Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial - 07/09/13

Doi : 10.1016/j.ahj.2013.04.009

Stephen E. Kimmel, MD, MSCE ^a,^{^⁎,}^{^{j
for the COAG Investigators.}} , Benjamin French, PhD ^a,^{^{j
for the COAG Investigators.}}, Jeffrey L. Anderson, MD ^b,^{^{j
for the COAG Investigators.}}, Brian F. Gage, MD, MSc ^c,^{^{j
for the COAG Investigators.}}, Julie A. Johnson, PharmD ^d,^{^{j
for the COAG Investigators.}}, Yves D. Rosenberg, MD, MPH ^e,^{^{j
for the COAG Investigators.}}, Nancy L. Geller, PhD ^e,^{^{j
for the COAG Investigators.}}, Scott E. Kasner, MD, FAHA ^a,^{^{j
for the COAG Investigators.}}, Charles S. Eby, MD ^c,^{^{j
for the COAG Investigators.}}, Jungnam Joo, PhD ^e,^{^{j
for the COAG Investigators.}}, Michael D. Caldwell, MD, PhD ^f,^{^{j
for the COAG Investigators.}}, Samuel Z. Goldhaber, MD ^g,^{^{j
for the COAG Investigators.}}, Robert G. Hart, MD ^h,^{^{j
for the COAG Investigators.}}, Denise Cifelli, MS ^a,^{^{j
for the COAG Investigators.}}, Rosemary Madigan, RN, MPH ^a,^{^{j
for the COAG Investigators.}}, Colleen M. Brensinger, MS ^a,^{^{j
for the COAG Investigators.}}, Suzanne Goldberg, RN, MSN ^e,^{^{j
for the COAG Investigators.}}, Robert M. Califf, MD ^i,^{^{j
for the COAG Investigators.}}, Jonas H. Ellenberg, PhD ^a,^{^{j
for the COAG Investigators.}}
^a Perelman School of Medicine, University of Pennsylvania Health System, Philadelphia, PA
^b University of Utah, School of Medicine, Salt Lake City, UT
^c Washington University School of Medicine in St Louis, St Louis, MO
^d University of Florida, Gainesville, FL
^e National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda, MD
^f Marshfield Clinic, Marshfield, WI
^g Brigham and Women's Hospital, Harvard Medical School, Boston, MA
^h University of Texas Health Science Center, San Antonio, TX
ⁱ Duke University Medical Center, Durham, NC

^⁎Reprint requests: Stephen E. Kimmel, MD, MSCE, University of Pennsylvania School of Medicine, 923 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.

Résumé

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.

Conclusion

The COAG will determine if genetic information provides added benefit above and beyond clinical information alone.

Le texte complet de cet article est disponible en PDF.

Plan

Scientific and statistical methods

Objectives and design of the COAG study

Study population

Randomization

Study outcomes

Initial and dose adjustment phase (days 1-5) using algorithms

Administration of dosing

Administration of study drug

Genotyping at the central laboratory

Study visits

Statistical considerations

Data and safety monitoring

Sample size adjustments

Discussion

	W.H. Wilson Tang, MD served as guest editor for this article.
	This work was supported under contract HHSN268200800003C from the National Heart Lung and Blood Institute.
	RCT number NCT00839657.

Export

Vol 166 - N° 3

P. 435 - septembre 2013 Retour au numéro

Article précédent

Evaluation of the dual peroxisome proliferator–activated receptor ?/? agonist aleglitazar to reduce cardiovascular events in patients with acute coronary syndrome and type 2 diabetes mellitus: Rationale and design of the AleCardio trial
A. Michael Lincoff, Jean-Claude Tardif, Bruce Neal, Stephen J. Nicholls, Lars Rydén, Gregory G. Schwartz, Klas Malmberg, John B. Buse, Robert R. Henry, Hans Wedel, Arlette Weichert, Ruth Cannata, Diederick E. Grobbee

| Article suivant

Improving outcomes in patients with atrial fibrillation: Rationale and design of the Early treatment of Atrial fibrillation for Stroke prevention Trial
Paulus Kirchhof, Günter Breithardt, A. John Camm, Harry J. Crijns, Karl-Heinz Kuck, Panos Vardas, Karl Wegscheider

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial - 07/09/13

Résumé

Background

Methods

Results

Conclusion

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL