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Open Label Study Comparing Efficacy and Safety of Dabigatran Etexilate to Standard of Care in Paediatric Patients With Venous Thromboembolism (VTE)

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ClinicalTrials.gov Identifier: NCT01895777
Recruitment Status : Active, not recruiting
First Posted : July 11, 2013
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
The main objectives of this large phase IIb/III paediatric study are to assess the efficacy and safety of dabigatran etexilate relative to standard of care and to document the appropriateness of the proposed dabigatran etexilate dosing algorithm for use in patients from birth to less than 18 years of age.

Condition or disease Intervention/treatment Phase
Venous Thromboembolism Drug: dabigatran etexilate Drug: standard of care Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Randomized, Parallel-group, Active-controlled, Multi-centre Non-inferiority Study of Dabigatran Etexilate Versus Standard of Care for Venous Thromboembolism Treatment in Children From Birth to Less Than 18 Years of Age
Actual Study Start Date : September 25, 2013
Estimated Primary Completion Date : October 16, 2019
Estimated Study Completion Date : November 20, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: dabigatran etexilate
Dabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months
Drug: dabigatran etexilate
Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation

Active Comparator: standard of care
Low molecular weight heparin, vitamin K antagonist or fondaparinux prescribed in an open label fashion for 3 months (these medications will not supplied in this study as IMP)
Drug: standard of care
Low molecular weight heparin, vitamin K antagonist or fondaparinux prescribed in an open label fashion for 3 months (these medications will not supplied in this study as IMP)




Primary Outcome Measures :
  1. A combined efficacy endpoint of complete thrombus resolution plus freedom from recurrent VTE plus freedom from mortality related to VTE [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Cpre,ss (pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose) taken at 10 to 16 hours after the last dose (trough) [ Time Frame: 3, 7, 21, 42, 63 and 84 days ]
  2. Frequency of dose adjustments [ Time Frame: 12 weeks ]
  3. Frequency of switch of type of anti-coagulation therapy (including dabigatran to SOC) and a switch from an intended standard of care treatment to another [ Time Frame: 12 weeks ]
  4. Assessment of the acceptability of an age-appropriate formulation at end of therapy [ Time Frame: 3 weeks and 12 weeks ]
  5. All bleeding events [ Time Frame: 12 weeks ]
  6. All-cause mortality [ Time Frame: 12 weeks ]
  7. All components of the primary efficacy endpoints [ Time Frame: 12 weeks ]
  8. Pharmacodynamic assessments (aPTT, ecarin clotting time (ECT) and diluted thrombin time (dTT)(Anti-Factor IIa activity)) at visit 3 (after at least six consecutive dabigatran doses) and after 3 days following any dabigatran dose adjustment [ Time Frame: 3, 7, 21, 42, 63 and 84 days ]
  9. Frequency of temporary discontinuation from therapy [ Time Frame: 12 weeks ]
  10. Frequency of permanent discontinuation from therapy [ Time Frame: 12 weeks ]
  11. Number of subjects with laboratory monitoring requirements for dose adjustment during the treatment phase [ Time Frame: 12 weeks ]
  12. Freedom from thrombus progression at end of therapy (day 84 after randomisation or eEOT, whichever comes first) [ Time Frame: 12 weeks ]
  13. Freedom from major bleeding events (a safety endpoint) [ Time Frame: 12 weeks ]
  14. C2,ss (concentration of the analyte in plasma at steady state at 2 hours after administration of the last dose) taken at 1 to 3 hours after the last dose (peak) [ Time Frame: 3, 7, 21, 42, 63 and 84 days ]


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

Inclusion criteria:

  • Male or female subjects 0 to less than 18 years of age at the time of informed consent / assent
  • Documented diagnosis of clinically stable VTE (e.g. DVT, PE, central line thrombosis, sinus vein thrombosis) per investigator judgment, initially treated (minimum of 5 to 7 days, but not longer than 21 days) with parenteral anticoagulation therapy, such as unfractionated heparin (UFH) or a low molecular weight heparin (LMWH).
  • Clinical indication for at least 3 month of treatment with anticoagulants for the VTE episode defined under the above inclusion criterion.
  • Written informed consent provided by the patient's parent or legal guardian and assent provided by the patient (if applicable) at the time of informed consent form (ICF) signature according to local regulations.

Exclusion criteria:

  • Conditions associated with an increased risk of bleeding
  • Renal dysfunction (eGFR < 50 mL/min/1.73m^2 using the Schwartz formula) or requirement for dialysis. eGFR retesting during the screening period is allowed (once).
  • Active infective endocarditis
  • Subjects with a heart valve prosthesis requiring anticoagulation.
  • Hepatic disease:

Active liver disease, including known active hepatitis A, B or C or, Persistent alanine aminotransferase (ALT) or aspartate transaminase (AST) or alkaline phosphatase (AP) > 3 × upper limit of normal (ULN) within 3 months of screening

  • Pregnant or breast feeding females. Females who have reached menarche and are not using a medically accepted contraceptive method per local guidelines. Acceptable methods of birth control must be used in a correct and consistent manner
  • Patients in stratum 3 (0 to < 2 years) with gestational age at birth < 37 weeks or with body weight lower than the 3rd percentile
  • Anemia (hemoglobin < 80g/L) or thrombocytopenia (platelet count < 80 x 109/L) at screening. Transfusions during the screening period are allowed, provided that a satisfactory hemoglobin or platelet level is attained prior to visit 2
  • Patients who have taken prohibited or restricted medication within one week of the first dose of study medication other than medication for prior VTE treatment and P-glycoprotein inhibitors..
  • Patients who have received an investigational drug in the past 30 days prior to screening
  • Patients who are allergic/sensitive to any component of the study medication including solvent
  • Patients or parents/legal guardians considered unreliable to participate in the trial per investigator judgment or any condition which would present a safety hazard to the patient based on investigator judgment
  • Patients or parents/legal guardians who are unwilling or unable to undergo or permit repeat of the baseline imaging tests required to confirm thrombus resolution at study day 84 (or eEOT, whichever comes first) or in whom repeating such imaging tests at these pre-specified time points may not be medically in the patient's best interest. Examples may include unwarranted radiation exposure as a result of a repeat CT scan at day 84 for a patient with an isolated case of pulmonary embolism evaluated at baseline solely by a CT scan. In such cases, the baseline radiological assessment (e.g. CT) may be supplemented with an acceptable non-radiological assessment at baseline (e.g. MRI) which could then be repeated at day 84 hence alleviating any potential unwarranted radiation exposure.
  • Further exclusion criteria apply

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): NCT01895777


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Locations
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United States, California
University of California Davis
Sacramento, California, United States, 95817
United States, Florida
University of Miami
Miami, Florida, United States, 33136
St. Joseph's Children's Hospital
Tampa, Florida, United States, 33607
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
University Of Minnesota, Masonic Children's Hospital
Minneapolis, Minnesota, United States, 55454
United States, Missouri
Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, United States, 63104
United States, Nevada
Alliance for Childhood Diseases
Las Vegas, Nevada, United States, 89135
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15224
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
Argentina
Hospital General de Niños Pedro de Elizalde
Caba, Argentina, C1270AAN
Austria
Medical University of Innsbruck
Innsbruck, Austria, 6020
AKH - Medical University of Vienna
Wien, Austria, 1090
Belgium
Brussels - UNIV UZ Brussel
Brussel, Belgium, 1090
Brussels - UNIV Saint-Luc
Bruxelles, Belgium, 1200
UNIV UZ Gent
Gent, Belgium, 9000
UZ Leuven
Leuven, Belgium, 3000
Brazil
HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
Campinas, Brazil, 13059-740
Faculdade de Ciencias Medicas da UNICAMP
Campinas, Brazil, 13083-970
PenSI - Pesquisa e Ensino em Saude Infantil
Sao Paulo, Brazil, 01227-200
Instituto de Oncologia Pediatrica - IOP / GRAAC - UNIFESP
Sao Paulo, Brazil, 04039-001
Instituto de Crianca / Hospital das Clínicas-FMUSP
Sao Paulo, Brazil, 05403-000
Canada, Ontario
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
CHU Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Czechia
University Hospital Brno
Brno, Czechia, 61300
General Univ.hosp Hradec Kralove
Hradec Kralove, Czechia, 500 05
University Hospital Olomouc
Olomouc, Czechia, 77900
University Hospital Ostrava
Ostrava, Czechia, 70852
University Hospital Plzen, Plzen-Lochotin
Plzen-Lochotin, Czechia, 304 60
University Hospital Motol
Prague, Czechia, 15006
Denmark
Rigshospitalet, København, Børneonkologisk Afsnit 5002
Copenhagen, Denmark, 2100
Finland
HUS, Uusi lastensairaala
Helsinki, Finland, 00280
TaUH, Pediatric Early Phase Trial Unit
Tampere, Finland, 33520
France
HOP de la Cavale Blanche
Brest cedex, France, 29609
HOP Timone
Marseille, France, 13005
Germany
Universitätsklinikum Essen AöR
Essen, Germany, 45147
Universitätsmedizin Göttingen, Georg-August-Universität
Göttingen, Germany, 37075
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany, 55131
Universitätsklinikum Münster
Münster, Germany, 48149
Greece
"Aghia Sophia" Children's Hospital
Athens, Greece, 11527
Hungary
University Debrecen Hospital
Debrecen, Hungary, 4032
Israel
Shaare Zedek Medical Center, Jerusalem 91031
Jerusalem, Israel, 9103102
Italy
Università degli Studi "La Sapienza"
Roma, Italy, 00161
Osp. Pediatrico Bambin Gesù
Roma, Italy, 00165
Ospedale Infantile Regina Margherita
Torino, Italy, 10126
Lithuania
Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius
Vilnius, Lithuania, 08406
Mexico
Instituto Nacional de Pediatría
México D.F, Mexico, 04530
Hospital Universitario Dr Jose Eleuterio Gonzalez
Nuevo León, Mexico, 64460
Norway
Haukeland Universitetssykehus
Bergen, Norway, N-5021
Oslo Universitetssykehus HF, Rikshospitalet
Oslo, Norway, N-0372
Russian Federation
Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
Kazan, Russian Federation, 420138
Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo
Kemerovo, Russian Federation, 650002
Izmilovskaya Child City ClinHosp,Haematological Dept, Moscow
Moscow, Russian Federation, 105077
Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol
Moscow, Russian Federation, 125373
St.Petersburg State Pediatric Univ.Ministry of Healthcare RF
St. Petersburg, Russian Federation, 194100
Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery
Tyument, Russian Federation, 625023
State Budget Healthcare Institution "Republican children's clinical hospital"
Ufa, Russian Federation, 450106
Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg
Yekaterinburg, Russian Federation, 620134
Spain
Hospital General Universitario Gregorio Marañón
Madrid, Spain, 28007
Hospital Infantil Universitario Niño Jesus
Madrid, Spain, 28009
Sweden
Sahlgrenska US, Göteborg
Göteborg, Sweden, 41345
Karolinska Univ. sjukhuset
Solna, Sweden, 171 65
Switzerland
University Hospital of Lausanne
Lausanne, Switzerland, 1011
Universitäts-Kinderspital
Zürich, Switzerland, 8032
Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan, 407
Thailand
King Chulalongkorn Memorial Hospital
Bangkok, Thailand, 10330
Siriraj Hospital
Bangkok, Thailand, 10700
Turkey
Cukurova Universitesi Tip Fakultesi Cocuk Sagligi
Adana, Turkey, 1330
Hacettepe Universitesi Tip Fakultesi
Ankara, Turkey, 06100
Akdeniz Universitesi Tip Fakultesi
Antalya, Turkey, 7058
Istanbul Universitesi Cerrahpasa Tip Fakultesi
Istanbul, Turkey, 34098
Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH
Istanbul, Turkey, 34303
Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali
Izmir, Turkey, 35040
Necmettin Erbakan Universitesi Meram Tip Fakultesi
Konya, Turkey, 42080
Ukraine
Reg.Children Hosp.Dnipropetrovsk
Dnipropetrovsk, Ukraine, 49100
Western Ukrainian Spec.Children Med.Center,Lviv
Lviv, Ukraine, 79035
Reg.Children Hosp,Vinnytsia
Vinnytsya, Ukraine, 21029
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01895777     History of Changes
Other Study ID Numbers: 1160.106
2013-002114-12 ( EudraCT Number )
First Posted: July 11, 2013    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
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Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants