Open Label Study Comparing Efficacy and Safety of Dabigat... | NCT01895777

NCT01895777

ID	Type	Description	Link
2013-002114-12	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
dabigatran etexilate	Experimental	Dabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months	Drug: dabigatran etexilate
standard of care	Active Comparator	Low molecular weight heparin, vitamin K antagonist or fondaparinux prescribed in an open label fashion for 3 months (these medications will not supplied in this study as IMP)	Drug: standard of care

Interventions

Name	Type	Description	Arm Group Labels	Other Names
dabigatran etexilate	Drug	Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation	dabigatran etexilate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Composite Primary Endpoint	The primary endpoint was the combined endpoint of the proportions of patients with: Complete thrombus resolution Freedom from recurrent VTE Freedom from mortality related to VTE. The events outlined in the above combined primary endpoint were assessed by radiologists or other such qualified clinicians using an appropriate method such as ultrasound, echocardiography, venography, or CT scan, based on the location of the thrombus and the test used to perform the baseline assessment. The primary efficacy endpoint contained 3 components. Each component was evaluated separately, and only if the criteria for all 3 components were satisfied, the primary endpoint was considered achieved.	From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.

Secondary Outcomes

Measure	Description	Time Frame
Freedom From Major Bleeding Events (MBEs)	Freedom from major bleeding events (MBEs), defined as either fatal bleeding, clinically overt bleeding associated with a decrease in haemoglobin of at least 20 g/L in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial or otherwise involves the central nervous system, or bleeding that requires intervention in an operating suite.	From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Male or female subjects 0 to less than 18 years of age at the time of informed consent / assent
Documented diagnosis of clinically stable VTE (e.g. DVT, PE, central line thrombosis, sinus vein thrombosis) per investigator judgment, initially treated (minimum of 5 to 7 days, but not longer than 21 days) with parenteral anticoagulation therapy, such as unfractionated heparin (UFH) or a low molecular weight heparin (LMWH).
Clinical indication for at least 3 month of treatment with anticoagulants for the VTE episode defined under the above inclusion criterion.
Written informed consent provided by the patient's parent or legal guardian and assent provided by the patient (if applicable) at the time of informed consent form (ICF) signature according to local regulations.

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 a medically accepted contraceptive method per local guidelines. Acceptable methods of birth control must be used in a correct and consistent manner
Patients in stratum 3 (0 to < 2 years) with gestational age at birth < 37 weeks or with body weight lower than the 3rd percentile
Anemia (hemoglobin < 80g/L) or thrombocytopenia (platelet count < 80 x 109/L) at screening. Transfusions during the screening period are allowed, provided that a satisfactory hemoglobin or platelet level is attained prior to visit 2
Patients who have taken prohibited or restricted medication within one week of the first dose of study medication other than medication for prior VTE treatment and P-glycoprotein inhibitors..
Patients who have received an investigational drug in the past 30 days prior to screening
Patients who are allergic/sensitive to any component of the study medication including solvent
Patients or parents/legal guardians considered unreliable to participate in the trial per investigator judgment or any condition which would present a safety hazard to the patient based on investigator judgment
Patients or parents/legal guardians who are unwilling or unable to undergo or permit repeat of the baseline imaging tests required to confirm thrombus resolution at study day 84 (or eEOT, whichever comes first) or in whom repeating such imaging tests at these pre-specified time points may not be medically in the patient's best interest. Examples may include unwarranted radiation exposure as a result of a repeat CT scan at day 84 for a patient with an isolated case of pulmonary embolism evaluated at baseline solely by a CT scan. In such cases, the baseline radiological assessment (e.g. CT) may be supplemented with an acceptable non-radiological assessment at baseline (e.g. MRI) which could then be repeated at day 84 hence alleviating any potential unwarranted radiation exposure.
Further exclusion criteria apply

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of California Davis		Sacramento	California	95817	United States
University of Miami

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38348778	Derived	Albisetti M, Tartakovsky I, Halton J, Bomgaars L, Chalmers E, Mitchell LG, Luciani M, Nurmeev I, Gorbatikov K, Miede C, Brueckmann M, Brandao LR; Study Investigators. Dabigatran for Treatment and Secondary Prevention of Venous Thromboembolism in Pediatric Congenital Heart Disease. J Am Heart Assoc. 2024 Feb 20;13(4):e028957. doi: 10.1161/JAHA.122.028957. Epub 2024 Feb 13.
36150047

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 6, 2019	May 11, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

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 Information

ID	Title	Description
BG000	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).
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00011.1± 6.1 BG00111.0± 6.1 BG00211.1± 6.1

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00096 BG00138 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0008 BG0013 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Composite Primary Endpoint

The primary endpoint was the combined endpoint of the proportions of patients with:

Complete thrombus resolution
Freedom from recurrent VTE
Freedom from mortality related to VTE. The events outlined in the above combined primary endpoint were assessed by radiologists or other such qualified clinicians using an appropriate method such as ultrasound, echocardiography, venography, or CT scan, based on the location of the thrombus and the test used to perform the baseline assessment.

The primary efficacy endpoint contained 3 components. Each component was evaluated separately, and only if the criteria for all 3 components were satisfied, the primary endpoint was considered achieved.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	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.

Units	Counts
Participants	OG000177 OG00190

Title

Denominators

Categories

Complete thrombus resolution

Title	Measurements
	OG00081 OG00138

Freedom from recurrent VTE

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Cochran-Mantel-Haenszel		= 0.0001	p-value for non-inferiority is actually <0.0001	Difference in Rates	-0.038			2-Sided	90	-0.141	0.066			Difference in rates (SOC - DE)		Non-Inferiority

Secondary

Freedom From Major Bleeding Events (MBEs)

Freedom from major bleeding events (MBEs), defined as either fatal bleeding, clinically overt bleeding associated with a decrease in haemoglobin of at least 20 g/L in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial or otherwise involves the central nervous system, or bleeding that requires intervention in an operating suite.

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

Posted

Number

90% Confidence Interval

Proportion of participants

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

ID	Title	Description
OG000	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).
OG001	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.

Secondary

Steady State Plasma Concentrations of Total Dabigatran at Visit 3

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

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

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

From the time of randomisation until visit 3

ID	Title	Description
OG000	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).

Units	Counts
Participants	OG000

Secondary

Steady State Plasma Concentrations After at Least 3 Days Following Any Dabigatran Etexilate Dose Adjustment

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

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

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

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

ID	Title	Description
OG000	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).

Units	Counts
Participants

Secondary

Frequency of Dose Adjustment During the Treatment Phase

Frequency of dose adjustments (i.e. number of patients with dose adjustment), temporary and permanent discontinuation from therapy, and number of patients with laboratory monitoring requirements for dose

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	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.

Secondary

Frequency of Patients Switching the Type of Anti-coagulation Therapy Including Dabigatran Etexilate to Standard of Care Treatment and Switching From One Standard of Care Treatment to Another

Frequency of patients switching the type of anti-coagulation therapy including Dabigatran etexilate (DE) to standard of care (SoC) treatment and switching from one standard of care treatment to another.

For DE arm, only the switch from DE to SoC was counted, while for the SoC arm, all switches among SoC treatments were counted.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	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.

Secondary

Freedom From Thrombus Progression at End of Therapy Compared With Baseline

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

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	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.

Units

Secondary

All Bleeding Events

The number of participants with bleeding events includes major bleeding events (MBEs), clinically relevant non-major (CRNM) bleeding, minor bleeding events, any bleeding events, and the numbers of the combined endpoint of major and CRNM bleeding events was presented, based on adjudication-confirmed data.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	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.

Secondary

All-cause Mortality

Patients being alive at the end of observational period will be censored for all-cause mortality at the date of patients' last date known to be alive, or the date of data cut-off whichever comes first.

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

Posted

Number

Participants

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

ID	Title	Description
OG000	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).
OG001	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.

Secondary

All Components of the Primary Efficacy Endpoint

Patients with VTE-related death occurring between randomisation to Day 84 + 7 days were considered as not meeting the endpoint. The presence of recurrent VTE(s) was examined throughout the trial, and only the date of first occurrence was used for analysis. Assessment of index VTE status (best overall response) was scheduled on Day 84 ± 7 days (Visit 8) for patients who were alive without an early consent withdraw. In the case a Patient discontinued trial medication prematurely due to any reason the index VTE assessment took place at the early end of treatment visit.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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).
OG001	Standard of Care

Secondary

Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules)

Acceptability was defined as the overall ability and willingness of the patient to use the medicinal product. Questions regarding acceptability were to be answered by the patient and/or parent/caregiver (as applicable) and by the investigator/site staff.

Investigator questionnaire capsules: What is your impression about the patient's acceptability of DE intake? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).

Parents questionnaire capsules: How acceptable was the DE treatment for the child? The score is 1 (good), 2 (satisfactory), 3 (not satisfactory) and 4 (bad).

Patients questionnaire capsules: Was taking the study capsules easy or difficult? The score is 1 (Very easy), 2 (easy), 3 (neither easy nor difficult), 4 (difficult) and 5 (very difficult).

Scores refers to the end of treatment.

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

Posted

Mean

Standard Deviation

Score

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

ID	Title	Description
OG000	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.

Units

Secondary

Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets)

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.

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

Posted

Mean

Standard Deviation

Score

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

ID	Title	Description
OG000	Dabigatran Etexilate	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.

Units	Counts
Participants

Secondary

Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF)

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.

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

Posted

Mean

Standard Deviation

Score

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

ID	Title	Description
OG000	Dabigatran Etexilate	Oral administration of dabigatran etexilate (DE) twice daily. Patients aged <12 months: age- and weight-adjusted dosing via DE oral liquid formulation (OLF).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).	2	176	25	176	59	176
EG001	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.	2	90	18	90	16	90

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0003 events3 affected176 at risk EG0010 events0 affected90 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Sickle cell anaemia with crisis	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Cardiac arrest	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Cardiac failure	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Tachycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Papilloedema	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 events2 affected176 at risk EG0011 events1 affected90 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 events1 affected176 at risk EG0010 events0 affected90 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Proctitis haemorrhagic	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 events1 affected176 at risk EG0010 events0 affected90 at risk
Implant site necrosis	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Erysipelas	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Gastroenteritis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Gastroenteritis rotavirus	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Influenza	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Mastoiditis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected90 at risk
Meningitis herpes	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Osteomyelitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Pneumonia viral	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Septic shock	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Wound sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Blood creatinine increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected90 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 events1 affected176 at risk EG0010 events0 affected90 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0011 events1 affected90 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Tension headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0012 events1 affected90 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0012 events2 affected90 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected176 at risk EG0013 events3 affected90 at risk
Embolism venous	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Haemorrhagic infarction	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Post thrombotic syndrome	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Shock	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk
Takayasu's arteritis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Thrombophlebitis superficial	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected176 at risk EG0010 events0 affected90 at risk
Thrombosis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected176 at risk EG0011 events1 affected90 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00011 events9 affected176 at risk EG0011 events1 affected90 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00010 events10 affected176 at risk EG0010 events0 affected90 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00018 events14 affected176 at risk EG0011 events1 affected90 at risk
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG00012 events11 affected176 at risk EG0013 events3 affected90 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG00012 events11 affected176 at risk EG0017 events7 affected90 at risk
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG00026 events17 affected176 at risk EG0014 events4 affected90 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0009 events8 affected176 at risk EG00113 events6 affected90 at risk

ID	Term
D054556	Venous Thromboembolism

ID	Term
D000069604	Dabigatran
D059039	Standard of Care

Ancestor Terms

ID	Term
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D019984	Quality Indicators, Health Care
D011787	Quality of Health Care
D006298	Health Services Administration
D017530	Health Care Quality, Access, and Evaluation

Non-inferiority margin of 20%

Units	Counts
Participants	OG000176 OG00190

Investigators decided on SoC treatment at time of randomisation: either low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) or fondaparinux.

Units	Counts
Participants	OG00014

ID	Term
D013923	Thromboembolism
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases