Trial Outcomes & Findings for Open Label Study Comparing Efficacy and Safety of Dabigatran Etexilate to Standard of Care in Paediatric Patients With Venous Thromboembolism (VTE) (NCT NCT01895777)

Last Updated: 2020-07-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

267 participants

Primary outcome timeframe

From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.

Results posted on

2020-07-07

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Dabigatran Etexilate 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Study STARTED	177	90
Overall Study Treated	176	90
Overall Study COMPLETED	168	85
Overall Study NOT COMPLETED	9	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Dabigatran Etexilate 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Overall Study Adverse Event	1	2
Overall Study Lost to Follow-up	2	0
Overall Study Not treated	1	0
Overall Study Other reasons	3	2
Overall Study Non-compliance with the CTP	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran Etexilate n=177 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.	Total n=267 Participants Total of all reporting groups
Age, Continuous	11.1 Years STANDARD_DEVIATION 6.1 • n=5 Participants	11.0 Years STANDARD_DEVIATION 6.1 • n=7 Participants	11.1 Years STANDARD_DEVIATION 6.1 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	38 Participants n=7 Participants	134 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	52 Participants n=7 Participants	133 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	169 Participants n=5 Participants	86 Participants n=7 Participants	255 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	163 Participants n=5 Participants	82 Participants n=7 Participants	245 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.

Population: The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=177 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Composite Primary Endpoint Complete thrombus resolution	81 Participants	38 Participants
Composite Primary Endpoint Freedom from recurrent VTE	170 Participants	83 Participants
Composite Primary Endpoint Freedom from mortality related to VTE	177 Participants	89 Participants
Composite Primary Endpoint Composite endpoint met	81 Participants	38 Participants

SECONDARY outcome

Timeframe: From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.

Population: 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

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=176 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Freedom From Major Bleeding Events (MBEs)	0.977 Proportion of participants Interval 0.948 to 0.99	0.977 Proportion of participants Interval 0.929 to 0.993

SECONDARY outcome

Timeframe: From the time of randomisation until visit 3

Population: 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

Descriptive statistics for steady state plasma concentrations of total dabigatran etexilate at visit 3

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=139 Participants 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Steady State Plasma Concentrations of Total Dabigatran at Visit 3	79.8 nanogram per milliliter Geometric Coefficient of Variation 68.6 • Interval 68.6 to	—

SECONDARY outcome

Timeframe: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.

Descriptive statistics for steady state plasma concentrations of total dabigatran etexilate after at least 3 days following any dabigatran etexilate dose adjustment

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=49 Participants 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Steady State Plasma Concentrations After at Least 3 Days Following Any Dabigatran Etexilate Dose Adjustment	81.7 nanogram per milliliter Geometric Coefficient of Variation 54.7 • Interval 54.7 to	—

SECONDARY outcome

Timeframe: From first administration of trial medication until last administration of trial medication +6 days (residual effect period).

Population: 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

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

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=176 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Frequency of Dose Adjustment During the Treatment Phase With dose adjustment	63 Participants	56 Participants
Frequency of Dose Adjustment During the Treatment Phase With temporary interruption	25 Participants	6 Participants
Frequency of Dose Adjustment During the Treatment Phase Laboratory monitoring required	175 Participants	82 Participants

SECONDARY outcome

Timeframe: From first administration of trial medication until last administration of trial medication +6 days (residual effect period).

Population: 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

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=176 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
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	22 Participants	2 Participants

SECONDARY outcome

Timeframe: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.

Population: The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication

Freedom from thrombus progression at end of therapy compared with baseline, based on adjudication-confirmed data.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=177 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Freedom From Thrombus Progression at End of Therapy Compared With Baseline	148 Participants	73 Participants

SECONDARY outcome

Timeframe: From first administration of trial medication until last adminstration of trial medication +6 days (residual effect period). Up to 97 days.

Population: 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

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=176 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
All Bleeding Events Any bleeding	38 Participants	22 Participants
All Bleeding Events Major bleeding	4 Participants	2 Participants
All Bleeding Events CRNM bleeding	2 Participants	1 Participants
All Bleeding Events Minor bleeding	33 Participants	21 Participants
All Bleeding Events Major and CRNM bleeding	6 Participants	3 Participants

SECONDARY outcome

Timeframe: From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.

Population: 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

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=176 Participants 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).	Standard of Care n=90 Participants 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	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.

Population: The randomised set (RS) included all randomised patients in the treatment groups to which they were randomised, regardless whether they took trial medication

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=177 Participants 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).	Standard of Care n=90 Participants Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
All Components of the Primary Efficacy Endpoint Complete thrombus resolution by Day 84	81 Participants	38 Participants
All Components of the Primary Efficacy Endpoint Recurrent VTE by Day 84	7 Participants	7 Participants
All Components of the Primary Efficacy Endpoint VTE-related death by Day 84	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.

Population: 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

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=119 Participants 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules) Investigator questionnaire capsules	1.0 Score Standard Deviation 0.2	—
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules) Parents questionnaire capsules	1.0 Score Standard Deviation 0.0	—
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules) Patient questionnaire capsules	1.6 Score Standard Deviation 0.9	—

SECONDARY outcome

Timeframe: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.

Population: 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

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=42 Participants 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets) Investigator questionnaire pellets	1.2 Score Standard Deviation 0.6	—
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets) Parents questionnaire pellets	1.2 Score Standard Deviation 0.5	—

SECONDARY outcome

Timeframe: Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.

Population: 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

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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate n=14 Participants 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).	Standard of Care Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF) Investigator questionnaire flavoured OLF	1.6 Score Standard Deviation 0.8	—
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF) Investigator questionnaire unflavoured OLF	1.2 Score Standard Deviation 0.4	—
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF) Parents questionnaire flavoured OLF	1.4 Score Standard Deviation 0.5	—
Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF) Parents questionnaire unflavoured OLF	1.8 Score Standard Deviation 0.4	—

Adverse Events

Dabigatran Etexilate

Serious events: 25 serious events

Other events: 59 other events

Deaths: 2 deaths

Standard of Care

Serious events: 18 serious events

Other events: 16 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dabigatran Etexilate n=176 participants at risk 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).	Standard of Care n=90 participants at risk Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.
Gastrointestinal disorders Diarrhoea	5.1% 9/176 • Number of events 11 • 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. 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	1.1% 1/90 • Number of events 1 • 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. 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
Gastrointestinal disorders Dyspepsia	5.7% 10/176 • Number of events 10 • 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. 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	0.00% 0/90 • 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. 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
Gastrointestinal disorders Vomiting	8.0% 14/176 • Number of events 18 • 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. 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	1.1% 1/90 • Number of events 1 • 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. 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
General disorders Pyrexia	6.2% 11/176 • Number of events 12 • 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. 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	3.3% 3/90 • Number of events 3 • 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. 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
Infections and infestations Nasopharyngitis	6.2% 11/176 • Number of events 12 • 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. 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	7.8% 7/90 • Number of events 7 • 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. 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
Nervous system disorders Headache	9.7% 17/176 • Number of events 26 • 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. 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	4.4% 4/90 • Number of events 4 • 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. 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
Respiratory, thoracic and mediastinal disorders Epistaxis	4.5% 8/176 • Number of events 9 • 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. 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	6.7% 6/90 • Number of events 13 • 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. 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

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 8002430127

Email: [email protected]

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Principal investigator is a sponsor employee
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