Venous ThromboembolismPhase 3NCT01895777
Open Label Study Comparing Efficacy and Safety of Dabigatran Etexilate to Standard of Care in Paediatric Patients With Venous Thromboembolism (VTE)
A Phase 3 study testing dabigatran etexilate in people with Venous Thromboembolism, run by Boehringer Ingelheim at 65 sites in 26 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- dabigatran etexilate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 267 participants
- Where
- 65 sitesin 26 countries
- Study dates
- 25 Sep 2013to 14 Nov 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
65 sites in 26 countries.
65 sites in 26 countries
United States9 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Virginia Health System
Charlottesville, Virginia, 22908
Blank Children's Hospital
Des Moines, Iowa, 50309
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Miami
Miami, Florida, 33136
University of California Davis
Sacramento, California, 95817
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
St. Joseph's Children's Hospital
Tampa, Florida, 33607
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Russia7 sites
Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
Kazan', 420138
Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo
Kemerovo, 650002
Izmilovskaya Child City ClinHosp,Haematological Dept, Moscow
Moscow, 105077
Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol
Moscow, 125373
St.Petersburg State Pediatric Univ.Ministry of Healthcare RF
Saint Petersburg, 194100
Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery
Tyument, 625023
Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg
Yekaterinburg, 620134
Turkey (Türkiye)7 sites
Cukurova Universitesi Tip Fakultesi Cocuk Sagligi
Adana, 1330
Hacettepe Universitesi Tip Fakultesi
Ankara, 06100
Akdeniz Universitesi Tip Fakultesi
Antalya, 7058
Istanbul Universitesi Cerrahpasa Tip Fakultesi
Istanbul, 34098
Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH
Istanbul, 34303
Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali
Izmir, 35040
Necmettin Erbakan Universitesi Meram Tip Fakultesi
Konya, 42080
Czechia6 sites
University Hospital Brno
Brno, 61300
General Univ.hosp Hradec Kralove
Hradec Králové, 500 05
University Hospital Olomouc
Olomouc, 77900
University Hospital Ostrava
Ostrava, 70852
University Hospital Plzen, Plzen-Lochotin
Plzen-Lochotin, 304 60
University Hospital Motol
Prague, 15006
Brazil4 sites
HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
Campinas, 13059-740
Faculdade de Ciencias Medicas da UNICAMP
Campinas, 13083-970
PenSI - Pesquisa e Ensino em Saude Infantil
São Paulo, 01227-200
Instituto de Crianca / Hospital das Clínicas-FMUSP
São Paulo, 05403-000
Belgium3 sites
Brussels - UNIV Saint-Luc
Brussels, 1200
UNIV UZ Gent
Ghent, 9000
UZ Leuven
Leuven, 3000
Canada3 sites
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Austria2 sites
Medical University of Innsbruck
Innsbruck, 6020
AKH - Medical University of Vienna
Vienna, 1090
Germany2 sites
Universitätsklinikum Essen AöR
Essen, 45147
Universitätsklinikum Münster
Münster, 48149
Italy2 sites
Università degli Studi "La Sapienza"
Roma, 00161
Ospedale Infantile Regina Margherita
Torino, 10126
Mexico2 sites
Instituto Nacional de Pediatría
México D.F, 04530
Hospital Universitario Dr Jose Eleuterio Gonzalez
Nuevo León, 64460
Norway2 sites
Haukeland Universitetssykehus
Bergen, N-5021
Oslo Universitetssykehus HF, Rikshospitalet
Oslo, N-0372
Sweden2 sites
Sahlgrenska US, Göteborg
Gothenburg, 41345
Karolinska Univ. sjukhuset
Solna, 171 65
Ukraine2 sites
Reg.Children Hosp.Dnipropetrovsk
Dnipropetrovsk, 49100
Reg.Children Hosp,Vinnytsia
Vinnytsia, 21029
Denmark1 site
Rigshospitalet, København, Børneonkologisk Afsnit 5002
Copenhagen, 2100
Lithuania1 site
Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius
Vilnius, 08406
About this study
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
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
- Being tested
- dabigatran etexilate, standard of care
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dabigatran etexilateDrug
Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation
standard of careDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| dabigatran etexilate | Experimental | Dabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months Receives: Drug: dabigatran etexilate |
| standard of care | Active comparator | 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) Receives: Drug: standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Primary Endpoint
The primary endpoint was the combined endpoint of the proportions of patients with:
- Complete thrombus resolution
- Freedom from recurrent VTE
- Freedom from mortality related to VTE. The events outlined in the above combined primary endpoint were assessed by radiologists or other such qualified clinicians using an appropriate method such as ultrasound, echocardiography, venography, or CT scan, based on the location of the thrombus and the test used to perform the baseline assessment.
The primary efficacy endpoint contained 3 components. Each component was evaluated separately, and only if the criteria for all 3 components were satisfied, the primary endpoint was considered achieved.
Measured: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Secondary outcomes (12)
Freedom From Major Bleeding Events (MBEs)
Freedom from major bleeding events (MBEs), defined as either fatal bleeding, clinically overt bleeding associated with a decrease in haemoglobin of at least 20 g/L in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial or otherwise involves the central nervous system, or bleeding that requires intervention in an operating suite.
Measured: From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.
Steady State Plasma Concentrations of Total Dabigatran at Visit 3
Descriptive statistics for steady state plasma concentrations of total dabigatran etexilate at visit 3
Measured: From the time of randomisation until visit 3
Steady State Plasma Concentrations After at Least 3 Days Following Any Dabigatran Etexilate Dose Adjustment
Descriptive statistics for steady state plasma concentrations of total dabigatran etexilate after at least 3 days following any dabigatran etexilate dose adjustment
Measured: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Frequency of Dose Adjustment During the Treatment Phase
Frequency of dose adjustments (i.e. number of patients with dose adjustment), temporary and permanent discontinuation from therapy, and number of patients with laboratory monitoring requirements for dose
Measured: From first administration of trial medication until last administration of trial medication +6 days (residual effect period).
Frequency of Patients Switching the Type of Anti-coagulation Therapy Including Dabigatran Etexilate to Standard of Care Treatment and Switching From One Standard of Care Treatment to Another
Frequency of patients switching the type of anti-coagulation therapy including Dabigatran etexilate (DE) to standard of care (SoC) treatment and switching from one standard of care treatment to another.
For DE arm, only the switch from DE to SoC was counted, while for the SoC arm, all switches among SoC treatments were counted.
Measured: From first administration of trial medication until last administration of trial medication +6 days (residual effect period).
Freedom From Thrombus Progression at End of Therapy Compared With Baseline
Freedom from thrombus progression at end of therapy compared with baseline, based on adjudication-confirmed data.
Measured: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
All Bleeding Events
The number of participants with bleeding events includes major bleeding events (MBEs), clinically relevant non-major (CRNM) bleeding, minor bleeding events, any bleeding events, and the numbers of the combined endpoint of major and CRNM bleeding events was presented, based on adjudication-confirmed data.
Measured: From first administration of trial medication until last adminstration of trial medication +6 days (residual effect period). Up to 97 days.
All-cause Mortality
Patients being alive at the end of observational period will be censored for all-cause mortality at the date of patients' last date known to be alive, or the date of data cut-off whichever comes first.
Measured: From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.
All Components of the Primary Efficacy Endpoint
Patients with VTE-related death occurring between randomisation to Day 84 + 7 days were considered as not meeting the endpoint. The presence of recurrent VTE(s) was examined throughout the trial, and only the date of first occurrence was used for analysis. Assessment of index VTE status (best overall response) was scheduled on Day 84 ± 7 days (Visit 8) for patients who were alive without an early consent withdraw. In the case a Patient discontinued trial medication prematurely due to any reason the index VTE assessment took place at the early end of treatment visit.
Measured: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules)
Acceptability was defined as the overall ability and willingness of the patient to use the medicinal product. Questions regarding acceptability were to be answered by the patient and/or parent/caregiver (as applicable) and by the investigator/site staff.
Investigator questionnaire capsules: What is your impression about the patient's acceptability of DE intake? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).
Parents questionnaire capsules: How acceptable was the DE treatment for the child? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).
Patients questionnaire capsules: Was taking the study capsules easy or difficult? The score is 1 (Very easy), 2 (easy), 3 (neither easy nor difficult), 4 (difficult) and 5 (very difficult).
Scores refers to the end of treatment.
Measured: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets)
Acceptability was defined as the overall ability and willingness of the patient to use the medicinal product. Questions regarding acceptability were to be answered by the patient and/or parent/caregiver (as applicable) and by the investigator/site staff.
Investigator questionnaire pellets: What is your impression about the patient's acceptability of DE intake? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).
Parents questionnaire pellets: Do you think that spitting occurs? The score is 1 (Never), 2 (sometimes) and 3 (often).
Scores refers to the end of treatment.
Measured: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF)
Acceptability was defined as the overall ability and willingness of the patient to use the medicinal product. Questions regarding acceptability were to be answered by the patient and/or parent/caregiver (as applicable) and by the investigator/site staff.
Investigator questionnaire flavoured OLF: What is your impression about the patient's acceptability of DE intake? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).
Investigator questionnaire unflavoured OLF: What is your impression about the patient's acceptability of DE intake? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).
Parents questionnaire flavoured OLF.: Do you think spitting occurs? The score ranges form 1 (never), 2 ( sometimes) to 3 (often).
Parents questionnaire unflavoured OLF:Do you think spitting occurs? The score ranges form 1 (never), 2 ( sometimes) to 3 (often).
Scores refers to the end of treatment.
Measured: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2013 (estimated)
- Study start25 Sep 2013
- Primary completion16 Oct 2019
- Study completion14 Nov 2019
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 (4)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 Boehringer IngelheimThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 267 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01895777
- Sponsor's protocol ID
- 1160.106
- Other IDs
- 2013-002114-12
- Status last verified
- Jun 2020
- First submitted
- 4 Jul 2013
- Last updated
- 7 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 38348778Brandao 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.
PubMed 36150047Halton 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.
PubMed 33290737Albisetti 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.
PubMed 30046738
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01895777
- Acronym / sponsor ID
- 1160.106
- Conditions
- Venous Thromboembolism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 267 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2013 (actual)
- Primary completion
- 16 Oct 2019 (actual)
- Study completion
- 14 Nov 2019 (actual)
- First posted
- 11 Jul 2013 (estimated)
- Results
- Posted 7 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dabigatran etexilate | Experimental | Drug: dabigatran etexilateDabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months |
| standard of care | Active comparator | Drug: standard of careLow 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) |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dabigatran etexilateAge and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation | Drug | dabigatran etexilate |
| standard of careLow 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 |
Primary outcome
Composite Primary Endpoint
Time frame: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
The primary endpoint was the combined endpoint of the proportions of patients with: * Complete thrombus resolution * Freedom from recurrent VTE * Freedom from mortality related to VTE. The events outlined in the above combined primary endpoint were assessed by radiologists or other such qualified clinicians using an appropriate method such as ultrasound, echocardiography, venography, or CT scan, based on the location of the thrombus and the test used to perform the baseline assessment. The primary efficacy endpoint contained 3 components. Each component was evaluated separately, and only if the criteria for all 3 components were satisfied, the primary endpoint was considered achieved.
12 secondary outcomes
Freedom From Major Bleeding Events (MBEs)
Time frame: From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.
Steady State Plasma Concentrations of Total Dabigatran at Visit 3
Time frame: From the time of randomisation until visit 3
Steady State Plasma Concentrations After at Least 3 Days Following Any Dabigatran Etexilate Dose Adjustment
Time frame: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Frequency of Dose Adjustment During the Treatment Phase
Time frame: From first administration of trial medication until last administration of trial medication +6 days (residual effect period).
Frequency of Patients Switching the Type of Anti-coagulation Therapy Including Dabigatran Etexilate to Standard of Care Treatment and Switching From One Standard of Care Treatment to Another
Time frame: From first administration of trial medication until last administration of trial medication +6 days (residual effect period).
Freedom From Thrombus Progression at End of Therapy Compared With Baseline
Time frame: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
All Bleeding Events
Time frame: From first administration of trial medication until last adminstration of trial medication +6 days (residual effect period). Up to 97 days.
All-cause Mortality
Time frame: From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.
All Components of the Primary Efficacy Endpoint
Time frame: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules)
Time frame: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets)
Time frame: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF)
Time frame: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38348778Albisetti 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.
- Derived from this study: PubMed 36150047Brandao 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.
- Derived from this study: PubMed 33290737Halton 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.
- Derived from this study: PubMed 30046738Albisetti 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
65 sites in 26 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing dabigatran etexilate in people with Venous Thromboembolism, run by Boehringer Ingelheim at 65 sites in 26 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, Russia, Turkey (Türkiye), Czechia, Brazil and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Primary Endpoint (time frame: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01895777, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020.