Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis

Atrial Fibrillation Clinical Trial

— SAFE-D  

Official title:

Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis (SAFE-D)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03987711
• Other study ID #: SAFE-D-01
• Status: Completed
• Phase: Phase 2
• Start date: December 10, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2023
• Source: Unity Health Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prevention of atrial fibrillation related thromboembolism in the dialysis population is unclear. While the practice of anticoagulation appears favorable in patients with mild-to-moderate chronic kidney disease, no patients with severe chronic kidney disease (estimated glomerular filtration rate <25 ml/min), and specifically those receiving dialysis, have been included in randomized trials.Moreover, the effect of anticoagulation in the dialysis population may fundamentally differ from those studied in clinical trials. Accordingly, characterization of the optimal management strategy to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation receiving dialysis is a priority. The overall goal of this pilot trial is to evaluate the feasibility of conducting a randomized controlled trial comparing anticoagulation strategies in patients with atrial fibrillation receiving dialysis (either hemodialysis or peritoneal dialysis).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years.

2. Receiving maintenance hemodialysis or peritoneal dialysis for > 90 days.

3. History of AF or atrial flutter as defined by:

(i) AF or atrial flutter on a 12 lead ECG at enrollment, and not due to a reversible cause, or (ii) AF or atrial flutter documented on two separate occasions, not due to a reversible cause, at least 1 day apart prior to enrollment. AF or atrial flutter may be documented by ECG, or as an episode lasting at least 30 seconds on a rhythm strip or Holter recording, or more than 30 minutes if using pacemaker or implantable cardioverter defibrillator (ICD) recordings, or (iii) AF or atrial flutter documented on one occasion, not due to a reversible cause, prior to enrollment and being treated with an oral anticoagulant for AF or atrial flutter at enrollment. [AF or atrial flutter may be documented by ECG, or as an episode lasting at least 30 seconds on a rhythm strip or Holter recording, or more than 30 minutes if using pacemaker or implantable cardioverter defibrillator (ICD) recordings, or mentioned in the medical record], or (iv) AF or atrial flutter documented on one occasion on ECG, not due to a reversible cause, prior to enrollment and at least one more episode of AF or atrial flutter mentioned in the medical record, or (v) AF or atrial flutter documented on one occasion in a cardiologist report, not due to a reversible condition, prior to enrollment.

4. Satisfying CHADS-65 criteria: i) Age =65 or ii) Age <65 and one of: hypertension, diabetes mellitus, congestive heart failure, stroke/transient ischemic attack or peripheral embolism.

Exclusion Criteria:

1. Moderate or severe mitral stenosis.

2. Conditions other than non-valvular atrial fibrillation that require oral anticoagulation, such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism.

3. Need for aspirin at a dose > 165 mg a day, or need for aspirin in combination with P2Y12 antagonist therapy.

4. Need for an interacting drug which precludes the safe use of apixaban.

5. Life expectancy < 6 months.

6. Scheduled live-donor kidney transplant in the next 6 months.

7. A woman who is pregnant or breastfeeding or unwilling to pursue methods of contraception if < 12 months since the last menstrual period.

8. Co-enrollment in a clinical trial where the intervention is deemed to interfere with the adherence, safety or efficacy of the intervention provided herein.

9. Patient's attending physician(s) (e.g., nephrologist and/or cardiologist and/or neurologist) believes that oral anticoagulation is absolutely mandated.

10. Patient's attending physician(s) (e.g., nephrologist and/or cardiologist and/or neurologist) believes that oral anticoagulation is absolutely contraindicated.

Related Conditions & MeSH terms

• Atrial Fibrillation
• End Stage Renal Failure on Dialysis
• Kidney Failure, Chronic

Intervention

Drug:
• Warfarin
Individuals randomized to this arm will be exposed to dose-adjusted daily warfarin targeting an international normalized ratio (INR) of 2.0-3.0.
• Apixaban
Individuals randomized to this arm will receive apixaban 5 mg twice daily (a reduced dose of 2.5 mg twice daily will be given to selected participants).

Other:
• No oral anticoagulation
No oral anticoagulation

Locations

Country	Name	City	State
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	St. George Hospital	Sydney
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Nova Scotia Health Authority, QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Kingston Health Sciences Centre - Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	Hôpital du Sacré-Cœur de Montréal	Montréal	Quebec
Canada	Hôpital Maisonneuve-Rosemont	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Halton Healthcare - Oakville Trafalgar Memorial Hospital	Oakville	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	The Ottawa Hospital - Riverside Campus	Ottawa	Ontario
Canada	CHU de Québec - Université Laval	Quebec City	Quebec
Canada	Regina General Hospital	Regina	Saskatchewan
Canada	Health Sciences North	Sudbury	Ontario
Canada	Surrey Memorial Hospital	Surrey	British Columbia
Canada	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	St. Joseph's Health Centre Toronto	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Unity Health Toronto, at its St. Michael's Hospital site	Toronto	Ontario
Canada	University Health Network - Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Seven Oaks General Hospital	Winnipeg	Manitoba

Sponsors (3)

Lead Sponsor	Collaborator
Unity Health Toronto	Canadian Institutes of Health Research (CIHR), The George Institute for Global Health (Sydney, Australia)

Countries where clinical trial is conducted

Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment of the target population within 2 years		2 years from start of trial
Primary	At least 80% of randomized participants remain in the trial and on the allocated study treatment at the end of the 26-week study period.		26 weeks
Secondary	Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%.		26 weeks
Secondary	>95% of randomized patients adhere to the enrollment criteria with respect to atrial fibrillation or atrial flutter	Through adjudication of ECGs or other cardiac diagnostics	End of trial
Secondary	Major bleeding	As defined by the International Society of Thrombosis and Haemostasis (ISTH)	26 weeks
Secondary	Clinically relevant non-major bleeding	As defined by the International Society of Thrombosis and Haemostasis (ISTH)	26 weeks
Secondary	Stroke and systemic embolism		26 weeks
Secondary	All cause mortality		26 weeks
Secondary	Non-fatal myocardial infarction		26 weeks
Secondary	Vascular events not related to dialysis access		26 weeks
Secondary	Events of special interest related to dialysis access, the dialysis procedure or the oral anticoagulants	Thrombosis of fistula or graft; fistula or graft abandonment; thrombosis of dialysis catheter; red blood cell transfusions; calciphylaxis	26 weeks