00029, Finland

Location

Local Institution - 0002

Freiburg im Breisgau, 79106, Germany

Location

Local Institution - 0004

Hamburg, 20246, Germany

Location

Local Institution - 0003

München, 80636, Germany

Location

Local Institution - 0047

Petah Tikva, 0, Israel

Location

Local Institution - 0046

Tel Litwinsky, 52620, Israel

Location

Local Institution - 0026

Rome, Roma, 00165, Italy

Location

Local Institution - 0028

Bologna, 40138, Italy

Location

Local Institution - 0027

Milan, 20097, Italy

Location

Local Institution - 0044

León, Guanajuato, 37000, Mexico

Location

Local Institution - 0018

Mexico City, Mexico City, 04530, Mexico

Location

Local Institution - 0019

Mexico City, Mexico City, 06720, Mexico

Location

Local Institution - 0016

Mexico City, Mexico City, 14080, Mexico

Location

Local Institution

Kazan', 420012, Russia

Location

Local Institution

Kemerovo, 650002, Russia

Location

Local Institution - 0057

Novosibirsk, 630055, Russia

Location

Local Institution - 0062

Yekaterinburg, 620134, Russia

Location

Local Institution - 0049

Barcelona, 08950, Spain

Location

Local Institution

Madrid, 28007, Spain

Location

Local Institution - 0048

Madrid, 28046, Spain

Location

Local Institution - 0040

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Local Institution - 0042

Bristol, Somerset, BS2 8BJ, United Kingdom

Location

Local Institution

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Payne RM, Burns KM, Glatz AC, Male C, Donti A, Brandao LR, Balling G, VanderPluym CJ, Bu'Lock F, Kochilas LK, Stiller B, Cnota JF 2nd, Rahkonen O, Khan A, Adorisio R, Stoica S, May L, Burns JC, Saraiva JFK, McHugh KE, Kim JS, Rubio A, Chia-Vazquez NG, Meador MR, Dyme JL, Reedy AM, Ajavon-Hartmann T, Jarugula P, Carlson-Taneja LE, Mills D, Wheaton O, Monagle P. Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease. J Am Coll Cardiol. 2023 Dec 12;82(24):2296-2309. doi: 10.1016/j.jacc.2023.10.010.

  PMID: 38057072 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Thrombosis

Interventions

apixaban; acarboxyprothrombin; Warfarin; Heparin, Low-Molecular-Weight; Enoxaparin

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: December 5, 2016
• Study Start: January 19, 2017
• Primary Completion: October 18, 2021
• Study Completion: October 18, 2021
• Last Updated: October 3, 2022
• Results First Posted: May 18, 2022

Record last verified: 2022-09

Locations

BR (5); AU (1); FI (1); DE (3); IL (2); IT (3); RU (4); GB (3); ME (4); ES (3); CA (1); AR (1); US (14)