title: Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design.
abstract: The risk of venous thromboembolism (VTE) is higher after the total hip or knee replacement surgery than after almost any other surgical procedure; warfarin sodium is commonly prescribed to reduce this peri-operative risk. Warfarin has a narrow therapeutic window with high inter-individual dose variability and can cause hemorrhage. The genetics-informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT) is a 2 × 2 factorial-design, randomized controlled trial designed to compare the safety and effectiveness of warfarin-dosing strategies. GIFT will answer two questions: (1) does pharmacogenetic (PGx) dosing reduce the rate of adverse events in orthopedic patients; and (2) is a lower target international normalized ratio (INR) non-inferior to a higher target INR in orthopedic participants? The composite primary endpoint of the trial is symptomatic and asymptomatic VTE (identified on screening ultrasonography), major hemorrhage, INR ≥ 4, and death.
authors: Department of Internal Medicine, Washington University, St Louis, MO, USA.
authors: E J
authors: EJ
authors: Do
authors: P
authors: P
authors: Lenzini
authors: C S
authors: CS
authors: Eby
authors: A R
authors: AR
authors: Bass
authors: G A
authors: GA
authors: McMillin
authors: S M
authors: SM
authors: Stevens
authors: S C
authors: SC
authors: Woller
authors: R C
authors: RC
authors: Pendleton
authors: J L
authors: JL
authors: Anderson
authors: P
authors: P
authors: Proctor
authors: R M
authors: RM
authors: Nunley
authors: V
authors: V
authors: Davila-Roman
authors: B F
authors: BF
authors: Gage
references: Ann Intern Med. 2002 Oct 15;137(8):648-55
references: 12379064
references: Clin Trials. 2010 Oct;7(5):597-604
references: 20693186
references: Blood. 2007 Sep 1;110(5):1511-5
references: 17387222
references: Pharmacogenomics J. 2005;5(4):262-70
references: 15883587
references: Am J Med. 1993 Sep;95(3):315-28
references: 8368229
references: Chest. 2001 Jan;119(1 Suppl):22S-38S
references: 11157641
references: Thromb Haemost. 2005 Apr;93(4):700-5
references: 15841315
references: Clin Pharmacol Ther. 2008 Feb;83(2):312-21
references: 17653141
references: Arch Intern Med. 2000 Dec 11-25;160(22):3431-6
references: 11112236
references: J Arthroplasty. 2010 Jan;25(1):121-7
references: 19062248
references: Ther Drug Monit. 2010 Jun;32(3):338-45
references: 20386359
references: J Thromb Haemost. 2004 Aug;2(8):1327-33
references: 15304038
references: N Engl J Med. 2003 Oct 30;349(18):1703-12
references: 14585938
references: Thromb Haemost. 2004 Jan;91(1):87-94
references: 14691573
references: J Thromb Thrombolysis. 2002 Dec;14(3):227-32
references: 12913403
references: Thromb Haemost. 2000 Nov;84(5):775-8
references: 11127854
references: Ann Intern Med. 2003 Dec 2;139(11):893-900
references: 14644891
references: J Cardiovasc Pharmacol Ther. 1999 Jan;4(1):3-8
references: 10684518
references: Pharmacogenet Genomics. 2009 Mar;19(3):226-34
references: 19177029
references: Clin Chem. 2009 Oct;55(10):1861-8
references: 19679631
references: Circulation. 2007 May 29;115(21):2689-96
references: 17515465
references: Am J Med. 1999 Nov;107(5):414-24
references: 10569295
references: Circulation. 2007 Nov 27;116(22):2563-70
references: 17989110
references: N Engl J Med. 2003 Apr 10;348(15):1425-34
references: 12601075
references: J Am Coll Cardiol. 2010 Jun 22;55(25):2804-12
references: 20381283
references: Circulation. 2003 Apr 1;107(12):1692-711
references: 12668507
references: Blood. 2005 Jan 15;105(2):645-9
references: 15358623
references: Ann Intern Med. 1993 Apr 1;118(7):511-20
references: 8280198
references: Ann Intern Med. 2009 Jan 20;150(2):73-83
references: 19153410
references: JAMA. 2002 Apr 3;287(13):1690-8
references: 11926893
references: Clin Pharmacol Ther. 2007 May;81(5):742-7
references: 17329985
references: AJR Am J Roentgenol. 1996 Mar;166(3):659-62
references: 8623645
references: Ann Pharmacother. 2007 Nov;41(11):1798-804
references: 17911206
references: J Thromb Haemost. 2008 Sep;6(9):1445-9
references: 18627440
references: N Engl J Med. 2003 Aug 14;349(7):631-9
references: 12917299
references: Pharmacogenomics. 2009 Oct;10(10):1687-95
references: 19842940
references: N Engl J Med. 2005 Jun 2;352(22):2285-93
references: 15930419
references: J Thromb Haemost. 2008 Oct;6(10):1655-62
references: 18662264
references: Ann Pharmacother. 2005 Jun;39(6):1002-7
references: 15886295
references: Thromb Haemost. 1993 Mar 1;69(3):236-9
references: 8470047
references: Clin Med Res. 2005 Aug;3(3):137-45
references: 16160068
references: Thromb Haemost. 2010 Oct;104(4):750-4
references: 20694283
references: Clin Pharmacol Ther. 2008 Mar;83(3):460-70
references: 17851566
references: Hum Mol Genet. 2005 Jul 1;14(13):1745-51
references: 15888487
references: Clin Pharmacol Ther. 2008 Sep;84(3):326-31
references: 18305455
references: Chest. 2008 Jun;133(6 Suppl):381S-453S
references: 18574271
references: Blood. 2008 Apr 15;111(8):4106-12
references: 18250228
references: Blood Cells Mol Dis. 2009 Jul-Aug;43(1):119-28
references: 19297219
references: Pharmacotherapy. 2008 Feb;28(2):141-3
references: 18225960