Stroke Prophylaxis With Apixaban in Chronic Kidney Disease Stage 5 Patients With Atrial Fibrillation

NCT05679024 | Recruiting Phase 3 DMC

• 1 other identifier: EU CT 2022-501600-10-00
• Study Type: interventional
• Target: 1,400
• Locations: 4 countries
• Sites: 34

Brief Summary

Objective: To study the efficacy and safety of apixaban as stroke prophylaxis in patients with chronic kidney disease (CKD) stage 5 and atrial fibrillation (AF) with or without dialysis treatment. The study hypothesis is that compared to no anticoagulation, apixaban reduces the incidence of ischemic stroke without causing an unacceptable increase in fatal or intracranial bleeding events. The secondary objectives are to evaluate the risk of all-cause mortality, cardiovascular events, and major bleeding in people with CKD stage 5 and AF treated with apixaban compared to standard of care without anticoagulation. Trial design: Pragmatic Prospective Open Label Randomized Controlled Clinical Trial, phase 3b over 12-72 months. Trial population: 1000-1400 patients at ≈50 sites in Sweden, Finland, Norway, Iceland and Poland Eligibility criteria: Adults ≥18 years with CKD stage 5 (ongoing treatment with any chronic dialysis treatment OR an estimated glomerular filtration rate (eGFR)\* \<20 ml/min/1.73 m2 at least twice 3 months apart of which at least one occasion is \<15 ml/min/1.73 m2 due to CKD during the last 12 months) and a diagnosis of chronic, paroxysmal, persistent, or permanent AF or atrial flutter (AFL) with CHA2DS2-VASc score ≥2 for men or ≥3 or more for women as an indication for oral anticoagulation. The exclusion criteria are AF or AFL due to reversible causes, rheumatic mitral stenosis or moderate-to-severe non-rheumatic mitral stenosis at the time of inclusion into the study, a condition other than AF or AFL that requires chronic anticoagulation, contraindications for anticoagulation, active bleeding or serious bleeding within 3 months, planned for surgery within 3 months, and current use of strong inhibitors of both CYP3A4 and P-glycoprotein. Interventions: Randomization 1:1 to treatment with apixaban 2.5 mg twice daily and standard of care, or standard of care and no anticoagulation. Outcome measures: primary efficacy (time to first ischemic stroke); primary safety (the composite of time to first intracranial bleeding or fatal bleeding); secondary efficacy (time to all-cause mortality, time to cardiovascular event or cardiovascular death); secondary safety (time to first major bleeding according to International Society on Thrombosis and Hemostasis (ISTH) criteria)

Conditions

Chronic Kidney Diseases; Atrial Fibrillation; Stroke; Intracerebral Hemorrhage; Major Bleed; Cardiovascular Complication; Death; Kidney Transplant; Complications; Thromboses, Venous

Keywords

Chronic kidney disease; Hemodialysis; Peritoneal dialysis; Kidney transplantation; Atrial fibrillation; Oral anticoagulation

Outcome Measures

Primary Outcomes (2)

• Ischemic stroke or systemic embolism (efficacy)

  Time to ischemic stroke or systemic embolism

  Up to 72 months

• Intracranial bleeding (including hemorrhagic stroke) and fatal bleeding (safety)

  Time to intracranial or fatal bleeding

  Up to 72 months

Secondary Outcomes (5)

• All-cause mortality

  Up to 72 months

• Cardiovascular event

  Up to 72 months

• Individual components of cardiovascular event

  Up to 72 months

• Major bleeding

  Up to 72 months

• Major bleeding in patients undergoing kidney transplantation

  Up to 72 months

Other Outcomes (3)

• Thromboembolic event

  Up to 72 months

• Dialysis access thrombosis

  Up to 72 months

• Kidney replacement therapy initiation

  Up to 72 months

Study Arms (2)

Apixaban 2.5 mg twice daily and standard of care

ACTIVE COMPARATOR

Apixaban 2.5 mg twice daily (low dose) and all other standard of care

Drug: Apixaban 2.5 milligram Oral Tablet

Standard of care and no anticoagulation

NO INTERVENTION

All other Standard of care and no anticoagulation

Interventions

Apixaban 2.5 milligram Oral Tablet DRUG

Oral Tablet

Apixaban 2.5 mg twice daily and standard of care

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent
• years of age or older
• Ongoing treatment with any chronic dialysis treatment OR an estimated glomerular filtration rate (eGFR)\* \<20 ml/min/1.73 m2 at least twice 3 months apart of which at least one occasion is \<15 ml/min/1.73 m2 due to CKD during the last year (12 months).
• Diagnosis of chronic (i.e., repeated) paroxysmal, persistent, or permanent atrial fibrillation (AF) or atrial flutter (AFL)
• CHA2DS2-VASc score ≥2 or more for men ≥3 or more for women as an indication for oral anticoagulation
• Women of childbearing potential (WOCBP) should have a negative highly effective pregnancy test at screening and must agree to follow instructions for method(s) of contraception for the duration of treatment

You may not qualify if:

• Participants may not be included in the study if any of the following criteria are met:
• AF or AFL due to reversible causes (e.g., thyrotoxicosis, pericarditis)
• Any condition other than AF or AFL that requires chronic anticoagulation (e.g., a prosthetic mechanical heart valve, antiphospholipid syndrome).
• Any contraindication for anticoagulation including
• endocarditis
• documented intolerance for apixaban
• liver disease with documented coagulation disorder
• pregnancy or breast feeding
• Active bleeding or serious bleeding within 3 months, or
• documented hemorrhagic blood dyscrasia
• patients currently receiving dual antiplatelet therapy
• Planned for surgery
• kidney transplantation with a living donor within 3 months
• active on the kidney transplant waiting list at a kidney transplant center where apixaban use is prohibited
• valvular heart disease surgery

Sponsors & Collaborators

• Region Stockholm: lead

Study Sites (34)

Helsingfors University hospital

Helsinki, Finland

RECRUITING

Tampere hospital

Tampere, Finland

RECRUITING

Turku hospital

Turku, Finland

RECRUITING

Landspitali, the National University hospital of Iceland

Reykjavik, Iceland

RECRUITING

Oslo Akershus

Oslo, Norway

RECRUITING

Oslo Universitetssjukhus Ullevål

Oslo, Norway

RECRUITING

Stavanger hospital

Stavanger, Norway

RECRUITING

Tromsö hospital

Tromsø, Norway

RECRUITING

Vestfold hospital

Tønsberg, Norway

ACTIVE NOT RECRUITING

Falun hospital

Falun, Dalarna County, Sweden

RECRUITING

Östersund hospital

Östersund, Jämtland County, Sweden

NOT YET RECRUITING

Lasarettet i Falun

Falun, Region Dalarna, Sweden

RECRUITING

Mora sjukhus

Mora, Region Dalarna, Sweden

RECRUITING

Länssjukhuset Kalmar

Kalmar, Region Kalmar Län, Sweden

NOT YET RECRUITING

Kalix hospital

Kalix, Region Norrbotten, Sweden

RECRUITING

Skånes University hospital Lund

Lund, Region Skåne, Sweden

RECRUITING

Skånes University hospital Malmö

Malmo, Region Skåne, Sweden

RECRUITING

Norrland University hospital Umeå

Umeå, Region Västerbotten, Sweden

RECRUITING

Sundsvall

Sundsvall, Region Västernorrland, Sweden

RECRUITING

Västmanlands sjukhus Västerås

Västerås, Region Västmanland, Sweden

NOT YET RECRUITING

Borås sjukhus

Borås, Region Västra Götaland, Sweden

RECRUITING

Sahlgrenska University hospital

Gothenburg, Region Västra Götaland, Sweden

RECRUITING

Skaraborg hospital Skövde

Skövde, Region Västra Götaland, Sweden

RECRUITING

University hospital Örebro

Örebro, Region Örebro Län, Sweden

RECRUITING

Linköping University hospital

Linköping, Region Östergötland, Sweden

RECRUITING

Länssjukhuset Ryhov

Jönköping, Sweden

RECRUITING

Karlshamns sjukhus

Karlshamn, Sweden

RECRUITING

Karlstad Central hospital

Karlstad, Sweden

RECRUITING

Norrköpings sjukhus

Norrköping, Sweden

RECRUITING

Skellefteå hospital

Skellefteå, Sweden

NOT YET RECRUITING

Karolinska Universitetssjukhuset

Stockholm, 14186, Sweden

RECRUITING

Danderyd sjukhus AB

Stockholm, Sweden

RECRUITING

Akdemiska sjukhuset Uppsala

Uppsala, Sweden

RECRUITING

Varberg hospital

Varberg, Sweden

RECRUITING

Related Publications (1)

• Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.

  PMID: 38189593 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Atrial Fibrillation; Stroke; Cerebral Hemorrhage; Death; Venous Thrombosis

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Intracranial Hemorrhages; Hemorrhage; Thrombosis; Embolism and Thrombosis

Study Officials

• Marie Evans, Ass Prof

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

• Maria Svensson, Prof

  Uppsala University

  STUDY CHAIR

Central Study Contacts

Marie Evans, Ass Prof

CONTACT

+46760520852; marie.evans@regionstockholm.se

Caroline Moberg

CONTACT

caroline.moberg@ucr.uu.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Pragmatic Prospective Open Label Parallel-Group Multicenter Phase 3b Randomized Controlled Clinical Trial

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 10, 2023
• Study Start: February 17, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 4, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

NO (5); FI (3); SE (25); IC (1)