Safety of Dabigatran Etexilate in Blood Clot Prevention in Children

NCT02197416 | Completed Phase 3 Results

• 2 other identifiers: 1160.1082014-000583-18
• Study Type: interventional
• Target: 214
• Locations: 22 countries
• Sites: 62

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.

Conditions

Venous Thromboembolism; Secondary Prevention

Outcome Measures

Primary Outcomes (3)

• Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months

  The event-free probability of first recurrence of VTE were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience recurrent VTE at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-VTE related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

  At month 6 (Week 26) and 12 (Week 52) of on treatment period

• Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months

  The event-free probability of major or minor (including CRNM) bleeding event were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience major or minor (including CRNM) bleeding event at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-bleeding related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

  At month 6 (Week 26) and month 12 (Week 52) of on treatment period

• Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months

  The event-free probability of mortality overall and related to thrombotic or thromboembolic events were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience mortality overall and related to thrombotic or thromboembolic events at the time of analysis, dropped out from the trial early, were lost to follow-up, were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

  At month 6 (Week 26) and 12 (Week 52) of on treatment period

Secondary Outcomes (8)

• Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months

  At month 6 (Week 26) and 12 (Week 52) of on treatment period

• Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period

  From first DE administration to 3 days of residual effect period after last DE administration, up to 52 weeks+ 3 days

• Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)

  At Visit 3 (day 4 after first dose of trial medication)

• Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)

  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.

• Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)

  At Visit 3 (day 4 after first dose of trial medication)

Study Arms (1)

dabigatran etexilate

EXPERIMENTAL

Drug: dabigatran etexilate

Interventions

dabigatran etexilate DRUG

Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation

dabigatran etexilate

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (62)

University of California Davis

Sacramento, California, 95817, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

St. Joseph's Children's Hospital

Tampa, Florida, 33607, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242-1083, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Alliance for Childhood Diseases

Las Vegas, Nevada, 89135, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Brussels - UNIV UZ Brussel

Brussels, 1090, Belgium

Location

UNIV UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas

Campinas, 13059-740, Brazil

Location

Faculdade de Ciencias Medicas da UNICAMP

Campinas, 13083970, Brazil

Location

Instituto de Oncologia Pediatrica - IOP / GRAAC - UNIFESP

São Paulo, 04039-001, Brazil

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

CHU Sainte-Justine

Montreal, Ontario, H3T 1C5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

University Hospital Brno

Brno, 61300, Czechia

Location

University Hospital Olomouc

Olomouc, 77900, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

University Hospital Plzen, Plzen-Lochotin

Plzen - Lochotin, 304 60, Czechia

Location

University Hospital Motol

Prague, 15006, Czechia

Location

Rigshospitalet, København, Børneonkologisk Afsnit 5002

Copenhagen, 2100, Denmark

Location

HOP Timone

Marseille, 13005, France

Location

Universitätsklinikum Essen AöR

Essen, 45147, Germany

Location

Universitätsmedizin Göttingen, Georg-August-Universität

Göttingen, 37075, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

University Debrecen Hospital

Debrecen, 4032, Hungary

Location

Shaare Zedek Medical Center, Jerusalem 91031

Jerusalem, 9103102, Israel

Location

A.O. Univ. Policlinico "Paolo Giaccone"

Palermo, 90127, Italy

Location

Università degli Studi "La Sapienza"

Roma, 00161, Italy

Location

Osp. Pediatrico Bambin Gesù

Roma, 00165, Italy

Location

Ospedale Infantile Regina Margherita

Torino, 10126, Italy

Location

Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius

Vilnius, 08406, Lithuania

Location

Instituto Nacional de Pediatría

Mexico City, 04530, Mexico

Location

Haukeland Universitetssykehus

Bergen, N-5021, Norway

Location

Oslo Universitetssykehus HF, Rikshospitalet

Oslo, N-0372, Norway

Location

Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan

Kazan', 420138, Russia

Location

Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo

Kemerovo, 650002, Russia

Location

Morozovskaya Children Clin.Hosp.,Haematological Dept, Moscow

Moscow, 119049, Russia

Location

Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol

Moscow, 125373, Russia

Location

St.Petersburg State Pediatric Univ.Ministry of Healthcare RF

Saint Petersburg, 194100, Russia

Location

Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery

Tyument, 625023, Russia

Location

State Budget Healthcare Institution "Republican children's clinical hospital"

Ufa, 450106, Russia

Location

Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg

Yekaterinburg, 620134, Russia

Location

Karolinska Univ. sjukhuset

Solna, 171 65, Sweden

Location

Universitäts-Kinderspital

Zurich, 8032, Switzerland

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Cukurova Universitesi Tip Fakultesi Cocuk Sagligi

Adana, 1330, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz Universitesi Tip Fakultesi

Antalya, 7058, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH

Istanbul, 34303, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali

Izmir, 35040, Turkey (Türkiye)

Location

Necmettin Erbakan Universitesi Meram Tip Fakultesi

Konya, 42080, Turkey (Türkiye)

Location

Reg.Children Hosp.Dnipropetrovsk

Dnipropetrovsk, 49100, Ukraine

Location

Western Ukrainian Spec.Children Med.Center,Lviv

Lviv, 79035, Ukraine

Location

Reg.Children Hosp,Vinnytsia

Vinnytsia, 21029, Ukraine

Location

Related Publications (3)

• Albisetti M, Tartakovsky I, Halton J, Bomgaars L, Chalmers E, Mitchell LG, Luciani M, Nurmeev I, Gorbatikov K, Miede C, Brueckmann M, Brandao LR; Study Investigators. Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease. J Am Heart Assoc. 2024 Feb 20;13(4):e028957. doi: 10.1161/JAHA.122.028957. Epub 2024 Feb 13.

  PMID: 38348778 DERIVED

• 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.

  PMID: 36150047 DERIVED

• 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.

  PMID: 31805182 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 22, 2014
• Study Start: September 29, 2014
• Primary Completion: October 16, 2019
• Study Completion: November 19, 2019
• Last Updated: June 4, 2020
• Results First Posted: June 4, 2020

Record last verified: 2020-05

Locations

CA (4); CH (1); TU (7); DE (3); IL (1); FR (1); HU (1); TW (1); UA (3); IT (4); DK (1); LI (1); BE (3); RU (8); BR (3); CZ (5); AU (1); TH (1); NO (2); US (9); ME (1); SE (1)