Thromb Haemost 2017; 117(12): 2415-2424
DOI: 10.1160/TH17-08-0553
Trial Protocol Design Paper
Schattauer GmbH Stuttgart

The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale

James D. Douketis
,
Alex C. Spyropoulos
,
Julia M. Anderson
,
Donald M. Arnold
,
Shannon M. Bates
,
Mark Blostein
,
Marc Carrier
,
Joseph A. Caprini
,
Nathan P. Clark
,
Michiel Coppens
,
Francesco Dentali
,
Joanne Duncan
,
Peter L. Gross
,
Jeannine Kassis
,
Stephen Kowalski
,
Agnes Y. Lee
,
Gregoire Le Gal
,
Geneviève Le Templier
,
Na Li
,
Elizabeth MacKay
,
Vinay Shah
,
Sudeep Shivakumar
,
Susan Solymoss
,
Frederick A. Spencer
,
Summer Syed
,
Alfonso J. Tafur
,
Thomas Vanassche
,
Thomas Thiele
,
Cynthia Wu
,
Erik Yeo
,
Sam Schulman
Further Information

Publication History

11 August 2017

12 September 2017

Publication Date:
06 December 2017 (online)

Abstract

Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol.

Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group.

Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.

Funding

The PAUSE study is funded by grants from the Canadian Institutes of Health Research (grant no. 313156) and the Heart and Stroke Foundation of Canada (grant no. G-14–0006163), and by in-kind support from Aniara—Hyphen Biomed, which provided the DOAC-specific coagulation assays for residual anticoagulation measurements.


 
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