PMID- 30046738
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230926
IS  - 2475-0379 (Electronic)
IS  - 2475-0379 (Linking)
VI  - 2
IP  - 2
DP  - 2018 Apr
TI  - Design and rationale for the DIVERSITY study: An open-label, randomized study of 
      dabigatran etexilate for pediatric venous thromboembolism.
PG  - 347-356
LID - 10.1002/rth2.12086 [doi]
AB  - BACKGROUND: The current standard of care (SOC) for pediatric venous 
      thromboembolism (VTE) comprises unfractionated heparin (UFH), or 
      low-molecular-weight heparin (LMWH) followed by LMWH or vitamin K antagonists, 
      all of which have limitations. Dabigatran etexilate (DE) has demonstrated 
      efficacy and safety for adult VTE and has the potential to overcome some of the 
      limitations of the current SOC. Pediatric trials are needed to establish dosing 
      in children and to confirm that results obtained in adults are applicable in the 
      pediatric setting. OBJECTIVES: To describe the design and rationale of a planned 
      phase IIb/III trial that will evaluate a proposed dosing algorithm for DE and 
      assess the safety and efficacy of DE versus SOC for pediatric VTE treatment. 
      PATIENTS/METHODS: An open-label, randomized, parallel-group noninferiority study 
      will be conducted in approximately 180 patients aged 0 to <18 years with VTE, who 
      have received initial UFH or LMWH treatment and who are expected to require 
      >/=3 months of anticoagulation therapy. Patients will receive DE or SOC for 
      3 months. DE will be administered twice daily as capsules, pellets, or an oral 
      liquid formulation according to patient age. Initial doses will be calculated 
      using a proposed dosing algorithm. RESULTS: There will be two coprimary 
      endpoints: a composite efficacy endpoint comprising the proportion of patients 
      with complete thrombus resolution, freedom from recurrent VTE and VTE-related 
      mortality, and a safety endpoint: freedom from major bleeding events. CONCLUSION: 
      Findings will provide valuable information regarding the efficacy and safety of 
      DE for the treatment of pediatric VTE. ClinicalTrials.gov registration number: 
      NCT01895777.
FAU - Albisetti, Manuela
AU  - Albisetti M
AD  - Hematology Department University Children's Hospital Zurich Switzerland.
FAU - Biss, Branislav
AU  - Biss B
AD  - Department of Clinical Development Boehringer Ingelheim RCV GmbH & Co. KG Vienna 
      Austria.
FAU - Bomgaars, Lisa
AU  - Bomgaars L
AD  - Department for Pediatrics Baylor College of Medicine Houston TX USA.
FAU - Brandao, Leonardo R
AU  - Brandao LR
AD  - Department of Pediatrics Division of Hematology/Oncology University of Toronto 
      The Hospital for Sick Children Toronto ON Canada.
FAU - Brueckmann, Martina
AU  - Brueckmann M
AD  - Clinical Development and Medical Affairs Boehringer Ingelheim Pharma GmbH& Co. KG 
      Ingelheim Germany.
AD  - Faculty of Medicine Mannheim University of Heidelberg Mannheim Germany.
FAU - Chalmers, Elizabeth
AU  - Chalmers E
AD  - Royal Hospital for Children Glasgow Scotland.
FAU - Gropper, Savion
AU  - Gropper S
AD  - Clinical Development and Medical Affairs Boehringer Ingelheim Pharma GmbH& Co. KG 
      Ingelheim Germany.
FAU - Harper, Ruth
AU  - Harper R
AD  - Boehringer Ingelheim Ltd Bracknell Berkshire UK.
FAU - Huang, Fenglei
AU  - Huang F
AD  - Translational Medicine and Clinical Pharmacology Boehringer Ingelheim 
      Pharmaceuticals, Inc. Ridgefield CT USA.
FAU - Luciani, Matteo
AU  - Luciani M
AD  - OncoHematology Department Bambino Gesu Children's Hospital Rome Italy.
FAU - Manastirski, Ivan
AU  - Manastirski I
AD  - Department of Clinical Development Boehringer Ingelheim RCV GmbH & Co. KG Vienna 
      Austria.
FAU - Mitchell, Lesley G
AU  - Mitchell LG
AD  - University of Alberta Edmonton AB Canada.
FAU - Tartakovsky, Igor
AU  - Tartakovsky I
AD  - Clinical Development and Medical Affairs Boehringer Ingelheim Pharma GmbH& Co. KG 
      Ingelheim Germany.
FAU - Wang, Bushi
AU  - Wang B
AD  - Biostatistics and Data Sciences Boehringer Ingelheim Pharmaceuticals, Inc. 
      Ridgefield CT USA.
FAU - Halton, Jacqueline M L
AU  - Halton JML
AD  - Children's Hospital of Eastern Ontario University of Ottawa Ottawa ON Canada.
LA  - eng
SI  - ClinicalTrials.gov/NCT01895777
PT  - Journal Article
DEP - 20180325
PL  - United States
TA  - Res Pract Thromb Haemost
JT  - Research and practice in thrombosis and haemostasis
JID - 101703775
PMC - PMC6055566
OTO - NOTNLM
OT  - anticoagulants
OT  - dabigatran etexilate
OT  - direct thrombin inhibitors
OT  - pediatrics
OT  - venous thromboembolism
EDAT- 2018/07/27 06:00
MHDA- 2018/07/27 06:01
PMCR- 2018/03/25
CRDT- 2018/07/27 06:00
PHST- 2017/06/29 00:00 [received]
PHST- 2018/01/26 00:00 [accepted]
PHST- 2018/07/27 06:00 [entrez]
PHST- 2018/07/27 06:00 [pubmed]
PHST- 2018/07/27 06:01 [medline]
PHST- 2018/03/25 00:00 [pmc-release]
AID - S2475-0379(22)01721-6 [pii]
AID - RTH212086 [pii]
AID - 10.1002/rth2.12086 [doi]
PST - epublish
SO  - Res Pract Thromb Haemost. 2018 Mar 25;2(2):347-356. doi: 10.1002/rth2.12086. 
      eCollection 2018 Apr.