Apixaban Discontinuation Prior to Major Surgery (ADIOS)

The ADIOS study is a prospective, observational study will evaluate one hundred and thirty (130) patients with non-valvular atrial fibrillation who are currently receiving treatment with apixaban as indicated to reduce the risk of stroke or systemic embolism, and who require an elective major surgical or invasive procedure will be included in the study. The purpose of the study is to evaluate the efficacy of the recommended pre-procedure washout period of 48 hours.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Thromboembolism
• Intervention / Treatment: Other: Lab tests for plasma levels of apixaban and anti-10a factor

Detailed Description

This study will estimate for what proportion of patients a 48 hour pre-procedure apixaban discontinuation is sufficient to achieve minimal apixaban plasma levels (less than 30 ng/mL) prior to surgery. The investigators hypothesize that this portion will be 80-95%.

All patients will have a blood draw at 48 hours prior to procedure and then a second blood draw on the morning of the procedure to test apixaban plasma and anti-Xa levels. Patients will also receive a follow-up phone call at 30 days to collect information on clinical events.

• Study Type: Observational
• Enrollment (Anticipated): 130

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

130 patients who are currently receiving treatment with apixaban for non-valvular atrial fibrillation and scheduled for an elective surgical procedure.

Description

Inclusion Criteria:

• At least 18 years of age
• On long term anticoagulation with apixaban for treatment of non-valvular atrial fibrillation or venous thromboembolism
• Undergoing elective major surgery or invasive procedure

Exclusion Criteria:

• Inability to obtain informed consent for the blood sample draws
• Any condition precluding collection of follow-up information
• Participation in another clinical trial
• Apixaban Package Insert Recommendations and Cautions
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
• Women must not be breastfeeding
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of study drug apixaban (approximately 3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post- treatment completion.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of the study drug (approximately 3 days) plus 90 days (duration of sperm turnover) for a total of 93 days post-treatment completion.
• Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However WOCBP must still undergo pregnancy testing as described.
• The safety and efficacy of apixaban have not been studied in patients with prosthetic heart valves. Therefore, use is not recommended in these patients.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apixaban plasma concentration	Determine whether the recommended 48 hour pre-procedure discontinuation period is sufficient to achieve minimal apixaban plasma concentration of < 30 ng/ml prior to surgery	Prior to elective surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-10a apixaban plasma concentration	Assess changes in anti-Xa apixaban levels following apixaban discontinuation but prior to the procedure	Prior to elective surgery
30 day outcomes assessment	Incidence of major events within 30 days including bleeding events, arterial thromboembolic events, and deaths caused by bleeding or thrombosis.	Up to 30 days post- procedure

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Geno J. Merli, MD, Thomas Jefferson University

Publications and helpful links

General Publications

• Merli GJ, Kraft WK, Eraso LH, Galanis T, Thomson LJ, Ouma GO, Viscusi E, Gong JZ, Lam E. Apixaban Discontinuation for Invasive Or major Surgical procedures (ADIOS): A prospective cohort study. Vasc Med. 2022 Jun;27(3):269-276. doi: 10.1177/1358863X211047270. Epub 2021 Nov 22.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: October 14, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (Estimate): October 17, 2016

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 11, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Hemorrhage; Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: 16G.421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO