Clinical trial NCT02197416: Safety of Dabigatran Etexilate in Blood Clot Prevention in Children
Official title: Open Label, Single Arm Safety Prospective Cohort Study of Dabigatran Etexilate for Secondary Prevention of Venous Thromboembolism in Children From 0 to Less Than 18 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Secondary Prevention
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-22
Enrollment: 214
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This open-label, single arm prospective cohort study will assess the safety of dabigatran etexilate in secondary prevention of venous thromboembolism in paediatric patients. Children from 0 to less than 18 years of age will be eligible to participate.


Eligibility criteria: Inclusion criteria:

* Male or female subjects 0 to less than 18 years of age at the time of informed consent / assent
* Previously documented objective diagnosis of VTE, followed by completed course of initial VTE treatment for at least 3 months (in case of VKA - intended INR between 2 and 3) or completed study treatment (i.e. reached Visit 8) in the 1160.106 trial. Patients, who during the treatment phase of 1160.106 trial were switched from dabigatran etexilate to SOC arm for any reason, are not eligible for this study.
* Presence of an unresolved clinical risk factor requiring further anticoagulation for secondary VTE prevention (e.g. central venous line, underlying disease, thrombophilia, etc.)
* Written informed consent form (ICF) provided by the patient's parent or legal guardian and assent provided by the patient (if applicable) at the time of ICF signature according to local regulations.
* Further inclusion criteria apply

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 an acceptable method of birth control, or do not plan to continue using this method throughout the study and / or do not agree to adhere to pregnancy testing required by this protocol
* Patients in age group 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 restricted medication prior to first dose of study medication
* Patients who have received an investigational drug in the past 30 days prior to screening, except patients who have completed the treatment period (up to Visit 8) in 1160.106 trial
* 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
* Further exclusion criteria apply

Primary outcomes:
measure: Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months
timeFrame: At month 6 (Week 26) and 12 (Week 52) of on treatment period
measure: Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months
timeFrame: At month 6 (Week 26) and month 12 (Week 52) of on treatment period
measure: Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months
timeFrame: At month 6 (Week 26) and 12 (Week 52) of on treatment period
Secondary outcomes:
measure: Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months
timeFrame: At month 6 (Week 26) and 12 (Week 52) of on treatment period
measure: Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period
timeFrame: From first DE administration to 3 days of residual effect period after last DE administration, up to 52 weeks+ 3 days
measure: Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)
timeFrame: At Visit 3 (day 4 after first dose of trial medication)
measure: Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)
timeFrame: Pharmacodynamics (PD) samples were collected from first dose of trial medication at day 1 and day 4, 22, 43, 85, 127, 183, 239 and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.
measure: Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)
timeFrame: At Visit 3 (day 4 after first dose of trial medication)
measure: Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)
timeFrame: Pharmacodynamics (PD) samples were collected from first dose of trial medication at day 1 and day 4, 22, 43, 85, 127, 183, 239 and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.
measure: Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)
timeFrame: At Visit 3 (day 4 after first dose of trial medication)
measure: Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)
timeFrame: dTT values were collected at day 4, 22, 43, 85, 127, 183, 239, and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Children's Hospital
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases
state: Nevada
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Wien
country: Austria
facility: AKH - Medical University of Vienna
city: Brussel
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Campinas
country: Brazil
facility: HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
city: Campinas
country: Brazil
facility: Faculdade de Ciencias Medicas da UNICAMP
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia Pediatrica - IOP / GRAAC - UNIFESP
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Brno
country: Czechia
facility: University Hospital Brno
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Plzen - Lochotin
country: Czechia
facility: University Hospital Plzen, Plzen-Lochotin
city: Prague
country: Czechia
facility: University Hospital Motol
city: Copenhagen
country: Denmark
facility: Rigshospitalet, København, Børneonkologisk Afsnit 5002
city: Marseille
country: France
facility: HOP Timone
city: Essen
country: Germany
facility: Universitätsklinikum Essen AöR
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Georg-August-Universität
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Debrecen
country: Hungary
facility: University Debrecen Hospital
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center, Jerusalem 91031
city: Palermo
country: Italy
facility: A.O. Univ. Policlinico "Paolo Giaccone"
city: Roma
country: Italy
facility: Università degli Studi "La Sapienza"
city: Roma
country: Italy
facility: Osp. Pediatrico Bambin Gesù
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita
city: Vilnius
country: Lithuania
facility: Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius
city: Mexico DF
country: Mexico
facility: Instituto Nacional de Pediatría
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Rikshospitalet
city: Kazan
country: Russian Federation
facility: Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
city: Kemerovo
country: Russian Federation
facility: Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo
city: Moscow
country: Russian Federation
facility: Morozovskaya Children Clin.Hosp.,Haematological Dept, Moscow
city: Moscow
country: Russian Federation
facility: Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol
city: St. Petersburg
country: Russian Federation
facility: St.Petersburg State Pediatric Univ.Ministry of Healthcare RF
city: Tyument
country: Russian Federation
facility: Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery
city: Ufa
country: Russian Federation
facility: State Budget Healthcare Institution "Republican children's clinical hospital"
city: Yekaterinburg
country: Russian Federation
facility: Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg
city: Solna
country: Sweden
facility: Karolinska Univ. sjukhuset
city: Zürich
country: Switzerland
facility: Universitäts-Kinderspital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Adana
country: Turkey
facility: Cukurova Universitesi Tip Fakultesi Cocuk Sagligi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali
city: Konya
country: Turkey
facility: Necmettin Erbakan Universitesi Meram Tip Fakultesi
city: Dnipropetrovsk
country: Ukraine
facility: Reg.Children Hosp.Dnipropetrovsk
city: Lviv
country: Ukraine
facility: Western Ukrainian Spec.Children Med.Center,Lviv
city: Vinnytsya
country: Ukraine
facility: Reg.Children Hosp,Vinnytsia
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Brandao LR, Tartakovsky I, Albisetti M, Halton J, Bomgaars L, Chalmers E, Luciani M, Saracco P, Felgenhauer J, Lvova O, Simetzberger M, Sun Z, Mitchell LG. Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia. Blood Adv. 2022 Nov 22;6(22):5908-5923. doi: 10.1182/bloodadvances.2021005681.
citation: Brandao LR, Albisetti M, Halton J, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Svirin P, Kuhn T, Zapletal O, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Brueckmann M, Luciani M; DIVERSITY Study Investigators. Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children. Blood. 2020 Feb 13;135(7):491-504. doi: 10.1182/blood.2019000998.