Open Label Study Comparing Efficacy and Safety of Dabigatran Etexilate to Standard of Care in Paediatric Patients With Venous Thromboembolism (VTE)
- Conditions
- Venous Thromboembolism
- Interventions
- Drug: standard of careDrug: dabigatran etexilate
- Registration Number
- NCT01895777
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 267
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description standard of care 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) dabigatran etexilate dabigatran etexilate Dabigatran etexilate capsules, pellets or liquid formulation given BID in an open label fashion for 3 months
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
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
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
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.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.
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.
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.
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.
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.
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.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.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.
Trial Locations
- Locations (65)
Hospital General de Niños Pedro de Elizalde
🇦🇷Caba, Argentina
UZ Leuven
🇧🇪Leuven, Belgium
AKH - Medical University of Vienna
🇦🇹Wien, Austria
Brussels - UNIV Saint-Luc
🇧🇪Bruxelles, Belgium
UNIV UZ Gent
🇧🇪Gent, Belgium
Faculdade de Ciencias Medicas da UNICAMP
🇧🇷Campinas, Brazil
PenSI - Pesquisa e Ensino em Saude Infantil
🇧🇷Sao Paulo, Brazil
Instituto de Crianca / Hospital das Clínicas-FMUSP
🇧🇷Sao Paulo, Brazil
CHU Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Medical University of Innsbruck
🇦🇹Innsbruck, Austria
HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
🇧🇷Campinas, Brazil
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Reg.Children Hosp.Dnipropetrovsk
🇺🇦Dnipropetrovsk, Ukraine
Reg.Children Hosp,Vinnytsia
🇺🇦Vinnytsya, Ukraine
Hospital Infantil Universitario Niño Jesus
🇪🇸Madrid, Spain
Oslo Universitetssykehus HF, Rikshospitalet
🇳🇴Oslo, Norway
Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo
🇷🇺Kemerovo, Russian Federation
Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery
🇷🇺Tyument, Russian Federation
Izmilovskaya Child City ClinHosp,Haematological Dept, Moscow
🇷🇺Moscow, Russian Federation
University Debrecen Hospital
🇭🇺Debrecen, Hungary
Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan
🇷🇺Kazan, Russian Federation
Hacettepe Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Akdeniz Universitesi Tip Fakultesi
🇹🇷Antalya, Turkey
Sahlgrenska US, Göteborg
🇸🇪Göteborg, Sweden
Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol
🇷🇺Moscow, Russian Federation
St.Petersburg State Pediatric Univ.Ministry of Healthcare RF
🇷🇺St. Petersburg, Russian Federation
Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg
🇷🇺Yekaterinburg, Russian Federation
Necmettin Erbakan Universitesi Meram Tip Fakultesi
🇹🇷Konya, Turkey
Karolinska Univ. sjukhuset
🇸🇪Solna, Sweden
Ospedale Infantile Regina Margherita
🇮🇹Torino, Italy
Universitäts-Kinderspital
🇨🇭Zürich, Switzerland
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali
🇹🇷Izmir, Turkey
TaUH, Pediatric Early Phase Trial Unit
🇫🇮Tampere, Finland
Shaare Zedek Medical Center, Jerusalem 91031
🇮🇱Jerusalem, Israel
Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius
🇱🇹Vilnius, Lithuania
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Nuevo León, Mexico
Haukeland Universitetssykehus
🇳🇴Bergen, Norway
University Hospital Ostrava
🇨🇿Ostrava, Czechia
Università degli Studi "La Sapienza"
🇮🇹Roma, Italy
University Hospital Plzen, Plzen-Lochotin
🇨🇿Plzen-Lochotin, Czechia
HOP de la Cavale Blanche
🇫🇷Brest cedex, France
"Aghia Sophia" Children's Hospital
🇬🇷Athens, Greece
Instituto Nacional de Pediatría
🇲🇽México D.F, Mexico
Universitätsklinikum Essen AöR
🇩🇪Essen, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Cukurova Universitesi Tip Fakultesi Cocuk Sagligi
🇹🇷Adana, Turkey
Istanbul Universitesi Cerrahpasa Tip Fakultesi
🇹🇷Istanbul, Turkey
Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH
🇹🇷Istanbul, Turkey
St. Joseph's Children's Hospital
🇺🇸Tampa, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
General Univ.hosp Hradec Kralove
🇨🇿Hradec Kralove, Czechia
University Hospital Brno
🇨🇿Brno, Czechia
University Hospital Olomouc
🇨🇿Olomouc, Czechia
University Hospital Motol
🇨🇿Prague, Czechia
Rigshospitalet, København, Børneonkologisk Afsnit 5002
🇩🇰Copenhagen, Denmark
University of California Davis
🇺🇸Sacramento, California, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States