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

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ClinicalTrials.gov Identifier: NCT01895777
Recruitment Status : Completed
First Posted : July 11, 2013
Results First Posted : July 7, 2020
Last Update Posted : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Venous Thromboembolism
Interventions Drug: dabigatran etexilate
Drug: standard of care
Enrollment 267
Recruitment Details A multi-centre, open-label, randomised, parallel-group, active-controlled, non-inferiority trial of dabigatran etexilate (DE) versus standard of care (SoC) in children from birth to less than 18 years of age.
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.

Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF). Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Period Title: Overall Study
Started 177 90
Treated 176 90
Completed 168 85
Not Completed 9 5
Reason Not Completed
Adverse Event             1             2
Lost to Follow-up             2             0
Not treated             1             0
Other reasons             3             2
Non-compliance with the CTP             2             1
Arm/Group Title Dabigatran Etexilate Standard of Care Total
Hide Arm/Group Description Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF). Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux. Total of all reporting groups
Overall Number of Baseline Participants 177 90 267
Hide Baseline Analysis Population Description
The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 177 participants 90 participants 267 participants
11.1  (6.1) 11.0  (6.1) 11.1  (6.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 90 participants 267 participants
Female
96
  54.2%
38
  42.2%
134
  50.2%
Male
81
  45.8%
52
  57.8%
133
  49.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 90 participants 267 participants
Hispanic or Latino
8
   4.5%
3
   3.3%
11
   4.1%
Not Hispanic or Latino
169
  95.5%
86
  95.6%
255
  95.5%
Unknown or Not Reported
0
   0.0%
1
   1.1%
1
   0.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 90 participants 267 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
10
   5.6%
3
   3.3%
13
   4.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   0.6%
3
   3.3%
4
   1.5%
White
163
  92.1%
82
  91.1%
245
  91.8%
More than one race
2
   1.1%
0
   0.0%
2
   0.7%
Unknown or Not Reported
1
   0.6%
2
   2.2%
3
   1.1%
1.Primary Outcome
Title Composite Primary Endpoint
Hide Description

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.

Time Frame From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 177 90
Measure Type: Count of Participants
Unit of Measure: Participants
Complete thrombus resolution
81
  45.8%
38
  42.2%
Freedom from recurrent VTE
170
  96.0%
83
  92.2%
Freedom from mortality related to VTE
177
 100.0%
89
  98.9%
Composite endpoint met
81
  45.8%
38
  42.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate, Standard of Care
Comments The primary analysis of the primary efficacy endpoint used the randomised set, following the intention-to-treat principle, based on adjudication-confirmed data. Age group was used as stratification factor using a Mantel-Haenszel type weighted average of differences.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin of 20%
Statistical Test of Hypothesis P-Value = 0.0001
Comments p-value for non-inferiority is actually <0.0001
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Rates
Estimated Value -0.038
Confidence Interval (2-Sided) 90%
-0.141 to 0.066
Estimation Comments Difference in rates (SOC - DE)
2.Secondary Outcome
Title Freedom From Major Bleeding Events (MBEs)
Hide Description 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.
Time Frame From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Proportion of participants
0.977
(0.948 to 0.990)
0.977
(0.929 to 0.993)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate, Standard of Care
Comments Time-to event endpoint using Kaplan-Meier estimates based on adjudication-confirmed data. Due to the low event rate of major bleeding, age group stratification was not considered.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Kaplan-Meier estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier estimate
Estimated Value 0.000
Confidence Interval (2-Sided) 90%
-0.032 to 0.032
Estimation Comments Kaplan-Meier estimate of rate difference.
3.Secondary Outcome
Title Steady State Plasma Concentrations of Total Dabigatran at Visit 3
Hide Description Descriptive statistics for steady state plasma concentrations of total dabigatran etexilate at visit 3
Time Frame From the time of randomisation until visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic set (PKS) included all patients treated with DE who had at least 1 evaluable PK measurement and had no protocol deviations relevant to the evaluation of PK endpoints. Only scheduled visits were considered
Arm/Group Title Dabigatran Etexilate
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Overall Number of Participants Analyzed 139
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter
79.8
(68.6% to N/A)
4.Secondary Outcome
Title Steady State Plasma Concentrations After at Least 3 Days Following Any Dabigatran Etexilate Dose Adjustment
Hide Description Descriptive statistics for steady state plasma concentrations of total dabigatran etexilate 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.
Hide Outcome Measure Data
Hide Analysis Population Description

The pharmacokinetic set (PKS) included all patients treated with DE who had at least

1 evaluable PK measurement and had no protocol deviations relevant to the evaluation of PK endpoints. Only scheduled visits were considered

Arm/Group Title Dabigatran Etexilate
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Overall Number of Participants Analyzed 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter
81.7
(54.7% to N/A)
5.Secondary Outcome
Title Frequency of Dose Adjustment During the Treatment Phase
Hide Description 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
Time Frame From first administration of trial medication until last administration of trial medication +6 days (residual effect period).
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 176 90
Measure Type: Count of Participants
Unit of Measure: Participants
With dose adjustment
63
  35.8%
56
  62.2%
With temporary interruption
25
  14.2%
6
   6.7%
Laboratory monitoring required
175
  99.4%
82
  91.1%
6.Secondary Outcome
Title 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
Hide Description

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.

Time Frame From first administration of trial medication until last administration of trial medication +6 days (residual effect period).
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 176 90
Measure Type: Count of Participants
Unit of Measure: Participants
22
  12.5%
2
   2.2%
7.Secondary Outcome
Title Freedom From Thrombus Progression at End of Therapy Compared With Baseline
Hide Description Freedom from thrombus progression at end of therapy compared with baseline, based on adjudication-confirmed data.
Time Frame From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 177 90
Measure Type: Count of Participants
Unit of Measure: Participants
148
  83.6%
73
  81.1%
8.Secondary Outcome
Title All Bleeding Events
Hide Description 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.
Time Frame From first administration of trial medication until last adminstration of trial medication +6 days (residual effect period). Up to 97 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 176 90
Measure Type: Count of Participants
Unit of Measure: Participants
Any bleeding
38
  21.6%
22
  24.4%
Major bleeding
4
   2.3%
2
   2.2%
CRNM bleeding
2
   1.1%
1
   1.1%
Minor bleeding
33
  18.8%
21
  23.3%
Major and CRNM bleeding
6
   3.4%
3
   3.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate, Standard of Care
Comments Any bleeding events was analysed as time-to-event endpoint using a stratified Cox proportional hazard model with treatment as a covariate in the model and age group as the stratification factor. A pooling of age groups was performed as no events were observed in certain age group.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.145
Confidence Interval (2-Sided) 90%
0.736 to 1.780
Estimation Comments [Not Specified]
9.Secondary Outcome
Title All-cause Mortality
Hide Description 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.
Time Frame From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 176 90
Measure Type: Number
Unit of Measure: Participants
0 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate, Standard of Care
Comments All-cause mortality was analyzed as time-to-event endpoint using a stratified Cox proportional hazard model with treatment as a covariate in the model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9976
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 69990000
Confidence Interval (2-Sided) 90%
0.000 to 999999999
Estimation Comments Upper Limit of the 90% confidence interval was not assessable
10.Secondary Outcome
Title All Components of the Primary Efficacy Endpoint
Hide Description 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.
Time Frame From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Number of Participants Analyzed 177 90
Measure Type: Count of Participants
Unit of Measure: Participants
Complete thrombus resolution by Day 84
81
  45.8%
38
  42.2%
Recurrent VTE by Day 84
7
   4.0%
7
   7.8%
VTE-related death by Day 84
0
   0.0%
1
   1.1%
11.Secondary Outcome
Title Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules)
Hide Description

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.

Time Frame Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules.
Overall Number of Participants Analyzed 119
Mean (Standard Deviation)
Unit of Measure: Score
Investigator questionnaire capsules Number Analyzed 111 participants
1.0  (0.2)
Parents questionnaire capsules Number Analyzed 14 participants
1.0  (0.0)
Patient questionnaire capsules Number Analyzed 92 participants
1.6  (0.9)
12.Secondary Outcome
Title Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets)
Hide Description

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.

Time Frame Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets.
Overall Number of Participants Analyzed 42
Mean (Standard Deviation)
Unit of Measure: Score
Investigator questionnaire pellets Number Analyzed 42 participants
1.2  (0.6)
Parents questionnaire pellets Number Analyzed 33 participants
1.2  (0.5)
13.Secondary Outcome
Title Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF)
Hide Description

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.

Time Frame Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.
Hide Outcome Measure Data
Hide Analysis Population Description
The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
Arm/Group Title Dabigatran Etexilate
Hide Arm/Group Description:
Oral administration of dabigatran etexilate (DE) twice daily. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: Score
Investigator questionnaire flavoured OLF Number Analyzed 7 participants
1.6  (0.8)
Investigator questionnaire unflavoured OLF Number Analyzed 5 participants
1.2  (0.4)
Parents questionnaire flavoured OLF Number Analyzed 7 participants
1.4  (0.5)
Parents questionnaire unflavoured OLF Number Analyzed 5 participants
1.8  (0.4)
Time Frame For DE patients all AEs recorded between first dabigatran etexilate (DE) intake until 6 days after the last administration of dabigatran etexilate. For patients in standard of care arm, all AEs occurred between the first drug intake of standard of care (SOC) until 6 days after the last administration of any standard of care. The Open-label treatment period with DE or SOC is from vist 2 defined as day 0 up to 84 days.
Adverse Event Reporting Description The treated set (TS) includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of trial medication
 
Arm/Group Title Dabigatran Etexilate Standard of Care
Hide Arm/Group Description Oral administration of dabigatran etexilate (DE) twice daily. Patients aged ≥8 years: age- and weight-adjusted DE dosing via capsules using 50 milligram (mg), 75 mg, 110 mg, and 150 mg capsules. Patients aged <8 years or for patients who cannot take capsules even if older than 8 (but <12 years of age): age- and weight-adjusted dosing via DE pellets. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF). Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
All-Cause Mortality
Dabigatran Etexilate Standard of Care
Affected / at Risk (%) Affected / at Risk (%)
Total   2/176 (1.14%)      2/90 (2.22%)    
Hide Serious Adverse Events
Dabigatran Etexilate Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/176 (14.20%)      18/90 (20.00%)    
Blood and lymphatic system disorders     
Anaemia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Febrile neutropenia  1  3/176 (1.70%)  3 0/90 (0.00%)  0
Pancytopenia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Sickle cell anaemia with crisis  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Thrombocytopenia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Cardiac disorders     
Cardiac arrest  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Cardiac failure  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Tachycardia  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Eye disorders     
Papilloedema  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Gastrointestinal disorders     
Abdominal pain  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Abdominal pain upper  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Gastrointestinal haemorrhage  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Haematochezia  1  2/176 (1.14%)  3 1/90 (1.11%)  1
Haemorrhoids  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Pancreatitis chronic  1  1/176 (0.57%)  2 0/90 (0.00%)  0
Peritoneal haemorrhage  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Proctitis haemorrhagic  1  1/176 (0.57%)  2 0/90 (0.00%)  0
General disorders     
Implant site necrosis  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Infections and infestations     
Erysipelas  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Gastroenteritis  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Gastroenteritis rotavirus  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Influenza  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Mastoiditis  1  1/176 (0.57%)  1 1/90 (1.11%)  1
Meningitis herpes  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Osteomyelitis  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Pneumonia viral  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Sepsis  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Septic shock  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Staphylococcal sepsis  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Wound sepsis  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Injury, poisoning and procedural complications     
Procedural haemorrhage  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Investigations     
Blood creatinine increased  1  1/176 (0.57%)  1 1/90 (1.11%)  1
Metabolism and nutrition disorders     
Dehydration  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Diabetic ketoacidosis  1  1/176 (0.57%)  2 0/90 (0.00%)  0
Hyperglycaemia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Hypoalbuminaemia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Hypoproteinaemia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Myositis  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Pain in extremity  1  1/176 (0.57%)  1 1/90 (1.11%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Nervous system disorders     
Haemorrhage intracranial  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Hepatic encephalopathy  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Tension headache  1  0/176 (0.00%)  0 1/90 (1.11%)  2
Psychiatric disorders     
Suicidal ideation  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Asthmatic crisis  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Dyspnoea  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Pulmonary embolism  1  0/176 (0.00%)  0 2/90 (2.22%)  2
Respiratory failure  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Tachypnoea  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Vascular disorders     
Deep vein thrombosis  1  2/176 (1.14%)  2 3/90 (3.33%)  3
Embolism venous  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Haemorrhagic infarction  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Post thrombotic syndrome  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Shock  1  0/176 (0.00%)  0 1/90 (1.11%)  1
Takayasu's arteritis  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Thrombophlebitis superficial  1  1/176 (0.57%)  1 0/90 (0.00%)  0
Thrombosis  1  0/176 (0.00%)  0 1/90 (1.11%)  1
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dabigatran Etexilate Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   59/176 (33.52%)      16/90 (17.78%)    
Gastrointestinal disorders     
Diarrhoea  1  9/176 (5.11%)  11 1/90 (1.11%)  1
Dyspepsia  1  10/176 (5.68%)  10 0/90 (0.00%)  0
Vomiting  1  14/176 (7.95%)  18 1/90 (1.11%)  1
General disorders     
Pyrexia  1  11/176 (6.25%)  12 3/90 (3.33%)  3
Infections and infestations     
Nasopharyngitis  1  11/176 (6.25%)  12 7/90 (7.78%)  7
Nervous system disorders     
Headache  1  17/176 (9.66%)  26 4/90 (4.44%)  4
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  8/176 (4.55%)  9 6/90 (6.67%)  13
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 8002430127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01895777    
Other Study ID Numbers: 1160.106
2013-002114-12 ( EudraCT Number )
First Submitted: July 4, 2013
First Posted: July 11, 2013
Results First Submitted: May 12, 2020
Results First Posted: July 7, 2020
Last Update Posted: July 7, 2020