Clinical trial NCT03987711: Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis
Official title: Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis (SAFE-D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
End Stage Renal Failure on Dialysis
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The George Institute for Global Health (Sydney, Australia)
First posted: 2019-06-17
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Recruitment of the target population within 2 years
timeFrame: 2 years from start of trial
measure: 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.
timeFrame: 26 weeks
Secondary outcomes:
measure: Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%.
timeFrame: 26 weeks
measure: >95% of randomized patients adhere to the enrollment criteria with respect to atrial fibrillation or atrial flutter
timeFrame: End of trial
measure: Major bleeding
timeFrame: 26 weeks
measure: Clinically relevant non-major bleeding
timeFrame: 26 weeks
measure: Stroke and systemic embolism
timeFrame: 26 weeks
measure: All cause mortality
timeFrame: 26 weeks
measure: Non-fatal myocardial infarction
timeFrame: 26 weeks
measure: Vascular events not related to dialysis access
timeFrame: 26 weeks
measure: Events of special interest related to dialysis access, the dialysis procedure or the oral anticoagulants
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. George Hospital
city: Surrey
country: Canada
facility: Surrey Memorial Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Seven Oaks General Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Nova Scotia Health Authority, QEII Health Sciences Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre - Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oakville
country: Canada
facility: Halton Healthcare - Oakville Trafalgar Memorial Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Riverside Campus
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto, at its St. Michael's Hospital site
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre Toronto
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Hôpital du Sacré-Cœur de Montréal
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Québec - Université Laval
state: Quebec
city: Regina
country: Canada
facility: Regina General Hospital
state: Saskatchewan
Study officials:
affiliation: Unity Health Toronto
name: Ziv Harel
role: PRINCIPAL_INVESTIGATOR
affiliation: Unity Health Toronto
name: Ron Wald
role: PRINCIPAL_INVESTIGATOR
References: