Sack

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital, Medical University Of Silesia Katowice Poland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

7 Feb 2023 → ongoing

Decision date (initial)

2022-11-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Swedish Research Council (Vetenskapsrådet)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Our main objective is to study the efficacy and safety of apixaban as stroke prophylaxis in patients with CKD stage 5 and AF with or without dialysis treatment. Our study hypothesis is that compared to no anticoagulation, apixaban reduces the incidence of ischemic stroke and systemic embolism without causing an unacceptable increase in fatal or intracranial bleedings.

The primary efficacy objective is to evaluate if treatment with apixaban and standard of care compared to standard of care without anticoagulation decreases the risk of ischemic stroke and systemic embolism (composite) in people with CKD stage 5 and AF (with or without dialysis).

Secondary objectives 6

1. To evaluate if treatment with apixaban and standard of care cause an unacceptable increase in the risk of fatal bleeding and intracranial bleeding (including hemorrhagic stroke) compared to standard of care without anticoagulation in people with CKD stage 5 and AF (with or without dialysis)
2. To evaluate the risk of cardiovascular events in people with CKD stage 5 and AF (with or without dialysis treatment) treated with apixaban compared to standard of care without anticoagulation.
3. To evaluate the risk of all-cause mortality in people with CKD stage 5 and AF (with or without dialysis treatment) treated with apixaban compared to standard of care without anticoagulation.
4. To evaluate the risk of all-cause stroke in people with CKD stage 5 and AF (with or without dialysis treatment) treated with apixaban compared to standard of care without anticoagulation.
5. To evaluate the risk of major bleedings in people with CKD stage 5 and AF (with or without dialysis) treated with apixaban compared to standard of care without anticoagulation
6. To evaluate the risk of thrombosis in people with CKD stage 5 and AF (with or without dialysis) treated with apixaban compared to standard of care without anticoagulation

Conditions and MedDRA coding

Atrial fibrillation and Chronic Kidney Disease stage 5

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed Written informed consent (on paper or digital)
2. Men or women ≥18 years
3. 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).
4. Diagnosis of paroxysmal, persistent, or permanent atrial fibrillation (AF) or atrial flutter (AFL).
5. CHA2DS2-VASc score ≥2 for men or ≥3 or more for women as an indication for oral anticoagulation.
6. Women of childbearing potential (WOCBP) should have a negative highly sensitive pregnancy test at screening and must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug.

Exclusion criteria 8

1. AF or AFL due to reversible causes (e.g., thyrotoxicosis, pericarditis).
2. Any degree of rheumatic mitral stenosis or moderate-to-severe non-rheumatic mitral stenosis at the time of inclusion into the study.
3. Any condition other than AF or AFL that requires chronic anticoagulation (e.g., a prosthetic mechanical heart valve, antiphospholipid syndrome).
4. Any contraindication for anticoagulation including a) endocarditis, b) documented intolerance for apixaban, c) liver disease with documented coagulation disorder, d) pregnancy or breast feeding.
5. Active bleeding or serious bleeding within 3 months, or a) documented hemorrhagic blood dyscrasia or a very high bleeding risk according to investigator, b) patients currently receiving dual antiplatelet therapy.
6. Planned for surgery a) kidney transplantation with a living donor within 3 months, b) active on the kidney transplant waiting list at a kidney transplant center where apixaban use is prohibited, c) valvular heart disease surgery
7. Current use of strong inhibitors of both CYP3A4 and P-glycoprotein in accordance with the SmPC of apixaban (2,5 mg) or regular intake of NSAID or COX2 inhibitors.
8. Any condition or circumstance in which the patient should not participate in the study according to the study investigator (reason documented in the pre-screening protocol).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Ischemic stroke and systemic embolism (composite)

Secondary endpoints 5

1. Composite event of intracranial bleeding (including hemorrhagic stroke) and fatal bleeding
2. Hospitalization for myocardial infarction, cardiovascular intervention, or cardiovascular death (composite)
3. All-cause death
4. All-cause stroke or systemic embolism
5. Major bleeding (as defined in the International Society on Thrombosis and Haemostasias (ISTH) consensus)

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Halsovagen, Flemingsberg Flemingsberg

City

Huddinge

Postcode

141 86

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Marie Evans

Public contact point

Organisation

Karolinska University Hospital

Contact name

Marie Evans

Medical University Of Silesia Katowice Poland

Sponsor organisation

Medical University Of Silesia Katowice Poland

Address

Ul. Ksiecia Jozefa Poniatowskiego 15

City

Katowice

Postcode

40-055

Country

Poland

Sponsor responsibilities

Article 77 compliance

Karolinska University Hospital

Contact point sponsor

Karolinska University Hospital

Article 77 implementation

Karolinska University Hospital

Locations

7 EU/EEA countries · 66 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 36 files

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

Application history

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