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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03987711




Registration number
NCT03987711
Ethics application status
Date submitted
12/06/2019
Date registered
17/06/2019
Date last updated
1/12/2020

Titles & IDs
Public title
Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis
Scientific title
Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis (SAFE-D)
Secondary ID [1] 0 0
SAFE-D-01
Universal Trial Number (UTN)
Trial acronym
SAFE-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 0 0
End Stage Renal Failure on Dialysis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Warfarin
Treatment: Drugs - Apixaban
Other interventions - No oral anticoagulation

Experimental: 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.

Active Comparator: 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).

Active Comparator: No oral anticoagulation - Individuals in this arm will be exposed to a treatment strategy in which no oral anticoagulation is prescribed.


Treatment: Drugs: 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.

Treatment: Drugs: 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 interventions: No oral anticoagulation
No oral anticoagulation

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recruitment of the target population within 2 years
Timepoint [1] 0 0
2 years from start of trial
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
26 weeks
Secondary outcome [1] 0 0
Proportion of patients randomized to warfarin achieving a Time in the Therapeutic Range (TTR) >65%.
Timepoint [1] 0 0
26 weeks
Secondary outcome [2] 0 0
>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
Timepoint [2] 0 0
End of trial
Secondary outcome [3] 0 0
Major bleeding - As defined by the International Society of Thrombosis and Haemostasis (ISTH)
Timepoint [3] 0 0
26 weeks
Secondary outcome [4] 0 0
Clinically relevant non-major bleeding - As defined by the International Society of Thrombosis and Haemostasis (ISTH)
Timepoint [4] 0 0
26 weeks
Secondary outcome [5] 0 0
Stroke and systemic embolism
Timepoint [5] 0 0
26 weeks
Secondary outcome [6] 0 0
All cause mortality
Timepoint [6] 0 0
26 weeks
Secondary outcome [7] 0 0
Non-fatal myocardial infarction
Timepoint [7] 0 0
26 weeks
Secondary outcome [8] 0 0
Vascular events not related to dialysis access
Timepoint [8] 0 0
26 weeks
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
26 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The George Institute for Global Health - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Nova Scotia
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Canada
State/province [4] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
St. Michael's Hospital, Toronto
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Canadian Institutes of Health Research (CIHR)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The George Institute for Global Health (Sydney, Australia)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03987711
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ziv Harel
Address 0 0
St. Michael's Hospital, Toronto
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ziv Harel
Address 0 0
Country 0 0
Phone 0 0
416-360-4000
Fax 0 0
Email 0 0
ziv.harel@unityhealth.to
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03987711