Back to results

The Danish Warfarin-Dialysis Study - Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis (DANWARD)

Primary Purpose

Atrial Fibrillation and Flutter, Stroke, Major Bleed

Status

Recruiting

Phase

Phase 4

Locations

Denmark

Study Type

Interventional

Intervention

Warfarin

About this trial

This is an interventional prevention trial for Atrial Fibrillation and Flutter

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients ≥18 years on chronic dialysis due to end-stage renal disease with de novo diagnosis of non-valvular paroxysmal, persistent, or permanent atrial fibrillation OR non-treated (for >2 months) prevalent paroxysmal, persistent or permanent atrial fibrillation as documented by an electrocardiogram or an episode of ≥30 seconds on Holter monitor, or episodes ≥ 6 minutes on event recorders or any other recording device.
Competence to understand the study rationale, including potential risks and benefits associated with treatment, necessary for written informed consent.

Exclusion Criteria:

CHA2DS2-VASc Score ≤1
Other indications for oral anticoagulation treatment (pulmonary embolism < 6 months, deep vein thrombosis <3 months, prior atrial fibrillation, mechanical heart valve prosthesis) irrespective of whether treatment is implemented
Ongoing dual antiplatelet treatment
Malignancy (with exception of non-melanoma skin cancer) with recent < 1 year, ongoing, or planned curative, or palliative chemo- , radiation-, and/or scheduled surgical therapy
Endoscopy with gastrointestinal ulcer <1 month
Esophageal varices
Autoimmune og genetic coagulation disorders
Congenital alactasia, Lapp Lactase deficiency or glucose-galactose malabsorption
Pending spinal tap
Cerebrovascular malformations
Arterial aneurysms
Ulcers or wounds (Wagner grad >1)
Bacterial endocarditis < 3 months
Active bleeding contraindicating anticoagulation
Any non-elective and/or non-ambulant surgery <7 days
Cerebral hemorrhage <4 weeks
Thrombocytopenia (platelet count <100 × 109/L) <30 days.
Severe liver insufficiency (spontaneous international normalized ratio >1.5) <30 days.
Known intolerance to warfarin
Use of hypericum perforatum / St. John's Wort
Uncontrolled hypertension (repeat blood pressure >180/110 mmhg) < 30 days
Uncontrolled hyperthyroidism (thyroid-stimulating hormone <0.1μIU/mL) <30 days
Pregnancy or lactation
Participation in other ongoing intervention trials adjudged to influence study outcomes

Sites / Locations

Aalborg University HosptialRecruiting
Aarhus University Hospital
Department of Nephrology, Copenhagen University Hospital RigshospitaletRecruiting
Department of Nephrology, Herlev HospitalRecruiting
Department of nephrology, Nordsjaellands HospitalRecruiting
Holbaek HospitalRecruiting
Holstebro HospitalRecruiting
Lillebælt HospitalRecruiting
Zealand University HospitalRecruiting
Bornholms HospitalRecruiting
Hospital SønderjyllandRecruiting
Viborg Regional HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Treatment with Warfarin

No treatment

Arm Description

Warfarin with dosing targeting an international normalized ratio of 2-3.

No treatment

Outcomes

Primary Outcome Measures

Primary efficacy outcome - Number of participants with transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke

Any transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke or death attributable to either ischemic or undefined stroke

Primary safety outcome - Number of participants with fatal or non-fatal major bleeding

Any major bleeding as defined in accordance with the International Society on Thrombosis and Hemostasis definition pertaining to major bleeding in non-surgical patients

Secondary Outcome Measures

Number of participants with ischemic or unspecified stroke

Any non-fatal or fatal ischemic stroke or unspecified stroke event

Number of participants with ischemic stroke

Any non-fatal or fatal ischemic stroke event

Number of participants with hemorrhagic stroke

Any non-fatal or fatal hemorrhagic stroke event

Number of participants with ischemic or hemorrhagic stroke

Any non-fatal or fatal ischemic or hemorrhagic stroke event

Number of deaths

All-cause mortality

The combination of any non-fatal stroke and all-cause mortality

Number of participants with either non-fatal ischemic or hemorrhagic stroke of death due to any cause

The combination of any non-fatal stroke, any non-fatal major bleeding, and all-cause mortality

Number of participants with either non-fatal ischemic or hemorrhagic stroke, any non-fatal major bleeding as defined in accordance with the International Society on Thrombosis and Hemostasis definition pertaining to major bleeding in non-surgical patients, or death due to any cause

Full Information

NCT ID

NCT03862859

First Posted

February 22, 2019

Last Updated

March 13, 2023

Sponsor

Nicholas Carlson

Collaborators

Danish Heart Foundation

1. Study Identification

Unique Protocol Identification Number

NCT03862859

Brief Title

The Danish Warfarin-Dialysis Study - Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis

Acronym

DANWARD

Official Title

The Danish Warfarin-Dialysis Study: Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis - A Nationwide Parallel-group Open Randomized Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 9, 2019 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Nicholas Carlson

Collaborators

Danish Heart Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study aims to evaluate the appropriateness of initiating oral anticoagulation for stroke risk reduction in dialysis populations with atrial fibrillation. Specifically, the study will assess the overall safety, tolerability, and efficacy of initiating treatment with Warfarin in patients with end-stage renal disease on dialysis and atrial fibrillation.

Detailed Description

Data pertaining to the tolerability, safety, and benefit of initiating anticoagulation for stroke risk reduction in patients with end-stage renal disease and atrial fibrillation remains conflicting and insufficient. Patients on dialysis continue to be routinely excluded from randomized controlled trials, and evidence from observational studies is plausibly biased. The main objective of the following parallel-group open randomized clinical trial presents a nationwide study aimed at investigating the benefit, tolerability, and safety of initiating warfarin versus no treatment in patients with atrial fibrillation on dialysis. The anticipated results from this project will provide conclusive evidence as to the appropriateness of initiating oral anticoagulation for stroke risk reduction in dialysis populations with atrial fibrillation with direct effects on clinical management and international guidelines pertaining to these patients. The study is planned as a multicentre, randomized, open label, parallel group trial with planned inclusion of a total of 718 patients (359 patients per arm). Dialysis-treated patients with end-stage renal disease with paroxysmal, persistent, or permanent atrial fibrillation will be enrolled and randomized to either treatment with warfarin or no treatment. Randomization with be attained using a 1:1 allocation as per a computer-generated randomization schedule stratified by gender, age by decade, and center using permuted blocks of random sizes. Study participants will be allocated to treatment in accordance with the randomization for the full duration of the trial i.e. at a minimum one year following randomization, and followed with regular monitoring for the the primary efficacy outcome of ischemic stroke or death due to ischemic or unspecified stroke and the primary safety outcome of major bleeding defined in accordance with the International Society on Thrombosis and Hemostasis definition.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atrial Fibrillation and Flutter, Stroke, Major Bleed, End-stage Renal Disease

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

A multicentre, randomized, open label, parallel group study.

Masking

None (Open Label)

Masking Description

None (Open Label

Allocation

Randomized

Enrollment

718 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment with Warfarin

Arm Type

Active Comparator

Arm Description

Warfarin with dosing targeting an international normalized ratio of 2-3.

Arm Title

No treatment

Arm Type

No Intervention

Arm Description

No treatment

Intervention Type

Drug

Intervention Name(s)

Warfarin

Other Intervention Name(s)

Coumadin, Marevan, Jantoven

Intervention Description

Dose adjusted Warfarin targeting an international normalized ratio of 2-3.

Primary Outcome Measure Information:

Title

Primary efficacy outcome - Number of participants with transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke

Description

Any transient ischemic attack, fatal and non-fatal ischaemic or unspecific stroke or death attributable to either ischemic or undefined stroke

Time Frame

From randomization to end of observation - up to 4 years

Title

Primary safety outcome - Number of participants with fatal or non-fatal major bleeding

Description

Any major bleeding as defined in accordance with the International Society on Thrombosis and Hemostasis definition pertaining to major bleeding in non-surgical patients

Time Frame

From randomization to end of observation - up to 4 years

Secondary Outcome Measure Information:

Title

Number of participants with ischemic or unspecified stroke

Description

Any non-fatal or fatal ischemic stroke or unspecified stroke event

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of participants with ischemic stroke

Description

Any non-fatal or fatal ischemic stroke event

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of participants with hemorrhagic stroke

Description

Any non-fatal or fatal hemorrhagic stroke event

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of participants with ischemic or hemorrhagic stroke

Description

Any non-fatal or fatal ischemic or hemorrhagic stroke event

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of deaths

Description

All-cause mortality

Time Frame

From time of randomization to end of observation - up to 4 years

Title

The combination of any non-fatal stroke and all-cause mortality

Description

Number of participants with either non-fatal ischemic or hemorrhagic stroke of death due to any cause

Time Frame

From time of randomization to end of observation - up to 4 years

Title

The combination of any non-fatal stroke, any non-fatal major bleeding, and all-cause mortality

Description

Time Frame

From time of randomization to end of observation - up to 4 years

Other Pre-specified Outcome Measures:

Title

Discontinuation of the allocated randomized therapy

Description

Number of participants discontinuing the allocated randomized therapy irrespective of cause

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of participants with peripheral artery disease

Description

Any diagnosis of previously unverified peripheral artery disease

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of participants with fatal or non-fatal acute myocardial infarction

Description

Any non-fatal or fatal acute myocardial infarction event

Time Frame

From randomization to end of observation - up to 4 years

Title

Number of participants with calciphylaxis

Description

Development of calciphylaxis as defined by clinical diagnosis

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Number of participants hospitalized due to left-sided heart failure

Description

Any hospitalization due to left-sided heart failure as defined by de novo LVEF <30% with echocardiographic verification

Time Frame

From time of randomization to end of observation - up to 4 years

Title

Percentage of participants with arteriovenous fistula thrombosis

Description

Arteriovenous fistula thrombosis in participants dialyzed via an arteriovenous fistula

Time Frame

From randomization to end of observation - up to 4 years

Title

Number of participants with osteoporotic fractures

Description

Osteoporotic fractures as defined by low energy fractures of the proximal femur, distal radius, humerus, pelvis, and vertebrae

Time Frame

From randomization to end of observation - up to 4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients ≥18 years on chronic dialysis due to end-stage renal disease Non-valvular paroxysmal, persistent, or permanent atrial fibrillation OR non-treated (for >2 months) prevalent paroxysmal, persistent or permanent atrial fibrillation as documented by an electrocardiogram or an episode of ≥30 seconds on Holter monitor, or episodes ≥ 6 minutes on event recorders or any other recording device. Competence to understand the study rationale, including potential risks and benefits associated with treatment, necessary for written informed consent. Exclusion Criteria: CHA2DS2-VASc Score ≤1 Other indications for oral anticoagulation treatment (pulmonary embolism < 6 months, deep vein thrombosis <3 months, prior atrial fibrillation, mechanical heart valve prosthesis) irrespective of whether treatment is implemented Ongoing dual antiplatelet treatment Malignancy (with exception of non-melanoma skin cancer) with recent < 1 year, ongoing, or planned curative, or palliative chemo- , radiation-, and/or scheduled surgical therapy Endoscopy with gastrointestinal ulcer <1 month Esophageal varices Autoimmune og genetic coagulation disorders Congenital alactasia, Lapp Lactase deficiency or glucose-galactose malabsorption Pending spinal tap Cerebrovascular malformations Arterial aneurysms Ulcers or wounds (Wagner grad >1) Bacterial endocarditis < 3 months Active bleeding contraindicating anticoagulation Any non-elective and/or non-ambulant surgery <7 days Cerebral hemorrhage <4 weeks Thrombocytopenia (platelet count <100 × 109/L) <30 days. Severe liver insufficiency (spontaneous international normalized ratio >1.5) <30 days. Known intolerance to warfarin Use of hypericum perforatum / St. John's Wort Uncontrolled hypertension (repeat blood pressure >180/110 mmhg) < 30 days Uncontrolled hyperthyroidism (thyroid-stimulating hormone <0.1μIU/mL) <30 days Pregnancy or lactation Participation in other ongoing intervention trials adjudged to influence study outcomes

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nicholas Carlson, MD PhD

Phone

+45 35455827

nicholas.carlson.01@regionh.dk

First Name & Middle Initial & Last Name or Official Title & Degree

Gunnar H Gislason, Prof MD PhD

Phone

+45 70 25 00 00

Gunnar.Gislason@regionh.dk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicholas Carlson, MD PhD

Organizational Affiliation

Department of Nephrology, Copenhagen University Hospital Rigshospitalet

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gunnar H Gislason, Prof MD PhD

Organizational Affiliation

Danish Heart Foundation

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Anne-Lise Kamper, MD DMSc

Organizational Affiliation

Department of Nephrology, Copenhagen University Hospital Rigshospitalet

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Christian Torp-Pedersen, Prof MD DMSc

Organizational Affiliation

Department of Cardiology, North Zealand Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jonas B Olesen, MD PhD

Organizational Affiliation

Department of Cardiology, Copenhagen University Hospital Gentofte

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Casper Bang, MD PhD

Organizational Affiliation

Department of Cardiology, Frederiksberg and Bispebjerg Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Thomas A Gerds, Prof

Organizational Affiliation

Danish Heart Foundation

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Ditte Hansen, MD PhD

Organizational Affiliation

Department of Nephrology, Copenhagen University Hospital Herlev

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Morten Schou, Prof MD PhD

Organizational Affiliation

Department of Cardiology, Copenhagen University Hospital Herlev

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Mads Hornum, Prof MD PhD

Organizational Affiliation

Department of Nephrology, Copenhagen University Hospital Rigshospitalet

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Erik Grove, MD PhD

Organizational Affiliation

Department of Cardiology, Aarhus University Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jens D Jensen, MD PhD

Organizational Affiliation

Department of Nephrology, Aarhus University Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Ellen Linnea F Ballegaard, MD

Organizational Affiliation

Department of Nephrology, Copenhagen University Hospital Rigshospitalet

Official's Role

Study Chair

Facility Information:

Facility Name

Aalborg University Hosptial

City

Aalborg

ZIP/Postal Code

9100

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jesper M Rantanen, MD PhD

jemr@rn.dk

Facility Name

Aarhus University Hospital

City

Aarhus

ZIP/Postal Code

8200

Country

Denmark

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christian D Peters, MD PhD

chipte@rm.dk

Facility Name

Department of Nephrology, Copenhagen University Hospital Rigshospitalet

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nicholas Carlson, MD PhD

Phone

+45 35455927

nicholas.carlson.01@regionh.dk

First Name & Middle Initial & Last Name & Degree

Nicholas Carlson, MD PhD

Facility Name

Department of Nephrology, Herlev Hospital

City

Herlev

ZIP/Postal Code

2730

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kristine Lindhard Rasmussen, MD

kristine.lindhard.rasmussen@regionh.dk

First Name & Middle Initial & Last Name & Degree

Kristine Lindhard Rasmussen, MD

Facility Name

Department of nephrology, Nordsjaellands Hospital

City

Hillerød

ZIP/Postal Code

3400

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marianne Bertelsen, MD

marianne.camilla.bertelsen@regionh.dk

First Name & Middle Initial & Last Name & Degree

Marianne Bertelsen, MD

Facility Name

Holbaek Hospital

City

Holbæk

ZIP/Postal Code

4300

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Morten Lindhardt, MD PhD

moli@regionsjaelland.dk

Facility Name

Holstebro Hospital

City

Holstebro

ZIP/Postal Code

7500

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Frank H Mose, MD PhD

frank.holden.christensen@vest.rm.dk

Facility Name

Lillebælt Hospital

City

Kolding

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Donata Cibulskyte-Ninkovic, MD

donata.cibulskyte-ninkovic@rsyd.dk

Facility Name

Zealand University Hospital

City

Roskilde

ZIP/Postal Code

4000

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rikke Borg, MD PhD

rbor@regionsjaelland.dk

First Name & Middle Initial & Last Name & Degree

Lene Boesby, MD PhD

Facility Name

Bornholms Hospital

City

Rønne

ZIP/Postal Code

3700

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Finn T Nielsen, MD

finnthomsen.nielsen@regionh.dk

Facility Name

Hospital Sønderjylland

City

Sønderborg

ZIP/Postal Code

6400

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jan D Kampmann, MD

jdk@rsyd.dk

Facility Name

Viborg Regional Hospital

City

Viborg

ZIP/Postal Code

8800

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ida Tietze, MD PhD

ida@tietze.dk

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual participant data for primary and secondary outcomes measures will be made available

IPD Sharing Time Frame

Data will be available within 12 months of study completion

IPD Sharing Access Criteria

Data access requests will be reviewed, requestors will be required to sign a Data Access Agreement.

Learn more about this trial

The Danish Warfarin-Dialysis Study - Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis

We'll reach out to this number within 24 hrs