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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01895777
• Collaborator: (none)
• Enrollment: 267
• Locations: 65
• Arms: 2
• Actual Duration (Months): 73.6
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main objectives of this large phase IIb/III paediatric study are to assess the efficacy and safety of dabigatran etexilate relative to standard of care and to document the appropriateness of the proposed dabigatran etexilate dosing algorithm for use in patients from birth to less than 18 years of age.

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism	Drug: dabigatran etexilate; Drug: standard of care	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 267 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Randomized, Parallel-group, Active-controlled, Multi-centre Non-inferiority Study of Dabigatran Etexilate Versus Standard of Care for Venous Thromboembolism Treatment in Children From Birth to Less Than 18 Years of Age
• Actual Study Start Date: Sep 25, 2013
• Actual Primary Completion Date: Oct 16, 2019
• Actual Study Completion Date: Nov 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dabigatran etexilate Dabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months	Drug: dabigatran etexilate; Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation
Active Comparator: standard of care 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; 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)

Outcome Measures

Primary Outcome Measures

1. Composite Primary Endpoint [From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.]

   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.

Secondary Outcome Measures

1. Freedom From Major Bleeding Events (MBEs) [From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.]

   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.

2. Steady State Plasma Concentrations of Total Dabigatran at Visit 3 [From the time of randomisation until visit 3]

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

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

4. Frequency of Dose Adjustment During the Treatment Phase [From first administration of trial medication until last administration of trial medication +6 days (residual effect period).]

   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

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

   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.

6. Freedom From Thrombus Progression at End of Therapy Compared With Baseline [From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.]

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

7. All Bleeding Events [From first administration of trial medication until last adminstration of trial medication +6 days (residual effect period). Up to 97 days.]

   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.

8. All-cause Mortality [From first administration of trial medication until last administration of trial medication +6 days (residual effect period). Up to 97 days.]

   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.

9. All Components of the Primary Efficacy Endpoint [From the time of randomisation until Week 12, 84 days after randomisation including a visit window of 7 days.]

   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.

10. Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Capsules) [Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.]

    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.

11. Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Pellets) [Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.]

    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.

12. Assessment of the Acceptability of an Age-appropriate Formulation at End of Therapy (Oral Liquid Formulation - OLF) [Assessment at the last study visit at day 84 (+- 7 days), or at day of early termination.]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis	Sacramento	California	United States	95817
2	University of Miami	Miami	Florida	United States	33136
3	St. Joseph's Children's Hospital	Tampa	Florida	United States	33607
4	Blank Children's Hospital	Des Moines	Iowa	United States	50309
5	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
6	Boston Children's Hospital	Boston	Massachusetts	United States	02115
7	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
8	University of Virginia Health System	Charlottesville	Virginia	United States	22908
9	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
10	Hospital General de Niños Pedro de Elizalde	Caba		Argentina	C1270AAN
11	Medical University of Innsbruck	Innsbruck		Austria	6020
12	AKH - Medical University of Vienna	Wien		Austria	1090
13	Brussels - UNIV Saint-Luc	Bruxelles		Belgium	1200
14	UNIV UZ Gent	Gent		Belgium	9000
15	UZ Leuven	Leuven		Belgium	3000
16	HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas	Campinas		Brazil	13059-740
17	Faculdade de Ciencias Medicas da UNICAMP	Campinas		Brazil	13083-970
18	PenSI - Pesquisa e Ensino em Saude Infantil	Sao Paulo		Brazil	01227-200
19	Instituto de Crianca / Hospital das Clínicas-FMUSP	Sao Paulo		Brazil	05403-000
20	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
21	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
22	CHU Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
23	University Hospital Brno	Brno		Czechia	61300
24	General Univ.hosp Hradec Kralove	Hradec Kralove		Czechia	500 05
25	University Hospital Olomouc	Olomouc		Czechia	77900
26	University Hospital Ostrava	Ostrava		Czechia	70852
27	University Hospital Plzen, Plzen-Lochotin	Plzen-Lochotin		Czechia	304 60
28	University Hospital Motol	Prague		Czechia	15006
29	Rigshospitalet, København, Børneonkologisk Afsnit 5002	Copenhagen		Denmark	2100
30	TaUH, Pediatric Early Phase Trial Unit	Tampere		Finland	33520
31	HOP de la Cavale Blanche	Brest cedex		France	29609
32	Universitätsklinikum Essen AöR	Essen		Germany	45147
33	Universitätsklinikum Münster	Münster		Germany	48149
34	"Aghia Sophia" Children's Hospital	Athens		Greece	11527
35	University Debrecen Hospital	Debrecen		Hungary	4032
36	Shaare Zedek Medical Center, Jerusalem 91031	Jerusalem		Israel	9103102
37	Università degli Studi "La Sapienza"	Roma		Italy	00161
38	Ospedale Infantile Regina Margherita	Torino		Italy	10126
39	Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius	Vilnius		Lithuania	08406
40	Instituto Nacional de Pediatría	México D.F		Mexico	04530
41	Hospital Universitario Dr Jose Eleuterio Gonzalez	Nuevo León		Mexico	64460
42	Haukeland Universitetssykehus	Bergen		Norway	N-5021
43	Oslo Universitetssykehus HF, Rikshospitalet	Oslo		Norway	N-0372
44	Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan	Kazan		Russian Federation	420138
45	Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo	Kemerovo		Russian Federation	650002
46	Izmilovskaya Child City ClinHosp,Haematological Dept, Moscow	Moscow		Russian Federation	105077
47	Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol	Moscow		Russian Federation	125373
48	St.Petersburg State Pediatric Univ.Ministry of Healthcare RF	St. Petersburg		Russian Federation	194100
49	Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery	Tyument		Russian Federation	625023
50	Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg	Yekaterinburg		Russian Federation	620134
51	Hospital Infantil Universitario Niño Jesus	Madrid		Spain	28009
52	Sahlgrenska US, Göteborg	Göteborg		Sweden	41345
53	Karolinska Univ. sjukhuset	Solna		Sweden	171 65
54	Universitäts-Kinderspital	Zürich		Switzerland	8032
55	Taichung Veterans General Hospital	Taichung		Taiwan	407
56	King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
57	Cukurova Universitesi Tip Fakultesi Cocuk Sagligi	Adana		Turkey	1330
58	Hacettepe Universitesi Tip Fakultesi	Ankara		Turkey	06100
59	Akdeniz Universitesi Tip Fakultesi	Antalya		Turkey	7058
60	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul		Turkey	34098
61	Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH	Istanbul		Turkey	34303
62	Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali	Izmir		Turkey	35040
63	Necmettin Erbakan Universitesi Meram Tip Fakultesi	Konya		Turkey	42080
64	Reg.Children Hosp.Dnipropetrovsk	Dnipropetrovsk		Ukraine	49100
65	Reg.Children Hosp,Vinnytsia	Vinnytsya		Ukraine	21029

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Study Protocol - Feb 6, 2019
• Statistical Analysis Plan - Mar 25, 2019

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01895777
• Other Study ID Numbers: 1160.106; 2013-002114-12
• First Posted: Jul 11, 2013
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Thromboembolism; Venous Thromboembolism; Dabigatran

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	Dabigatran Etexilate	Standard of Care	Total
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 Participants	177	90	267
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	11.1 (6.1)	11.0 (6.1)	11.1 (6.1)
Sex: Female, Male (Count of Participants)
Female	96 54.2%	38 42.2%	134 50.2%
Male	81 45.8%	52 57.8%	133 49.8%
Ethnicity (NIH/OMB) (Count of 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%	1 1.1%	1 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	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%
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%	2 0.7%
Unknown or Not Reported	1 0.6%	2 2.2%	3 1.1%

Outcome Measures

1. Primary Outcome

Title	Composite Primary Endpoint
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.

Outcome Measure Data

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
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.
Measure Participants	177	90
Complete thrombus resolution	81 45.8%	38 42.2%
Freedom from recurrent VTE	170 96%	83 92.2%
Freedom from mortality related to VTE	177 100%	89 98.9%
Composite endpoint met	81 45.8%	38 42.2%

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
Method of Estimation	Estimation Parameter	Difference in Rates
	Estimated Value	-0.038
	Confidence Interval	(2-Sided) 90%; -0.141 to 0.066
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in rates (SOC - DE)

2. Secondary Outcome

Title	Freedom From Major Bleeding Events (MBEs)
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.

Outcome Measure Data

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
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.
Measure Participants	176	90
Number (90% Confidence Interval) [Proportion of participants]	0.977 0.6%	0.977 1.1%

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kaplan-Meier estimate
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 90%; -0.032 to 0.032
	Parameter Dispersion	Type: Value:
	Estimation Comments	Kaplan-Meier estimate of rate difference.

3. Secondary Outcome

Title	Steady State Plasma Concentrations of Total Dabigatran at Visit 3
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

Outcome Measure Data

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
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).
Measure Participants	139
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]	79.8 (68.6)

4. Secondary Outcome

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

Outcome Measure Data

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
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).
Measure Participants	49
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]	81.7 (54.7)

5. Secondary Outcome

Title	Frequency of Dose Adjustment During the Treatment Phase
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).

Outcome Measure Data

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
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.
Measure Participants	176	90
With dose adjustment	63 35.6%	56 62.2%
With temporary interruption	25 14.1%	6 6.7%
Laboratory monitoring required	175 98.9%	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
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).

Outcome Measure Data

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
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.
Measure Participants	176	90
Count of Participants [Participants]	22 12.4%	2 2.2%

7. Secondary Outcome

Title	Freedom From Thrombus Progression at End of Therapy Compared With Baseline
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.

Outcome Measure Data

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
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.
Measure Participants	177	90
Count of Participants [Participants]	148 83.6%	73 81.1%

8. Secondary Outcome

Title	All Bleeding Events
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.

Outcome Measure Data

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
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.
Measure Participants	176	90
Any bleeding	38 21.5%	22 24.4%
Major bleeding	4 2.3%	2 2.2%
CRNM bleeding	2 1.1%	1 1.1%
Minor bleeding	33 18.6%	21 23.3%
Major and CRNM bleeding	6 3.4%	3 3.3%

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.145
	Confidence Interval	(2-Sided) 90%; 0.736 to 1.780
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	All-cause Mortality
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.

Outcome Measure Data

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
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.
Measure Participants	176	90
Number [Participants]	0 0%	1 1.1%

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
Statistical Test of Hypothesis	p-Value	0.9976
	Comments
	Method	Cox proportional hazard model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	69990000
	Confidence Interval	(2-Sided) 90%; 0.000 to 999999999
	Parameter Dispersion	Type: Value:
	Estimation Comments	Upper Limit of the 90% confidence interval was not assessable

10. Secondary Outcome

Title	All Components of the Primary Efficacy Endpoint
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.

Outcome Measure Data

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
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.
Measure Participants	177	90
Complete thrombus resolution by Day 84	81 45.8%	38 42.2%
Recurrent VTE by Day 84	7 4%	7 7.8%
VTE-related death by Day 84	0 0%	1 1.1%

11. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	119
Investigator questionnaire capsules	1.0 (0.2)
Parents questionnaire capsules	1.0 (0.0)
Patient questionnaire capsules	1.6 (0.9)

12. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	42
Investigator questionnaire pellets	1.2 (0.6)
Parents questionnaire pellets	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)
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.

Outcome Measure Data

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
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).
Measure Participants	14
Investigator questionnaire flavoured OLF	1.6 (0.8)
Investigator questionnaire unflavoured OLF	1.2 (0.4)
Parents questionnaire flavoured OLF	1.4 (0.5)
Parents questionnaire unflavoured OLF	1.8 (0.4)

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	2/176 (1.1%)		2/90 (2.2%)
Serious Adverse Events
	Dabigatran Etexilate		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/176 (14.2%)		18/90 (20%)
Blood and lymphatic system disorders
Anaemia	1/176 (0.6%)	1	0/90 (0%)	0
Febrile neutropenia	3/176 (1.7%)	3	0/90 (0%)	0
Pancytopenia	1/176 (0.6%)	1	0/90 (0%)	0
Sickle cell anaemia with crisis	0/176 (0%)	0	1/90 (1.1%)	1
Thrombocytopenia	1/176 (0.6%)	1	0/90 (0%)	0
Cardiac disorders
Cardiac arrest	0/176 (0%)	0	1/90 (1.1%)	1
Cardiac failure	0/176 (0%)	0	1/90 (1.1%)	1
Tachycardia	0/176 (0%)	0	1/90 (1.1%)	1
Eye disorders
Papilloedema	0/176 (0%)	0	1/90 (1.1%)	1
Gastrointestinal disorders
Abdominal pain	1/176 (0.6%)	1	0/90 (0%)	0
Abdominal pain upper	1/176 (0.6%)	1	0/90 (0%)	0
Gastrointestinal haemorrhage	1/176 (0.6%)	1	0/90 (0%)	0
Haematochezia	2/176 (1.1%)	3	1/90 (1.1%)	1
Haemorrhoids	1/176 (0.6%)	1	0/90 (0%)	0
Pancreatitis chronic	1/176 (0.6%)	2	0/90 (0%)	0
Peritoneal haemorrhage	0/176 (0%)	0	1/90 (1.1%)	1
Proctitis haemorrhagic	1/176 (0.6%)	2	0/90 (0%)	0
General disorders
Implant site necrosis	1/176 (0.6%)	1	0/90 (0%)	0
Infections and infestations
Erysipelas	0/176 (0%)	0	1/90 (1.1%)	1
Gastroenteritis	0/176 (0%)	0	1/90 (1.1%)	1
Gastroenteritis rotavirus	0/176 (0%)	0	1/90 (1.1%)	1
Influenza	1/176 (0.6%)	1	0/90 (0%)	0
Mastoiditis	1/176 (0.6%)	1	1/90 (1.1%)	1
Meningitis herpes	1/176 (0.6%)	1	0/90 (0%)	0
Osteomyelitis	1/176 (0.6%)	1	0/90 (0%)	0
Pneumonia viral	0/176 (0%)	0	1/90 (1.1%)	1
Sepsis	0/176 (0%)	0	1/90 (1.1%)	1
Septic shock	1/176 (0.6%)	1	0/90 (0%)	0
Staphylococcal sepsis	1/176 (0.6%)	1	0/90 (0%)	0
Wound sepsis	1/176 (0.6%)	1	0/90 (0%)	0
Injury, poisoning and procedural complications
Procedural haemorrhage	1/176 (0.6%)	1	0/90 (0%)	0
Investigations
Blood creatinine increased	1/176 (0.6%)	1	1/90 (1.1%)	1
Metabolism and nutrition disorders
Dehydration	1/176 (0.6%)	1	0/90 (0%)	0
Diabetic ketoacidosis	1/176 (0.6%)	2	0/90 (0%)	0
Hyperglycaemia	1/176 (0.6%)	1	0/90 (0%)	0
Hypoalbuminaemia	1/176 (0.6%)	1	0/90 (0%)	0
Hypoproteinaemia	1/176 (0.6%)	1	0/90 (0%)	0
Musculoskeletal and connective tissue disorders
Myositis	1/176 (0.6%)	1	0/90 (0%)	0
Pain in extremity	1/176 (0.6%)	1	1/90 (1.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/176 (0.6%)	1	0/90 (0%)	0
Nervous system disorders
Haemorrhage intracranial	1/176 (0.6%)	1	0/90 (0%)	0
Hepatic encephalopathy	1/176 (0.6%)	1	0/90 (0%)	0
Tension headache	0/176 (0%)	0	1/90 (1.1%)	2
Psychiatric disorders
Suicidal ideation	0/176 (0%)	0	1/90 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/176 (0.6%)	1	0/90 (0%)	0
Asthmatic crisis	0/176 (0%)	0	1/90 (1.1%)	1
Dyspnoea	0/176 (0%)	0	1/90 (1.1%)	1
Pulmonary embolism	0/176 (0%)	0	2/90 (2.2%)	2
Respiratory failure	1/176 (0.6%)	1	0/90 (0%)	0
Tachypnoea	0/176 (0%)	0	1/90 (1.1%)	1
Vascular disorders
Deep vein thrombosis	2/176 (1.1%)	2	3/90 (3.3%)	3
Embolism venous	0/176 (0%)	0	1/90 (1.1%)	1
Haemorrhagic infarction	0/176 (0%)	0	1/90 (1.1%)	1
Post thrombotic syndrome	1/176 (0.6%)	1	0/90 (0%)	0
Shock	0/176 (0%)	0	1/90 (1.1%)	1
Takayasu's arteritis	1/176 (0.6%)	1	0/90 (0%)	0
Thrombophlebitis superficial	1/176 (0.6%)	1	0/90 (0%)	0
Thrombosis	0/176 (0%)	0	1/90 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Dabigatran Etexilate		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/176 (33.5%)		16/90 (17.8%)
Gastrointestinal disorders
Diarrhoea	9/176 (5.1%)	11	1/90 (1.1%)	1
Dyspepsia	10/176 (5.7%)	10	0/90 (0%)	0
Vomiting	14/176 (8%)	18	1/90 (1.1%)	1
General disorders
Pyrexia	11/176 (6.3%)	12	3/90 (3.3%)	3
Infections and infestations
Nasopharyngitis	11/176 (6.3%)	12	7/90 (7.8%)	7
Nervous system disorders
Headache	17/176 (9.7%)	26	4/90 (4.4%)	4
Respiratory, thoracic and mediastinal disorders
Epistaxis	8/176 (4.5%)	9	6/90 (6.7%)	13

Limitations/Caveats

[Not Specified]

More Information

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.