Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis

Phase 2

Completed

• Conditions: Atrial Fibrillation; End Stage Renal Failure on Dialysis
• Interventions: Drug: Warfarin; Drug: Apixaban; Other: No oral anticoagulation

• Registration Number: NCT03987711
• Lead Sponsor: Unity Health Toronto

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-12
• Study First Submitted QC: 2019-06-12
• Study First Posted: 2019-06-17
• Study Start: 2019-12-10
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-19
• Last Update Posted: 2023-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 151

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Warfarin	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	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).
No oral anticoagulation	No oral anticoagulation	Individuals in this arm will be exposed to a treatment strategy in which no oral anticoagulation is prescribed.

Primary Outcome Measures

Name	Time	Method
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
Recruitment of the target population within 2 years	2 years from start of trial

Secondary Outcome Measures

Name	Time	Method
Non-fatal myocardial infarction	26 weeks
>95% of randomized patients adhere to the enrollment criteria with respect to atrial fibrillation or atrial flutter	End of trial	Through adjudication of ECGs or other cardiac diagnostics
Major bleeding	26 weeks	As defined by the International Society of Thrombosis and Haemostasis (ISTH)
Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%.	26 weeks
Clinically relevant non-major bleeding	26 weeks	As defined by the International Society of Thrombosis and Haemostasis (ISTH)
Stroke and systemic embolism	26 weeks
Vascular events not related to dialysis access	26 weeks
Events of special interest related to dialysis access, the dialysis procedure or the oral anticoagulants	26 weeks	Thrombosis of fistula or graft; fistula or graft abandonment; thrombosis of dialysis catheter; red blood cell transfusions; calciphylaxis
All cause mortality	26 weeks

Trial Locations

Locations (28)

Prince of Wales Hospital; 🇦🇺 Randwick, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

Health Sciences North; 🇨🇦 Sudbury, Ontario, Canada

Nepean Hospital; 🇦🇺 Kingswood, New South Wales, Australia

Unity Health Toronto, at its St. Michael's Hospital site; 🇨🇦 Toronto, Ontario, Canada

Thunder Bay Regional Health Sciences Centre; 🇨🇦 Thunder Bay, Ontario, Canada

Kingston Health Sciences Centre - Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

Lakeridge Health Oshawa; 🇨🇦 Oshawa, Ontario, Canada

Halton Healthcare - Oakville Trafalgar Memorial Hospital; 🇨🇦 Oakville, Ontario, Canada

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Surrey Memorial Hospital; 🇨🇦 Surrey, British Columbia, Canada

St. George Hospital; 🇦🇺 Sydney, Australia

Seven Oaks General Hospital; 🇨🇦 Winnipeg, Manitoba, Canada

Nova Scotia Health Authority, QEII Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Royal Victoria Regional Health Centre; 🇨🇦 Barrie, Ontario, Canada

The Ottawa Hospital - Riverside Campus; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

University Health Network - Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Hôpital Maisonneuve-Rosemont; 🇨🇦 Montréal, Quebec, Canada

St. Joseph's Health Centre Toronto; 🇨🇦 Toronto, Ontario, Canada

CHU de Québec - Université Laval; 🇨🇦 Quebec City, Quebec, Canada

Jewish General Hospital; 🇨🇦 Montréal, Quebec, Canada

Hôpital du Sacré-Cœur de Montréal; 🇨🇦 Montréal, Quebec, Canada

Regina General Hospital; 🇨🇦 Regina, Saskatchewan, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada