Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis

NCT03987711 | Completed Phase 2 DMC

• 1 other identifier: SAFE-D-01
• Study Type: interventional
• Target: 151
• Locations: 2 countries
• Sites: 28

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).

Conditions

Atrial Fibrillation; End Stage Renal Failure on Dialysis

Outcome Measures

Primary Outcomes (2)

• Recruitment of the target population within 2 years

  2 years from start of trial

• 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 Outcomes (9)

• Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%.

  26 weeks

• >95% of randomized patients adhere to the enrollment criteria with respect to atrial fibrillation or atrial flutter

  End of trial

• Major bleeding

  26 weeks

• Clinically relevant non-major bleeding

  26 weeks

• Stroke and systemic embolism

  26 weeks

Study Arms (3)

Warfarin

EXPERIMENTAL

Individuals randomized to this arm will be exposed to dose-adjusted daily warfarin targeting an international normalized ratio (INR) of 2.0-3.0.

Drug: Warfarin

Apixaban

ACTIVE COMPARATOR

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).

Drug: Apixaban

No oral anticoagulation

ACTIVE COMPARATOR

Individuals in this arm will be exposed to a treatment strategy in which no oral anticoagulation is prescribed.

Other: No oral anticoagulation

Interventions

Warfarin DRUG

Individuals randomized to this arm will be exposed to dose-adjusted daily warfarin targeting an international normalized ratio (INR) of 2.0-3.0.

Also known as: Coumadin

Warfarin

Apixaban DRUG

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).

Also known as: Eliquis

Apixaban

No oral anticoagulation OTHER

No oral anticoagulation

No oral anticoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Receiving maintenance hemodialysis or peritoneal dialysis for \> 90 days.
• 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.
• 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.

You may not qualify if:

• Moderate or severe mitral stenosis.
• Conditions other than non-valvular atrial fibrillation that require oral anticoagulation, such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism.
• Need for aspirin at a dose \> 165 mg a day, or need for aspirin in combination with P2Y12 antagonist therapy.
• Need for an interacting drug which precludes the safe use of apixaban.
• Life expectancy \< 6 months.
• Scheduled live-donor kidney transplant in the next 6 months.
• A woman who is pregnant or breastfeeding or unwilling to pursue methods of contraception if \< 12 months since the last menstrual period.
• Co-enrollment in a clinical trial where the intervention is deemed to interfere with the adherence, safety or efficacy of the intervention provided herein.
• Patient's attending physician(s) (e.g., nephrologist and/or cardiologist and/or neurologist) believes that oral anticoagulation is absolutely mandated.
• Patient's attending physician(s) (e.g., nephrologist and/or cardiologist and/or neurologist) believes that oral anticoagulation is absolutely contraindicated.

Sponsors & Collaborators

• Unity Health Toronto: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• The George Institute for Global Health (Sydney, Australia): collaborator

Study Sites (28)

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

St. George Hospital

Sydney, Australia

Location

Surrey Memorial Hospital

Surrey, British Columbia, V3V 0C6, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Seven Oaks General Hospital

Winnipeg, Manitoba, R2V 3M3, Canada

Location

Nova Scotia Health Authority, QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Kingston Health Sciences Centre - Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Halton Healthcare - Oakville Trafalgar Memorial Hospital

Oakville, Ontario, L6M 0L8, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

The Ottawa Hospital - Riverside Campus

Ottawa, Ontario, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4G 3E8, Canada

Location

Unity Health Toronto, at its St. Michael's Hospital site

Toronto, Ontario, M5B 1W8, Canada

Location

University Health Network - Toronto General Hospital

Toronto, Ontario, M6K3S2, Canada

Location

St. Joseph's Health Centre Toronto

Toronto, Ontario, M6R 1B5, Canada

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hôpital du Sacré-Cœur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

McGill University Health Centre

Montreal, Quebec, H8S 4K4, Canada

Location

CHU de Québec - Université Laval

Québec, Quebec, G1R 2J6, Canada

Location

Regina General Hospital

Regina, Saskatchewan, S4P 0W5, Canada

Location

Related Publications (1)

• Harel Z, Smyth B, Badve SV, Blum D, Beaubien-Souligny W, Silver SA, Clark E, Suri R, Mavrakanas TA, Sasal J, Prasad B, Eikelboom J, Tennankore K, Rigatto C, Prce I, Madore F, Mac-Way F, Steele A, Zeng Y, Sholzberg M, Dorian P, Yan AT, Sood MM, Gladstone DJ, Tseng E, Kitchlu A, Walsh M, Sapir D, Oliver MJ, Krishnan M, Kiaii M, Wong N, Kotwal S, Battistella M, Acedillo R, Lok C, Weir M, Wald R. Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial. J Am Soc Nephrol. 2025 May 1;36(5):901-910. doi: 10.1681/ASN.0000000000000495. Epub 2024 Nov 4.

  PMID: 39495569 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Warfarin; apixaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ziv Harel

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• Ron Wald

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 17, 2019
• Study Start: December 10, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: June 22, 2023

Record last verified: 2023-06

Locations

AU (4); CA (24)