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NCT02197416

Safety of Dabigatran Etexilate in Blood Clot Prevention in Children

Completed Phase 3 Results posted Last updated 4 June 2020
What this trial tests

Phase 3 trial testing dabigatran etexilate in Venous Thromboembolism in 214 participants. Completed in 19 November 2019.

Timeline
29 September 2014
Primary endpoint
16 October 2019
19 November 2019

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeprevention
Enrollment214
Start date29 September 2014
Primary completion16 October 2019
Estimated completion19 November 2019
Sites62 locations across Italy, Taiwan, Denmark, Russia, Belgium, Sweden, Mexico, Lithuania

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Under 18, any sex, with Venous Thromboembolism or Secondary Prevention. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months Primary · At month 6 (Week 26) and 12 (Week 52) of on treatment period

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.

6 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)1.0001.000 – 1.000
Dabigatran Etexilate (2 to <12 Years)1.0001.000 – 1.000
Dabigatran Etexilate (12 to <18 Years)0.9790.937 – 0.993
12 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)1.0001.000 – 1.000
Dabigatran Etexilate (2 to <12 Years)1.0001.000 – 1.000
Dabigatran Etexilate (12 to <18 Years)0.9790.937 – 0.993
Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months Primary · At month 6 (Week 26) and month 12 (Week 52) of on treatment period

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.

6 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)0.8890.433 – 0.984
Dabigatran Etexilate (2 to <12 Years)0.8940.706 – 0.965
Dabigatran Etexilate (12 to <18 Years)0.7530.675 – 0.815
12 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)0.8890.433 – 0.984
Dabigatran Etexilate (2 to <12 Years)0.8310.592 – 0.936
Dabigatran Etexilate (12 to <18 Years)0.6910.603 – 0.763
Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months Primary · At month 6 (Week 26) and 12 (Week 52) of on treatment period

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.

6 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)1.0001.000 – 1.000
Dabigatran Etexilate (2 to <12 Years)1.0001.000 – 1.000
Dabigatran Etexilate (12 to <18 Years)1.0001.000 – 1.000
12 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)1.0001.000 – 1.000
Dabigatran Etexilate (2 to <12 Years)1.0001.000 – 1.000
Dabigatran Etexilate (12 to <18 Years)1.0001.000 – 1.000
Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months Secondary · At month 6 (Week 26) and 12 (Week 52) of on treatment period

The event-free probability of PTS were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience PTS at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-PTS 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.

6 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)1.0001.000 – 1.000
Dabigatran Etexilate (2 to <12 Years)1.0001.000 – 1.000
Dabigatran Etexilate (12 to <18 Years)0.9790.935 – 0.993
12 months
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)1.0001.000 – 1.000
Dabigatran Etexilate (2 to <12 Years)1.0001.000 – 1.000
Dabigatran Etexilate (12 to <18 Years)0.9790.935 – 0.993
Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period Secondary · From first DE administration to 3 days of residual effect period after last DE administration, up to 52 weeks+ 3 days

Percentage of participants with dabigatran etexilate dose adjustments during on treatment period. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.

GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)66.7
Dabigatran Etexilate (2 to <12 Years)39.5
Dabigatran Etexilate (12 to <18 Years)21.1
Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) Secondary · At Visit 3 (day 4 after first dose of trial medication)
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)46.6± 18.1
Dabigatran Etexilate (2 to <12 Years)57.1± 70.4
Dabigatran Etexilate (12 to <18 Years)56.8± 64.6
Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) Secondary · 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.
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)49.1± 26.8
Dabigatran Etexilate (2 to <12 Years)57.3± 23.9
Dabigatran Etexilate (12 to <18 Years)59.0± 80.8
Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) Secondary · At Visit 3 (day 4 after first dose of trial medication)
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)52.7± 17.6
Dabigatran Etexilate (2 to <12 Years)64.3± 55.7
Dabigatran Etexilate (12 to <18 Years)69.5± 30.3
Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) Secondary · 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.
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)53.3± 19.4
Dabigatran Etexilate (2 to <12 Years)66.6± 23.6
Dabigatran Etexilate (12 to <18 Years)69.2± 28.7
Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) Secondary · At Visit 3 (day 4 after first dose of trial medication)
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)37.9± 19.5
Dabigatran Etexilate (2 to <12 Years)40.5± 14.6
Dabigatran Etexilate (12 to <18 Years)45.3± 17.4
Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) Secondary · 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.
GroupValue95% CI
Dabigatran Etexilate (0 to < 2 Years)40.0± 24.3
Dabigatran Etexilate (2 to <12 Years)46.0± 18.6
Dabigatran Etexilate (12 to <18 Years)43.4± 17.7

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose until last dose of study drug + 3 days of residual effect period, up to 52 weeks + 3 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dabigatran Etexilate (Treated Set)
Serious: 30/213 (14%)
Deaths: 0/213

Serious adverse events (46 terms)

ReactionSystemDabigatran Etexilate (Trea…
PneumoniaInfections and infestations
TonsillitisInfections and infestations
Deep vein thrombosisVascular disorders
Atrial flutterCardiac disorders
Cardiac failureCardiac disorders
MyocarditisCardiac disorders
Pericardial effusionCardiac disorders
Ventricular pre-excitationCardiac disorders
Congenital anomalyCongenital, familial and genetic disorders
Abdominal pain upperGastrointestinal disorders
GastritisGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
Chest painGeneral disorders
Oedema peripheralGeneral disorders
Hepatic vein stenosisHepatobiliary disorders
Catheter site infectionInfections and infestations
CellulitisInfections and infestations
EncephalitisInfections and infestations
GastroenteritisInfections and infestations
Pulpitis dentalInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
Animal biteInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Metal poisoningInjury, poisoning and procedural complications
Post procedural haematomaInjury, poisoning and procedural complications
Other adverse events (14 terms — click to expand)

ReactionSystemDabigatran Etexilate (Trea…
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Upper respiratory tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AlopeciaSkin and subcutaneous tissue disorders

Most-reported serious reactions: Pneumonia, Tonsillitis, Deep vein thrombosis, Atrial flutter, Cardiac failure, Myocarditis, Pericardial effusion, Ventricular pre-excitation.

Data from ClinicalTrials.gov NCT02197416 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children.
    Brandão LR, Albisetti M, Halton J, Bomgaars L, et al · · 2020 · cited 70× · PMID 31805182 · DOI 10.1182/blood.2019000998
  2. Management of thrombosis in children and neonates: practical use of anticoagulants in children.
    Monagle P, Newall F. · · 2018 · cited 63× · PMID 30504338 · DOI 10.1182/asheducation-2018.1.399
  3. Evidence Gaps in the Era of Non-Vitamin K Oral Anticoagulants.
    Aronis KN, Hylek EM. · · 2018 · cited 27× · PMID 29374049 · DOI 10.1161/jaha.117.007338
  4. Pharmacokinetic modeling and simulation support for age- and weight-adjusted dosing of dabigatran etexilate in children with venous thromboembolism.
    Röshammar D, Huang F, Albisetti M, Bomgaars L, et al · · 2021 · cited 14× · PMID 33636042 · DOI 10.1111/jth.15277
  5. Anticoagulant Effects of Dabigatran in Paediatric Patients Compared with Adults: Combined Data from Three Paediatric Clinical Trials.
    Maas H, Gropper S, Huang F, Stangier J, et al · · 2018 · cited 14× · PMID 30112751 · DOI 10.1055/s-0038-1668132
  6. Design and rationale for the DIVERSITY study: An open-label, randomized study of dabigatran etexilate for pediatric venous thromboembolism.
    Albisetti M, Biss B, Bomgaars L, Brandão LR, et al · · 2018 · cited 13× · PMID 30046738 · DOI 10.1002/rth2.12086
  7. Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism.
    Albisetti M, Schlosser A, Brueckmann M, Gropper S, et al · · 2018 · cited 10× · PMID 30046708 · DOI 10.1002/rth2.12053
  8. What did we learn (and did not learn) from the pediatric direct oral anticoagulant trials, and how might we better design pediatric anticoagulant trials in the future?
    Betensky M, Monagle P, Male C, Goldenberg NA. · · 2023 · cited 7× · PMID 37168398 · DOI 10.1016/j.rpth.2023.100140

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