Venous ThromboembolismPhase 4NCT02464969
Apixaban for the Acute Treatment of Venous Thromboembolism in Children
A Phase 4 study testing Apixaban in people with Venous Thromboembolism, run by Bristol-Myers Squibb at 128 sites in 13 countries.
Trial summary
To assess the safety and descriptive efficacy of apixaban in pediatric subjects requiring anticoagulation for the treatment of a VTE. Read more about this study
- Who is it for?
- Ages 0 days to 17 years
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Apixaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 229 participants
- Where
- 128 sitesin 13 countries
- Study dates
- 22 Nov 2015to 30 Apr 2024
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Birth to <18 years of age with a minimum weight of 2.6 kg at the time of randomization.
- Presence of an index VTE which is confirmed by imaging.
- Intention to manage the index VTE with anticoagulation treatment for at least 6 to 12 weeks.
- Subjects able to tolerate oral feeding, nasogastric (NG), gastric (G) feeding and are currently tolerating enteric medications, as per investigator's judgement.
Who cannot join
- 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.
- Thrombectomy, thrombolytic therapy, or insertion of a caval filter to treat the index VTE.
- A mechanical heart valve.
- Active bleeding or high risk of bleeding at the time of randomization.
- Intracranial bleed, including intraventricular hemorrhage, within 3 months prior to randomization.
- Abnormal baseline liver function at randomization.
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- Inadequate renal function at the time of randomization.
- Platelet count <50×109 per L at randomization.
- Uncontrolled severe hypertension at the time of randomization.
- Use of prohibited concomitant medication at the time of randomization.
- Female subjects who are either pregnant or breastfeeding a child.
- Use of aggressive life-saving therapies such as ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) at the time of enrollment.
- Unable to take oral or enteric medication via the NG or G tube.
- Known inherited or acquired antiphospholipid syndrome (APS).
- Known inherited bleeding disorder or coagulopathy with increased bleeding risk (eg, hemophilia, von Willebrand disease, etc.)
Trial locations and contacts
128 sites in 13 countries.
128 sites in 13 countries
United States84 sites
Akron Children's Hospital
Akron, Ohio, 44308
University of Michigan
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta-Egleston
Atlanta, Georgia, 30322
Children's Healthcare of Atlanta Center for Advanced Pediatrics - Pediatric Research Unit
Atlanta, Georgia, 30329
Children's Healthcare of Atlanta Center for Advanced Pediatrics-IDS Pharmacy
Atlanta, Georgia, 30329
Children's Hospital Colorado - Investigational Drug Services
Aurora, Colorado, 80045
Children's Hospital Colorado
Aurora, Colorado, 80045
Pediatric Cardiology Clinic
Birmingham, Alabama, 35233
University of Alabama
Birmingham, Alabama, 35233
Boston Children's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina: Investigational Drug Services
Charleston, South Carolina, 29425
Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
Charleston, South Carolina, 29425
Medical University of South Carolina
Charleston, South Carolina, 29425
Levine Children's Specialty Center
Charlotte, North Carolina, 28203
Levine Children's Hospital, Pediatric Research
Charlotte, North Carolina, 28207
Levine Children's Hospital
Charlotte, North Carolina, 28207
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Investigational Drug Service, Duke University Hospital
Durham, North Carolina, 27710
Sanford Children's Hospital
Fargo, North Dakota, 58104
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
UF Health Shands Hospital
Gainesville, Florida, 32610
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center Pharmacy
Hartford, Connecticut, 06106
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
JDCH Division of Pediatric Hematology and Oncology
Hollywood, Florida, 33021
Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Memorial Regional Hospital
Hollywood, Florida, 33021
Texas Children's Hospital- Main Hospital
Houston, Texas, 77030
Texas Children's Hospital- Wallace Tower
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202-5225
IU Health Pharmacy
Indianapolis, Indiana, 46202
Riley Hospital for Children at IU Health
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's Mercy Hospital
Kansas City, Missouri, 64108
University of Kentucky Medical Center
Lexington, Kentucky, 40536
Loma Linda University Cancer Center
Loma Linda, California, 92350
Loma Linda University Children's Hospital
Loma Linda, California, 92354
Loma Linda University Medical Center
Loma Linda, California, 92354
Valley Children's Hospital
Madera, California, 93636
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Versiti Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-7610
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University Medical Center
New York, New York, 10032
New York-Presbyterian Morgan Stanley Children's Hospital
New York, New York, 10032
Children's Hospital and Research Center Oakland
Oakland, California, 94609
OU Medical Center Investigational Drug Pharmacy
Oklahoma City, Oklahoma, 73104
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
AdventHealth Orlando
Orlando, Florida, 32803
AdventHealth Orlando-Pharmacy Investigational Drug Services
Orlando, Florida, 32804
AdventHealth Pediatric Oncology Hematology at Orlando
Orlando, Florida, 32804
Bass Speicalty Pharmacy
Palo Alto, California, 94304
Inpatient Pharmacy
Palo Alto, California, 94304
Lucile Packard Children's Hosptial - Stanford University
Palo Alto, California, 94304
Bleeding and Clotting Disorders Institute
Peoria, Illinois, 61614
Unity Point Methodist Medical Center
Peoria, Illinois, 61636
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Children's Hospital
Phoenix, Arizona, 85016
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Primary Children's Hospital
Salt Lake City, Utah, 84113
The Children's Hospital of San Antonio
San Antonio, Texas, 78207
University of Texas Health San Antonio
San Antonio, Texas, 78229
Loma Linda University Health Care
San Bernardino, California, 92408
UCSF Benioff Children's Hospital
San Francisco, California, 94158
UCSF Mission Bay Pediatric Clinical Research Center
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
SUNY Upstate Medical University
Syracuse, New York, 13210
St. Joseph's Hospital
Tampa, Florida, 33607
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
Children's Hematology and Oncology a division of Kidz medical Service
West Palm Beach, Florida, 33407
St. Mary's Medical Center
West Palm Beach, Florida, 33407
Nemours/ Alfred I. duPont Hospital for Children
Wilmington, Delaware, 19803
United Kingdom6 sites
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, WEST Midlands, B4 6NH
Birmingham Women's and Children's NHS Foundation Trust
Birmingham, WEST Midlands, B4 6NH
Cardiff & Vale NHS Health Board
Cardiff, Wales, CF14 4XW
Noah's Ark Children's Hospital for Wales
Cardiff, Wales, CF14 4XW
Royal Hospital for Children
Glasgow, Scotland, G51 4TF
Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, TYNE & WEAR, NE1 4LP
Canada5 sites
Kaye Edmonton Clinic
Edmonton, Alberta, T6G 1Z1
Stollery Children's Hospital
Edmonton, Alberta, T6G 2B7
Hamilton Health Science Corporation/McMaster Children's Hospital
Hamilton, Ontario, L8N3Z5
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
The Hospital For Sick Children
Toronto, Ontario, M5G 1X8
France5 sites
Hopital de la Timone Enfants
Marseille, 13385
CHRU de Montpellier - Hopital Arnaud de Villeneuve
Montpellier, 34295
Hopital Necker-Enfants malades
Paris, 75015
CHU de Bordeaux - Hopital Haut-Leveque
Pessac, 33604
Service d'Imagerie Medicale du Pr F. Laurent
Pessac, 33604
Turkey (Türkiye)5 sites
Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children's Hospital
Ankara, 06230
Ankara City Hospital Pediatric Hematology and Oncology Clinic
Ankara, 06800
Baskent Universitesi Tip Fakultesi Cocuk Sagligi ve Hastaliklari ABD Cocuk Hematoloji Onkoloji BD
Bahçelievler, Ankara, 06490
Ege Universitesi Tip Fakultesi Cocuk Hastanesi Cocuk Hematoloji Bilim Dali
Izmir, 35100
Adana Acibadem Hospital
Seyhan, Adana, 01130
Spain4 sites
Hospital Universitario Vall d´Hebron
Barcelona, 08035
Hospital Universitario HM Monteprincipe
Boadilla del Monte, Madrid, 28660
Hospital Sant Joan de Deu
Esplugues de Llobregat, Barcelona, 08950
Hospital Universitario La Paz
Madrid, 28046
Ukraine4 sites
Communal Enterprise "Dnipropetrovsk Specialized Clinical Medical Center of Mother and Child
Dnipro, 49006
Dnipropetrovsk Regional Children's Hospital
Dnipro, 49100
Municipal enterprise "Dnipropetrovsk Regional Children's Clinical Hospital"
Dnipro, 49100
Communal Institution "Zaporizhzhia Regional Clinical Children's Hospital"
Zaporizhzhya, 69063
Australia3 sites
The Royal Childrens Hospital
Parkville, VC, 3052
Kids Cancer Centre
Randwick, New South Wales, 2031
Prince of Wales Hospital
Sydney, New South Wales, 2031
Austria3 sites
A.o.Landeskrankenhaus Innsbruck
Innsbruck, Tyrol, 6020
Medizinische Universitaet Innsbruck
Innsbruck, 6020
Medizinische Universitaet Wien
Vienna, 1090
Germany3 sites
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)
Berlin, 13353
Universitätsklinikum Essen
Essen, 45147
Technische Universitat, Deutsches Herzzentrum Munchen
München, 80636
Russia3 sites
State Autonomous Healthcare Institution "Children's Republican Clinical Hospital of Ministry of
Kazan', Republic Tatarstan, 420138
FSBI "NRMC PHOI n.a.Dmitry Rogachev" of Minzdrav Russia
Moscow, 117198
State Autonomous Healthcare Institution of Sverdlovsk Region
Yekaterinburg, Sverdlovsk Oblast, 620149
Mexico2 sites
O.P.D Hospital Civil de Guadalajara, Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, 44280
Instituto Nacional De Cardiologia Ignacio Chavez
Mexico City, 14080
About this study
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
To assess the safety and descriptive efficacy of apixaban in pediatric subjects requiring anticoagulation for the treatment of a VTE.
- Conditions
- Venous Thromboembolism
- Being tested
- Apixaban, Standard of Care
- Keywords
- VTE, thromboembolism, thrombosis, embolism, apixaban, Eliquis
- Medical subject headings
- Venous Thromboembolism, Thromboembolism, Thrombosis, Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Tablet or Solution
Standard of CareDrug
Unfractionated heparin, low molecular weight heparin, and/or a vitamin K antagonist. For subjects under 2 years of age, standard of care will be limited to unfractionated heparin or low molecular weight heparin.
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Experimental | Subjects between birth to <18 years will be dosed on a body weight tiered regimen. Subjects ≥35kg will receive 10mg twice daily(BID) for 7 days followed by 5mg BID thereafter;<35kg to 25kg will receive 8mg BID for 7 days followed by 4mg BID thereafter;<25 to 18kg will receive 6mg BID for 7 days and then 3mg BID thereafter;<18 to 12kg will receive 4mg BID for 7 days and then 2mg BID thereafter;<12 to 9kg will receive 3mg BID for 7 days and then 1.5mg BID thereafter;< 9kg to 6kg will receive 2 mg BID for 7 days and 1mg BID thereafter;<6kg to 5kg will receive 1mg BID for 7 days and 0.5mg BID thereafter;<5kg to 4kg will receive 0.6mg twice daily for 7 days and 0.3mg BID thereafter;PK cohort neonates ≥ 2.6kg will receive 0.1mg BID. Dose will be adjusted as determined by PK measurements (ie, to 0.2mg BID, 0.1mg daily or dose will stay the same).For the post PK cohort Neonates ˂4kg to 2.6kg, if confirmed by PK sub analysis,subjects will receive 0.2mg BID for 7 days and 0.1mg BID thereafter. Receives: Drug: Apixaban; Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Composite of Major and Clinically Relevant Non-Major (CRNM) Bleeding
Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite.
Measured: From first dose (Day 1) up to 114 days
Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE) and VTE-Related Mortality
Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method.
Measured: From first dose (Day 1) up to 114 days
Secondary outcomes (10)
Percentage of Participants Who Died
Death due to any cause was assessed. 95% CI was calculated using the Agresti-Coull method.
Measured: From first dose (Day 1) up to 114 days
Percentage of Participants With Venous Thromboembolism (VTE)-Related Mortality
Participants were assessed for death due to Venous Thromboembolism (VTE).
Measured: From first dose (Day 1) up to 114 days
Number of Participants With Index Venous Thromboembolism (VTE) Status
Index VTE status was defined as the last image obtained during the Main treatment phase for each participant's comparison to baseline imaging. Index VTE status was classified as Recurrence-contiguous; Recurrence-new; Unchanged; Regression; Resolution; Indeterminate/Nondiagnostic. Participants could have multiple concomitant index events. Regression was defined as (ie, unequivocal decrease [>50%] of the total volume/mass of the thrombus compared to the index event)
Measured: From first dose (Day 1) up to 91 days
Percentage of Participants With Stroke
Participants were assessed for incidence of stroke.
Measured: From first dose (Day 1) up to 114 days
Percentage of Participants With Symptomatic and Asymptomatic Recurrent Venous Thromboembolism (VTE)
Recurrent VTE, defined as either contiguous progression or non-contiguous new thrombus and including, but not limited to deep vein thrombosis (DVT), pulmonary embolism (PE) and paradoxical embolism. 95% CI was from the Agresti-Coull method.
Measured: From first dose (Day 1) up to 114 days
Number of Participants With New Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE)
Participants were assessed for incidence of Symptomatic or Asymptomatic Deep Vein Thrombosis (DVT) and New Symptomatic or Asymptomatic Pulmonary Embolism (PE).
Measured: From first dose (Day 1) up to 114 days
Percentage of Participants With Other Symptomatic and Asymptomatic Venous Thromboembolism (VTE)
Other VTE included events such as cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, catheter-related VTE, and splanchnic thrombosis. If VTE event type was blank, it was included in the Other VTE. 95% CI was from the Agresti-Coull method.
Measured: From first dose (Day 1) up to 114 days
Number of Participants With Clinically Relevant Non-Major (CRNM) Bleeding, Major Bleeding and Minor Bleeding
Bleeding definitions are based on the Perinatal and Paediatric Haemostasis Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH) criteria. Major bleeding includes: (i) fatal bleeding; (ii) clinically overt bleeding with a decrease in Hgb of at least 20 g/L (2 g/dL) in 24 hours; (iii) retroperitoneal, pulmonary, intracranial, or central nervous system bleeding; and (iv) bleeding requiring surgical intervention in an operating suite (including interventional radiology). Clinically relevant non-major bleeding includes: (i) overt bleeding requiring a blood product not attributable to the participant's underlying condition; and (ii) bleeding requiring medical or surgical intervention to restore hemostasis, other than in an operating suite. Minor bleeding was defined as any overt or macroscopic evidence of bleeding that does not fulfill the above criteria for either major bleeding or clinically relevant, non-major bleeding.
Measured: From first dose (Day 1) up to 114 days
Blood Concentration of Apixaban (ng/mL)
Blood samples were collected to assess the apixaban concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 1.0 ng/mL for plasma samples, and 0.5 ng/mL for dried blood samples.
Measured: 3 hour (H), 12 H, 24 H at Day 3; pre and post dose at Day 14 and Day 42
Concentration of Plasma Anti-Factor Xa (ng/mL)
Blood samples were collected to assess the Anti-Factor Xa concentration at specified timepoints. Day 1 PK concentrations were only collected for participants in the Birth to ≤27 days arm. The lower limit of quantification (LLOQ) is 35.0 ng/mL.
Measured: Pre and post dose at Day 14 and Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2015 (estimated)
- Study start22 Nov 2015
- Primary completion30 Apr 2024
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 229 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02464969
- Sponsor's protocol ID
- B0661037
- Other IDs
- 2014-002606-20, CV185-325, 2014
- Status last verified
- Oct 2024
- First submitted
- 26 May 2015
- Last updated
- 29 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Brandao LR, Driscoll J, Newburger JW, Holzhauer S, Ahuja S, Rubio AE, Gaitonde P, Robertson A, Polinsky M, Revkin JH, Masiukiewicz U, O'Brien SH, Mitchell LG; Pediatric Apixaban VTE Study Investigators. Apixaban for the treatment of venous thromboembolic events in paediatric patients: an open-label, multicentre, randomised, controlled descriptive trial. Lancet Haematol. 2026 Jul;13(7):e471-e483. doi: 10.1016/S2352-3026(26)00107-9.
PubMed 42392108