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

NCT ID: NCT01895777

Last Updated: 2020-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-25
• Study Completion Date: 2019-11-14

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.

Conditions

Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dabigatran etexilate

Dabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months

Group Type: EXPERIMENTAL

dabigatran etexilate

Intervention Type: DRUG

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

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)

Group Type: ACTIVE_COMPARATOR

standard of care

Intervention Type: DRUG

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)

Interventions

dabigatran etexilate

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

Intervention Type: 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)

Intervention Type: DRUG

Eligibility 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.

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

University of California Davis

Sacramento, California, United States

University of Miami

Miami, Florida, United States

St. Joseph's Children's Hospital

Tampa, Florida, United States

Blank Children's Hospital

Des Moines, Iowa, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Hospital General de Niños Pedro de Elizalde

CABA, , Argentina

Medical University of Innsbruck

Innsbruck, , Austria

AKH - Medical University of Vienna

Vienna, , Austria

Brussels - UNIV Saint-Luc

Brussels, , Belgium

UNIV UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas

Campinas, , Brazil

Faculdade de Ciencias Medicas da UNICAMP

Campinas, , Brazil

PenSI - Pesquisa e Ensino em Saude Infantil

São Paulo, , Brazil

Instituto de Crianca / Hospital das Clínicas-FMUSP

São Paulo, , Brazil

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

University Hospital Brno

Brno, , Czechia

General Univ.hosp Hradec Kralove

Hradec Králové, , Czechia

University Hospital Olomouc

Olomouc, , Czechia

University Hospital Ostrava

Ostrava, , Czechia

University Hospital Plzen, Plzen-Lochotin

Plzen-Lochotin, , Czechia

University Hospital Motol

Prague, , Czechia

Rigshospitalet, København, Børneonkologisk Afsnit 5002

Copenhagen, , Denmark

TaUH, Pediatric Early Phase Trial Unit

Tampere, , Finland

HOP de la Cavale Blanche

Brest, , France

Universitätsklinikum Essen AöR

Essen, , Germany

Universitätsklinikum Münster

Münster, , Germany

"Aghia Sophia" Children's Hospital

Athens, , Greece

University Debrecen Hospital

Debrecen, , Hungary

Shaare Zedek Medical Center, Jerusalem 91031

Jerusalem, , Israel

Università degli Studi "La Sapienza"

Roma, , Italy

Ospedale Infantile Regina Margherita

Torino, , Italy

Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius

Vilnius, , Lithuania

Instituto Nacional de Pediatría

México D.F, , Mexico

Hospital Universitario Dr Jose Eleuterio Gonzalez

Nuevo León, , Mexico

Haukeland Universitetssykehus

Bergen, , Norway

Oslo Universitetssykehus HF, Rikshospitalet

Oslo, , Norway

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

Kazan', , Russia

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

Kemerovo, , Russia

Izmilovskaya Child City ClinHosp,Haematological Dept, Moscow

Moscow, , Russia

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

Moscow, , Russia

St.Petersburg State Pediatric Univ.Ministry of Healthcare RF

Saint Petersburg, , Russia

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

Tyument, , Russia

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

Yekaterinburg, , Russia

Hospital Infantil Universitario Niño Jesus

Madrid, , Spain

Sahlgrenska US, Göteborg

Gothenburg, , Sweden

Karolinska Univ. sjukhuset

Solna, , Sweden

Universitäts-Kinderspital

Zurich, , Switzerland

Taichung Veterans General Hospital

Taichung, , Taiwan

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Cukurova Universitesi Tip Fakultesi Cocuk Sagligi

Adana, , Turkey (Türkiye)

Hacettepe Universitesi Tip Fakultesi

Ankara, , Turkey (Türkiye)

Akdeniz Universitesi Tip Fakultesi

Antalya, , Turkey (Türkiye)

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali

Izmir, , Turkey (Türkiye)

Necmettin Erbakan Universitesi Meram Tip Fakultesi

Konya, , Turkey (Türkiye)

Reg.Children Hosp.Dnipropetrovsk

Dnipropetrovsk, , Ukraine

Reg.Children Hosp,Vinnytsia

Vinnytsia, , Ukraine

Countries

United States; Argentina; Austria; Belgium; Brazil; Canada; Czechia; Denmark; Finland; France; Germany; Greece; Hungary; Israel; Italy; Lithuania; Mexico; Norway; Russia; Spain; Sweden; Switzerland; Taiwan; Thailand; Turkey (Türkiye); Ukraine

References

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.

Reference Type: DERIVED

PMID: 38348778 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36150047 (View on PubMed)

Halton J, Brandao LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Sharathkumar A, Svirin P, Gorbatikov K, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Reilly P, Brueckmann M, Albisetti M; DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021 Jan;8(1):e22-e33. doi: 10.1016/S2352-3026(20)30368-9. Epub 2020 Dec 5.

Reference Type: DERIVED

PMID: 33290737 (View on PubMed)

Albisetti M, Biss B, Bomgaars L, Brandao LR, Brueckmann M, Chalmers E, Gropper S, Harper R, Huang F, Luciani M, Manastirski I, Mitchell LG, Tartakovsky I, Wang B, Halton JML. Design and rationale for the DIVERSITY study: An open-label, randomized study of dabigatran etexilate for pediatric venous thromboembolism. Res Pract Thromb Haemost. 2018 Mar 25;2(2):347-356. doi: 10.1002/rth2.12086. eCollection 2018 Apr.

Reference Type: DERIVED

PMID: 30046738 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-002114-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1160.106

Identifier Type: -

Identifier Source: org_study_id