Safety of Dabigatran Etexilate in Blood Clot Prevention in Children

Venous Thromboembolism Clinical Trial

Official title:

Open Label, Single Arm Safety Prospective Cohort Study of Dabigatran Etexilate for Secondary Prevention of Venous Thromboembolism in Children From 0 to Less Than 18 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02197416
• Other study ID #: 1160.108
• Secondary ID: 2014-000583-18
• Status: Completed
• Phase: Phase 3
• Start date: September 29, 2014
• Est. completion date: November 19, 2019

Study information

• Verified date: May 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label, single arm prospective cohort study will assess the safety of dabigatran etexilate in secondary prevention of venous thromboembolism in paediatric patients. Children from 0 to less than 18 years of age will be eligible to participate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: November 19, 2019
• Est. primary completion date: October 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion criteria:

• Male or female subjects 0 to less than 18 years of age at the time of informed consent / assent

• Previously documented objective diagnosis of VTE, followed by completed course of initial VTE treatment for at least 3 months (in case of VKA - intended INR between 2 and 3) or completed study treatment (i.e. reached Visit 8) in the 1160.106 trial. Patients, who during the treatment phase of 1160.106 trial were switched from dabigatran etexilate to SOC arm for any reason, are not eligible for this study.

• Presence of an unresolved clinical risk factor requiring further anticoagulation for secondary VTE prevention (e.g. central venous line, underlying disease, thrombophilia, etc.)

• Written informed consent form (ICF) provided by the patient's parent or legal guardian and assent provided by the patient (if applicable) at the time of ICF signature according to local regulations.

• Further inclusion criteria apply

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 an acceptable method of birth control, or do not plan to continue using this method throughout the study and / or do not agree to adhere to pregnancy testing required by this protocol

• Patients in age group 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 restricted medication prior to first dose of study medication

• Patients who have received an investigational drug in the past 30 days prior to screening, except patients who have completed the treatment period (up to Visit 8) in 1160.106 trial

• 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

• Further exclusion criteria apply

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Secondary Prevention
• Thromboembolism
• Venous Thromboembolism

Intervention

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

Locations

Country	Name	City	State
Austria	AKH - Medical University of Vienna	Wien
Belgium	Brussels - UNIV UZ Brussel	Brussel
Belgium	UNIV UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Brazil	Faculdade de Ciencias Medicas da UNICAMP	Campinas
Brazil	HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas	Campinas
Brazil	Instituto de Oncologia Pediatrica - IOP / GRAAC - UNIFESP	Sao Paulo
Canada	Kingston General Hospital	Kingston	Ontario
Canada	CHU Sainte-Justine	Montreal	Ontario
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Ostrava	Ostrava
Czechia	University Hospital Plzen, Plzen-Lochotin	Plzen - Lochotin
Czechia	University Hospital Motol	Prague
Denmark	Rigshospitalet, København, Børneonkologisk Afsnit 5002	Copenhagen
France	HOP Timone	Marseille
Germany	Universitätsklinikum Essen AöR	Essen
Germany	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen
Germany	Universitätsklinikum Münster	Münster
Hungary	University Debrecen Hospital	Debrecen
Israel	Shaare Zedek Medical Center, Jerusalem 91031	Jerusalem
Italy	A.O. Univ. Policlinico "Paolo Giaccone"	Palermo
Italy	Osp. Pediatrico Bambin Gesù	Roma
Italy	Università degli Studi "La Sapienza"	Roma
Italy	Ospedale Infantile Regina Margherita	Torino
Lithuania	Children Intensive Care Hosp,Anaesthesiology Dept,Vilnius	Vilnius
Mexico	Instituto Nacional de Pediatría	Mexico DF
Norway	Haukeland Universitetssykehus	Bergen
Norway	Oslo Universitetssykehus HF, Rikshospitalet	Oslo
Russian Federation	Children Rep.Clin.Hosp of MoH,Cardio Vas.surgery Dept, Kazan	Kazan
Russian Federation	Science Res.Instit.CV Diseases,Scientific Res.Dept,Kemerovo	Kemerovo
Russian Federation	Child.CityClin.Hos.na.ZA Bashlyaeva MoscowHealth Dep,Cardiol	Moscow
Russian Federation	Morozovskaya Children Clin.Hosp.,Haematological Dept, Moscow	Moscow
Russian Federation	St.Petersburg State Pediatric Univ.Ministry of Healthcare RF	St. Petersburg
Russian Federation	Reg Clin.Hosp.#1,Healthcare Tyumen Region,Cardiovas.Surgery	Tyument
Russian Federation	State Budget Healthcare Institution "Republican children's clinical hospital"	Ufa
Russian Federation	Childr.CityClin.Hos#9,pediatric&Neonatal Neurol.Ekaterinburg	Yekaterinburg
Sweden	Karolinska Univ. sjukhuset	Solna
Switzerland	Universitäts-Kinderspital	Zürich
Taiwan	Taichung Veterans General Hospital	Taichung
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Turkey	Cukurova Universitesi Tip Fakultesi Cocuk Sagligi	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Akdeniz Universitesi Tip Fakultesi	Antalya
Turkey	Istanbul Saglik Bilimleri Uni. Kanuni Sultan Suleyman EAH	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Cocuk Hematolojisi Bilim Dali	Izmir
Turkey	Necmettin Erbakan Universitesi Meram Tip Fakultesi	Konya
Ukraine	Reg.Children Hosp.Dnipropetrovsk	Dnipropetrovsk
Ukraine	Western Ukrainian Spec.Children Med.Center,Lviv	Lviv
Ukraine	Reg.Children Hosp,Vinnytsia	Vinnytsya
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Alliance for Childhood Diseases	Las Vegas	Nevada
United States	University of Miami	Miami	Florida
United States	University of California Davis	Sacramento	California
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	St. Joseph's Children's Hospital	Tampa	Florida
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Lithuania,  Mexico,  Norway,  Russian Federation,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Probability of Recurrence of Venous Thromboembolism (VTE) at 6 and 12 Months	The event-free probability of first recurrence of VTE were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months.; Patients who did not experience recurrent VTE at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-VTE related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and 12 (Week 52) of on treatment period
Primary	Event-free Probability of Major or Minor (Including Clinically Relevant Non-major (CRNM)) Bleeding Events at 6 and 12 Months	The event-free probability of major or minor (including CRNM) bleeding event were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months.; Patients who did not experience major or minor (including CRNM) bleeding event at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-bleeding related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and month 12 (Week 52) of on treatment period
Primary	Event-free Probability of Mortality Overall and Related to Thrombotic or Thromboembolic Events at 6 and 12 Months	The event-free probability of mortality overall and related to thrombotic or thromboembolic events were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months.; Patients who did not experience mortality overall and related to thrombotic or thromboembolic events at the time of analysis, dropped out from the trial early, were lost to follow-up, were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and 12 (Week 52) of on treatment period
Secondary	Event-free Probability of Occurrence of Post-thrombotic Syndrome (PTS) at 6 and 12 Months	The event-free probability of PTS were provided by Kaplan-Meier estimation with its 95% confidence intervals (CIs) at 6 and 12 months. Patients who did not experience PTS at the time of analysis, dropped out from the trial early, were lost to follow-up, or had died from non-PTS related cause were considered as non-events and censored. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	At month 6 (Week 26) and 12 (Week 52) of on treatment period
Secondary	Percentage of Participants With Dabigatran Etexilate (DE) Dose Adjustments During on Treatment Period	Percentage of participants with dabigatran etexilate dose adjustments during on treatment period. On treatment period was from first DE administration to 3 days of residual effect period after last DE administration.	From first DE administration to 3 days of residual effect period after last DE administration, up to 52 weeks+ 3 days
Secondary	Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)		At Visit 3 (day 4 after first dose of trial medication)
Secondary	Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)		Pharmacodynamics (PD) samples were collected from first dose of trial medication at day 1 and day 4, 22, 43, 85, 127, 183, 239 and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.
Secondary	Central Measurement of Ecarin Clotting Time (ECT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)		At Visit 3 (day 4 after first dose of trial medication)
Secondary	Central Measurement of Ecarin Clotting Time (ECT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)		Pharmacodynamics (PD) samples were collected from first dose of trial medication at day 1 and day 4, 22, 43, 85, 127, 183, 239 and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.
Secondary	Central Measurement of Diluted Thrombin Time (dTT) at Visit 3 (After at Least Six Consecutive Dabigatran Etexilate (DE) Doses)		At Visit 3 (day 4 after first dose of trial medication)
Secondary	Central Measurement of Diluted Thrombin Time (dTT) at Post-titration (After at Least 3 Days Following Any Dabigatran Etexilate (DE) Dose Adjustment)		dTT values were collected at day 4, 22, 43, 85, 127, 183, 239, and 295 until last dose at day 365 and at post-titration (at least 3 days after dose adjustment) if needed, up to 365 days.

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