title: Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial.
abstract: BACKGROUND
  Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin.
  
  
  METHODS
  The COAG trial is a multicenter, double-blind, randomized trial comparing 2 approaches to guiding warfarin therapy initiation: initiation of warfarin therapy based on algorithms using clinical information plus an individual's genotype using genes known to influence warfarin response ("genotype-guided dosing") versus only clinical information ("clinical-guided dosing") (www.clinicaltrials.gov Identifier: NCT00839657).
  
  
  RESULTS
  The COAG trial design is described. The study hypothesis is that, among 1,022 enrolled patients, genotype-guided dosing relative to clinical-guided dosing during the initial dosing period will increase the percentage of time that patients spend in the therapeutic international normalized ratio range in the first 4 weeks of therapy.
  
  
  CONCLUSIONS
  The COAG will determine if genetic information provides added benefit above and beyond clinical information alone.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania Health System, Philadelphia, PA. Electronic address: stevek@mail.med.upenn.edu.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Brian F
authors.initials: BF
authors.lastname: Gage
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Yves D
authors.initials: YD
authors.lastname: Rosenberg
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Geller
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.forename: Charles S
authors.initials: CS
authors.lastname: Eby
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.forename: Michael D
authors.initials: MD
authors.lastname: Caldwell
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
authors.forename: Denise
authors.initials: D
authors.lastname: Cifelli
authors.forename: Rosemary
authors.initials: R
authors.lastname: Madigan
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Brensinger
authors.forename: Suzanne
authors.initials: S
authors.lastname: Goldberg
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Jonas H
authors.initials: JH
authors.lastname: Ellenberg
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D019934:International Normalized Ratio; D013923:Thromboembolism / Q000209:etiology*; D016896:Treatment Outcome; D014481:United States; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
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