DAN-WAR-D - Danish Warfarin-Dialysis Study: Safety and efficacy of warfarin in patients with atrial fibrillation on dialysis -A nationwide parallel-group open randomized clinical trial

2022-502500-75-00 Protocol 02022018 Therapeutic use (Phase IV) Ongoing, recruiting

Start 30 Jan 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 13 sites · Protocol 02022018

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 718
Countries 1
Sites 13

Atrial fibrillation

To investigate the safety and efficacy of warfarin in patients with atrial fibrillation on dialysis

Key facts

Sponsor
Rigshospitalet
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
30 Jan 2024 → ongoing
Decision date (initial)
2023-01-11
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Augustinus foundation

External identifiers

EU CT number
2022-502500-75-00
WHO UTN
U0000-0000-0000
ClinicalTrials.gov
NCT03862859
ISRCTN
ISRCTN00000000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To investigate the safety and efficacy of warfarin in patients with atrial fibrillation on dialysis

Secondary objectives 1

  1. To investigate the association between warfarin and other predefined outcomes

Conditions and MedDRA coding

Atrial fibrillation

VersionLevelCodeTermSystem organ class
21.1 LLT 10008831 Chronic ambulatory peritoneal dialysis 10042613
21.1 LLT 10066623 Chronic haemodialysis 10042613
20.0 LLT 10003660 Atrial fibrillation and flutter 10007541

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Trial phase
Patients are randomized to treatment with warfarin or no treatment
 Randomised Controlled None No treatment: Patients not treated with anticoagulation
Warfarin treatment: Patients treated with warfarin (INR 2-3)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. >=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 (>2 months) prevalent paroxysmal, persistent or permanent atrial fibrillation as documented an electrocardiogram or an episode of ≥30 seconds on Holter monitor, or episodes ≥ 6 minutes on event recorders or any other recording device.

Exclusion criteria 24

  1. CHA2DS2-VASc Score ≤1
  2. 2. Other indications for oral anticoagulation treatment (pulmonary embolism < 6months, deep vein thrombosis <3months, previous pulmonary embolism and/or deep vein thrombosis with life-long indication for oral anticoagulation, prior atrial fibrillation with proven non-tolerance of oral anticoagulation interruption, mechanical heart valve prosthesis) - irrespective of whether treatment is implemented
  3. Ongoing dual antiplatelet treatment
  4. 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
  5. Endoscopy with gastrointestinal ulcer <1 month
  6. Esophageal varices
  7. Autoimmune og genetic coagulation disorders
  8. Congenital alactasia, Lapp Lactase deficiency or glucose-galactose malabsorption
  9. Pending spinal tap
  10. Cerebrovascular malformations
  11. Arterial aneurisms
  12. Ulcers or wounds (Wagner grad >1)
  13. Bacterial endocarditis < 3 months
  14. Active bleeding contraindicating anticoagulation
  15. Any non-elective and/or non-ambulant surgery <7 days
  16. Cerebral hemorrhage <4 weeks
  17. Thrombocytopenia (platelet count <100 × 109/L) <30 days.
  18. Severe liver insufficiency (spontaneous international normalized ratio >1.5) <30 days.
  19. Known intolerance to warfarin
  20. Use of hypericum perforatum / St. John’s Wort
  21. Uncontrolled hypertension (repeat blood pressure >180/110mmhg) < 30 days
  22. Uncontrolled hyperthyroidism (thyroid-stimulating hormone <0.1μIU/mL) <30 days
  23. Pregnancy or lactation
  24. Participation in other ongoing intervention trials adjudged to influence study outcomes

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. any transient ischemic attack, ischemic or unspecified stroke or death due to a transient ischemic attack, ischemic or unspecified stroke will be compared between patients allocated warfarin and no treatment.

Secondary endpoints 1

  1. major bleeding defined in accordance with the International Society on Thrombosis and Hemostasis definition pertaining to major bleeding in non-surgical patients, i.e. major intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, intramuscular with compartment syndrome, or gastrointestinal bleeding.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Warfarin Teva 2.5 mg Tablets

PRD3302213 · Product

Active substance
Warfarin Sodium
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
00 g gram(s)
Max treatment duration
100 Month(s)
Authorisation status
Authorised
ATC code
B01AA03 — WARFARIN
Marketing authorisation
PA 2050/001/004
MA holder
SUN PHARMACEUTICAL INDUSTRIES EUROPE B.V.
MA country
Ireland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

94 Total trials 54 Recruiting 24 Ended
Academic / Non-commercial
Sponsor organisation
Rigshospitalet
Address
Blegdamsvej 9
City
Copenhagen Oe
Postcode
2100
Country
Denmark

Scientific contact point

Organisation
Rigshospitalet
Contact name
Nicholas Carlson

Public contact point

Organisation
Rigshospitalet
Contact name
Nicholas Carlson

Third parties 1

OrganisationCity, countryDuties
Frederiksberg Hospital
ORG-100028217
 Frederiksberg, Denmark On site monitoring

Sponsor responsibilities

Article 77 compliance
Rigshospitalet
Contact point sponsor
Rigshospitalet
Article 77 implementation
Rigshospitalet

Locations

1 EU/EEA country · 13 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruiting 718 13
Rest of world — 0 —

Investigational sites

Denmark

13 sites · Ongoing, recruiting
Nordsjaellands Hospital
Nephrology, Dyrehavevej 29, 3400, Hillerød
Department of Medicine, Bornholm Hospital
Medicine, Department of Medicine, Bornholm Hospital, Roenne
Sydvestjysk Sygehus
Medicine, Finsensgade 35, 6700, Esbjerg
Soenderborg Sygehus
Medicine, Sydvang 1, 6400, Sønderborg
Regionshospitalet Godstrup
Medicine, Hospitalsparken 15, 7400, Herning
Zealand University Hospital
Medicine, Sygehusvej 10, 4000, Roskilde
Lillebaelt Hospital
Medicine, Sygehusvej 24, 6000, Kolding
Aarhus University Hospital
Nephrology, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Rigshospitalet
Nephrology, Blegdamsvej 9, 2100, Copenhagen Oe
Aalborg University Hospital
Nephrology, Moelleparkvej 4, 9000, Aalborg
Holbaek Sygehus
Medicine, Smedelundsgade 60, 4300, Holbæk
Viborg Regional Hospital
Medicine, Heibergs Alle 4, 8800, Viborg
Herlev Hospital
Nephrology, Borgmester Ib Juuls Vej 31, 2730, Herlev

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2024-01-30 2024-01-30

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) v128 DANWARD protocol_w trackchanges 128
Protocol (for publication) v128 DANWARD protocolclean 128
Recruitment arrangements (for publication) recruitment 1
Subject information and informed consent form (for publication) v118 DanWarD Patientinformation m informeret samtykke_clean 118
Summary of Product Characteristics (SmPC) (for publication) see Produktresume Marevan 1
Synopsis of the protocol (for publication) Protokolresume 1

Application history

7 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2022-12-01 Denmark Acceptable
2023-01-11
 2023-01-11
2 SUBSTANTIAL MODIFICATION SM-1 2023-02-17 Denmark Acceptable
2023-03-03
 2023-03-03
3 SUBSTANTIAL MODIFICATION SM-2 2023-06-13
4 SUBSTANTIAL MODIFICATION SM-3 2023-11-10 Denmark Acceptable 2024-01-29
5 SUBSTANTIAL MODIFICATION SM-4 2024-12-11 Denmark Acceptable
2025-02-14
 2025-02-17
6 NON SUBSTANTIAL MODIFICATION NSM-4 2025-11-10 Denmark Acceptable
2025-02-14
 2025-11-10
7 NON SUBSTANTIAL MODIFICATION NSM-5 2026-03-27 Denmark Acceptable
2025-02-14
 2026-03-27

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