Clinical trial NCT02464969: Apixaban for the Acute Treatment of Venous Thromboembolism in Children
Official title: A Randomized, Open-Label, Active Controlled, Safety and Descriptive Efficacy Study in Pediatric Subjects Requiring Anticoagulation for the Treatment of a Venous Thromboembolic Event
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Venous Thromboembolism
Keywords: VTE, thromboembolism, thrombosis, embolism, apixaban, Eliquis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2015-06-08
Enrollment: 229
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety and descriptive efficacy of apixaban in pediatric subjects requiring anticoagulation for the treatment of a VTE.


Eligibility criteria: Inclusion Criteria:

1. Birth to \<18 years of age with a minimum weight of 2.6 kg at the time of randomization.
2. Presence of an index VTE which is confirmed by imaging.
3. Intention to manage the index VTE with anticoagulation treatment for at least 6 to 12 weeks.
4. Subjects able to tolerate oral feeding, nasogastric (NG), gastric (G) feeding and are currently tolerating enteric medications, as per investigator's judgement.

Exclusion Criteria:

1. Anticoagulant treatment for the index VTE for greater than 14 days prior to randomization. Neonates that are enrolled into the PK cohort must be on a minimum of 5 days and a maximum of 14 days SOC anticoagulation prior to randomization. Neonates that are enrolled into the post PK cohort may receive SOC anticoagulation for up to 14 days prior to randomization.
2. Thrombectomy, thrombolytic therapy, or insertion of a caval filter to treat the index VTE.
3. A mechanical heart valve.
4. Active bleeding or high risk of bleeding at the time of randomization.
5. Intracranial bleed, including intraventricular hemorrhage, within 3 months prior to randomization.
6. Abnormal baseline liver function at randomization.
7. Inadequate renal function at the time of randomization.
8. Platelet count \<50×109 per L at randomization.
9. Uncontrolled severe hypertension at the time of randomization.
10. Use of prohibited concomitant medication at the time of randomization.
11. Female subjects who are either pregnant or breastfeeding a child.
12. Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment.
13. Unable to take oral or enteric medication via the NG or G tube.
14. Known inherited or acquired antiphospholipid syndrome (APS).
15. Known inherited bleeding disorder or coagulopathy with increased bleeding risk (eg, hemophilia, von Willebrand disease, etc.)

Primary outcomes:
measure: Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding
timeFrame: From first dose (Day 1) up to 114 days
measure: Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality
timeFrame: From first dose (Day 1) up to 114 days
Secondary outcomes:
measure: Percentage of Participants Who Died
timeFrame: From first dose (Day 1) up to 114 days
measure: Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality
timeFrame: From first dose (Day 1) up to 114 days
measure: Number of Participants With Index Venous Thromboembolism (VTE) Status
timeFrame: From first dose (Day 1) up to 91 days
measure: Percentage of Participants With Stroke
timeFrame: From first dose (Day 1) up to 114 days
measure: Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE)
timeFrame: From first dose (Day 1) up to 114 days
measure: Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE)
timeFrame: From first dose (Day 1) up to 114 days
measure: Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE)
timeFrame: From first dose (Day 1) up to 114 days
measure: Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding
timeFrame: From first dose (Day 1) up to 114 days
measure: Blood Concentration of Apixaban (ng/mL)
timeFrame: 3 hour (H), 12 H, 24 H at Day 3; pre and post dose at Day 14 and Day 42
measure: Concentration of Plasma Anti-Factor Xa (ng/mL)
timeFrame: Pre and post dose at Day 14 and Day 42
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pediatric Cardiology Clinic
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center Oakland
state: California
city: Palo Alto
country: United States
facility: Bass Speicalty Pharmacy
state: California
city: Palo Alto
country: United States
facility: Inpatient Pharmacy
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hosptial - Stanford University
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Bernardino
country: United States
facility: Loma Linda University Health Care
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Mission Bay Pediatric Clinical Research Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado - Investigational Drug Services
state: Colorado
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center Pharmacy
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Nemours/ Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Hollywood
country: United States
facility: JDCH Division of Pediatric Hematology and Oncology
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando-Pharmacy Investigational Drug Services
state: Florida
city: Orlando
country: United States
facility: AdventHealth Pediatric Oncology Hematology at Orlando
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Children's Hematology and Oncology a division of Kidz medical Service
state: Florida
city: West Palm Beach
country: United States
facility: St. Mary's Medical Center
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta-Egleston
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Center for Advanced Pediatrics - Pediatric Research Unit
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Center for Advanced Pediatrics-IDS Pharmacy
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Peoria
country: United States
facility: Unity Point Methodist Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: IU Health Pharmacy
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children at IU Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York-Presbyterian Morgan Stanley Children's Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Levine Children's Specialty Center
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital, Pediatric Research
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Durham
country: United States
facility: Investigational Drug Service, Duke University Hospital
state: North Carolina
city: Fargo
country: United States
facility: Sanford Children's Hospital
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: OU Medical Center Investigational Drug Pharmacy
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina: Investigational Drug Services
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital- Main Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital- Wallace Tower
state: Texas
city: San Antonio
country: United States
facility: The Children's Hospital of San Antonio
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Versiti Wisconsin
state: Wisconsin
city: Randwick
country: Australia
facility: Kids Cancer Centre
state: New South Wales
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Childrens Hospital
state: Victoria
city: Innsbruck
country: Austria
facility: A.o.Landeskrankenhaus Innsbruck
state: Tyrol
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Edmonton
country: Canada
facility: Kaye Edmonton Clinic
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Science Corporation/McMaster Children's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital For Sick Children
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Marseille
country: France
facility: Hopital de la Timone Enfants
city: Montpellier Cedex 5
country: France
facility: CHRU de Montpellier - Hopital Arnaud de Villeneuve
city: Paris
country: France
facility: Hopital Necker-Enfants malades
city: PESSAC Cedex
country: France
facility: CHU de Bordeaux - Hopital Haut-Leveque
city: PESSAC Cedex
country: France
facility: Service d'Imagerie Medicale du Pr F. Laurent
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Munchen
country: Germany
facility: Technische Universitat, Deutsches Herzzentrum Munchen
city: Jerusalem
country: Israel
facility: Hadassah Medical Center (Ein Kerem)
city: Guadalajara
country: Mexico
facility: O.P.D Hospital Civil de Guadalajara, Hospital Civil Fray Antonio Alcalde
state: Jalisco
city: Mexico City
country: Mexico
facility: Instituto Nacional De Cardiologia Ignacio Chavez
city: Kazan
country: Russian Federation
facility: State Autonomous Healthcare Institution "Children's Republican Clinical Hospital of Ministry of
state: Republic Tatarstan
city: Yekaterinburg
country: Russian Federation
facility: State Autonomous Healthcare Institution of Sverdlovsk Region
state: Sverdlovsk Region
city: Moscow
country: Russian Federation
facility: FSBI "NRMC PHOI n.a.Dmitry Rogachev" of Minzdrav Russia
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona
city: Boadilla del Monte
country: Spain
facility: Hospital Universitario HM Monteprincipe
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Seyhan
country: Turkey
facility: Adana Acibadem Hospital
state: Adana
city: Bahcelievler
country: Turkey
facility: Baskent Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari ABD Cocuk Hematoloji Onkoloji BD
state: Ankara
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children's Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital Pediatric Hematology and Oncology Clinic
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Cocuk Hastanesi Cocuk Hematoloji Bilim Dali
city: Dnipro
country: Ukraine
facility: Communal Enterprise "Dnipropetrovsk Specialized Clinical Medical Center of Mother and Child
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk Regional Children's Hospital
city: Dnipro
country: Ukraine
facility: Municipal enterprise "Dnipropetrovsk Regional Children's Clinical Hospital"
city: Zaporizhzhia
country: Ukraine
facility: Communal Institution "Zaporizhzhia Regional Clinical Children's Hospital"
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
state: Scotland
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals NHS Foundation Trust
state: Tyne & Wear
city: Cardiff
country: United Kingdom
facility: Cardiff & Vale NHS Health Board
state: Wales
city: Cardiff
country: United Kingdom
facility: Noah's Ark Children's Hospital for Wales
state: Wales
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust
state: WEST Midlands
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
state: WEST Midlands
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: