Secondary Prevention, Venous Thromboembolism
Conditions
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.
Interventions
DRUGdabigatran etexilate
Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 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. |
| Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 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. |
| Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 | 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. |
| Central Measurement of Diluted Thrombin Time (dTT) 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 Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 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. | — |
| Central Measurement of Ecarin Clotting Time (ECT) 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. | — |
| 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 | 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. |
| 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) | — |
Countries
Austria, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Lithuania, Mexico, Norway, Russia, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
This open label, single arm prospective cohort study was designed to assess the safety of dabigatran etexilate (DE) for secondary prevention of paediatric venous thromboembolism (VTE) with 12-month (365 days) treatment period followed by 28 days end of treatment follow-up. Results of participants were reported via 3 mutually exclusive age groups.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. 1 enrolled subject was withdrawn before treated due to unable to swallow the capsules.
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Etexilate (0 to < 2 Years) Single oral dose of dabigatran etexilate (DE) oral liquid formulation (OLF) ranging from 6.25 milligram(mg) to 143.75 mg was administrated twice daily in the morning and evening for participants aged less than 12 months.
Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years.
Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and \<250 nanogram(ng)/ milliliter (mL). The DE dose limit was 22.2 mg/kilogram (kg)/day.The maximal DE single dose was 330 mg.
This arm includes participants aged between 0 to \<2 years. | 9 |
| Dabigatran Etexilate (2 to <12 Years) Single oral dose of DE pellets ranging from 20mg to 330mg was administrated twice daily in the morning and evening for participants aged less than 8 years and who cannot take capsules between 8 and \<12 years.
Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years.
Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and \<250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg.
This arm includes participants aged between 2 to \< 12 years. | 43 |
| Dabigatran Etexilate (12 to <18 Years) Single oral dose of DE capsule ranging from 50 mg to 330mg was administrated twice daily in the morning and evening for participants aged at least 8 years.
Dosage of DE was adjusted by age and weight of participants intending to achieve trough plasma dabigatran concentrations between 50 and \<250 ng/mL. The DE dose limit was 22.2 mg/kg/day.The maximal DE single dose was 330 mg.
This arm includes participants aged between 12 to \<18 years. | 161 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Other reasons | 0 | 2 | 5 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Dabigatran Etexilate (0 to < 2 Years) | Dabigatran Etexilate (2 to <12 Years) | Dabigatran Etexilate (12 to <18 Years) | Total |
|---|---|---|---|---|
| Age, Continuous | 0.6 Years STANDARD_DEVIATION 0.5 | 6.8 Years STANDARD_DEVIATION 3.1 | 15.1 Years STANDARD_DEVIATION 1.6 | 12.8 Years STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 7 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 41 Participants | 153 Participants | 203 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 37 Participants | 149 Participants | 194 Participants |
| Sex: Female, Male Female | 4 Participants | 22 Participants | 70 Participants | 96 Participants |
| Sex: Female, Male Male | 5 Participants | 21 Participants | 91 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 213 |
| other Total, other adverse events | 113 / 213 |
| serious Total, serious adverse events | 30 / 213 |
Outcome results
Primary
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.
Time frame: At month 6 (Week 26) and month 12 (Week 52) of on treatment period
Population: The treated set (TS) included all patients who were dispensed trial medication and had taken at least 1 dose of investigational treatment, which was used to assess safety endpoints, demographics and baseline characteristics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 6 months | 0.889 Probability |
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 12 months | 0.889 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 6 months | 0.894 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 12 months | 0.831 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 6 months | 0.753 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months | 12 months | 0.691 Probability |
Primary
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.
Time frame: At month 6 (Week 26) and 12 (Week 52) of on treatment period
Population: The treated set (TS) included all patients who were dispensed trial medication and had taken at least 1 dose of investigational treatment, which was used to assess safety endpoints, demographics and baseline characteristics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 12 months | 1.000 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 12 months | 1.000 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months | 12 months | 1.000 Probability |
Primary
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.
Time frame: At month 6 (Week 26) and 12 (Week 52) of on treatment period
Population: The treated set (TS) included all patients who were dispensed trial medication and had taken at least 1 dose of investigational treatment, which was used to assess safety endpoints, demographics and baseline characteristics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 12 months | 1.000 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 12 months | 1.000 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 6 months | 0.979 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months | 12 months | 0.979 Probability |
Secondary
Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)
Time frame: 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.
Population: The PD set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 49.1 Second (s) | Standard Deviation 26.8 |
| Dabigatran Etexilate (2 to <12 Years) | Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 57.3 Second (s) | Standard Deviation 23.9 |
| Dabigatran Etexilate (12 to <18 Years) | Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 59.0 Second (s) | Standard Deviation 80.8 |
Secondary
Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)
Time frame: At Visit 3 (day 4 after first dose of trial medication)
Population: The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with non-missing endpoint values were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 46.6 Second (s) | Standard Deviation 18.1 |
| Dabigatran Etexilate (2 to <12 Years) | Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 57.1 Second (s) | Standard Deviation 70.4 |
| Dabigatran Etexilate (12 to <18 Years) | Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 56.8 Second (s) | Standard Deviation 64.6 |
Secondary
Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)
Time frame: 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.
Population: The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 40.0 Second (s) | Standard Deviation 24.3 |
| Dabigatran Etexilate (2 to <12 Years) | Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 46.0 Second (s) | Standard Deviation 18.6 |
| Dabigatran Etexilate (12 to <18 Years) | Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 43.4 Second (s) | Standard Deviation 17.7 |
Secondary
Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)
Time frame: At Visit 3 (day 4 after first dose of trial medication)
Population: The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 37.9 Second (s) | Standard Deviation 19.5 |
| Dabigatran Etexilate (2 to <12 Years) | Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 40.5 Second (s) | Standard Deviation 14.6 |
| Dabigatran Etexilate (12 to <18 Years) | Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 45.3 Second (s) | Standard Deviation 17.4 |
Secondary
Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)
Time frame: 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.
Population: The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 53.3 Second (s) | Standard Deviation 19.4 |
| Dabigatran Etexilate (2 to <12 Years) | Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 66.6 Second (s) | Standard Deviation 23.6 |
| Dabigatran Etexilate (12 to <18 Years) | Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment) | 69.2 Second (s) | Standard Deviation 28.7 |
Secondary
Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)
Time frame: At Visit 3 (day 4 after first dose of trial medication)
Population: The pharmacodynamics (PD) set (PDS) included all treated patients who provided at least one evaluable PD observation and had no protocol deviations relevant to the evaluation of PD endpoints. Only those with DE dose adjustment and non-missing endpoint values were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 52.7 Second (s) | Standard Deviation 17.6 |
| Dabigatran Etexilate (2 to <12 Years) | Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 64.3 Second (s) | Standard Deviation 55.7 |
| Dabigatran Etexilate (12 to <18 Years) | Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses) | 69.5 Second (s) | Standard Deviation 30.3 |
Secondary
Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months
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.
Time frame: At month 6 (Week 26) and 12 (Week 52) of on treatment period
Population: The treated set (TS) included all patients who were dispensed trial medication and had taken at least 1 dose of investigational treatment, which was used to assess safety endpoints, demographics and baseline characteristics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (0 to < 2 Years) | Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months | 12 months | 1.000 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months | 6 months | 1.000 Probability |
| Dabigatran Etexilate (2 to <12 Years) | Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months | 12 months | 1.000 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months | 6 months | 0.979 Probability |
| Dabigatran Etexilate (12 to <18 Years) | Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months | 12 months | 0.979 Probability |
Secondary
Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period
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.
Time frame: From first DE administration to 3 days of residual effect period after last DE administration, up to 52 weeks+ 3 days
Population: The treated set (TS) included all patients who were dispensed trial medication and had taken at least 1 dose of investigational treatment, which was used to assess safety endpoints, demographics and baseline characteristics.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabigatran Etexilate (0 to < 2 Years) | Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period | 66.7 Percentage of participants |
| Dabigatran Etexilate (2 to <12 Years) | Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period | 39.5 Percentage of participants |
| Dabigatran Etexilate (12 to <18 Years) | Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period | 21.1 Percentage of participants |