A Phase 3 interventional study of Apixaban 2.5 milligram Oral Tablet in Chronic Kidney Diseases, Atrial Fibrillation and Stroke, sponsored by Region Stockholm. Recruiting at 34 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-04.
Sponsored by Region Stockholm · Phase 3, Interventional, and Treatment
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)
Background and rationale: Atrial fibrillation (AF) is common (15-30%) in patients with chronic kidney disease (CKD) and AF prevalence increases with severity of CKD. In late stages of CKD, randomized control trials (RCT) of both efficacy and safety of any anticoagulation therapy, both warfarin and direct oral anticoagulation (DOAC) drugs, for stroke prophylaxis in AF are lacking. The efficacy of warfarin and DOACs have been evaluated in observational trials in patients with stage 5 CKD, but the results have been conflicting, and these studies were all subjected to selection bias in one way or the other. Instead, observational studies have demonstrated several adverse side-effects. Among them an increased number of bleedings including hemorrhagic stroke in patients treated with warfarin, and calciphylaxis, a very serious complications unknown in the normal population linked to the withdrawal of vitamin-K-dependent protection of vascular calcification in CKD. With apixaban treatment several benefits were reported. Firstly, a potential protective effect against ischemic stroke. Secondly, a lower incidence of bleeding complications as observed in the major trials, and thirdly, no disturbance in vitamin K turnover as compared to warfarin treatment. In addition, apixaban treatment does not require routine monitoring and have fewer drug/food interactions. For patients with CKD stage 5, treatment with apixaban appears to have a lower bleeding risk than warfarin treatment.
Rationale to study design: There are no previous randomized controlled clinical trials in this study population. The SACK study is conducted in approximately 50 sites in Sweden, Finland, Norway, Iceland and Poland, and additional European countries, if necessary. In Sweden, the study will be register-randomized (via the national Swedish Renal Register [SNR]) whereas the other countries in the study will include patients in a traditional way for clinical trials.
The study design will be an individually randomized two-armed parallel-group design. Apixaban will be prescribed and renewed by the local investigator via regular prescription or distributed by the investigating site at regular intervals in all participating countries. Due to open-label prescription and safety reasons, the study will be conducted as an open-label trial with end-point evaluation. Patients who are randomized to apixaban and those who are randomized to standard of care with no anti-coagulation will receive all other guideline-recommended standard of care treatments. Patients already on prior warfarin or apixaban therapy, or on regular low molecular weight heparin (LMWH) can also be randomized to either treatment arm (their current anticoagulation is discontinued at the inclusion visit) after an individualized risk assessment. At inclusion, patients will provide routine blood samples including hemoglobin, eGFR, and coagulation parameters.
The end of the clinical study for each individual patient is defined as the End of Study (EoS) visit. The EoS for a patient is after 72 months or when 247 primary events have been reached, whichever comes first. An interim analysis will take place after 1000 patient-years with the purpose to evaluate event rate and to be able to closer determine the exact number of patients and duration of the trial. The end of the clinical trial is defined as the last visit of the last subject in the study (LVLS).
A Data and Safety Monitoring Board (DSMB) will supervise this study, and primary safety and efficacy endpoints and major bleedings will additionally be evaluated by independent external reviewers according to a predefined Central Event Adjudication charter.
Exploratory outcomes: Time to first thromboembolic event defined as a composite of deep vein thrombosis, pulmonary embolism, transient ischemic attack Time to dialysis access thrombosis Time to kidney replacement therapy Delayed graft function in patients undergoing kidney transplantation Thrombosis of renal artery or vein in patients undergoing kidney transplantation
Among the secondary safety outcomes are time to major bleeding according to ISTH criteria. We are especially interested in the safety outcomes of the subgroup undergoing a kidney transplantation from the waiting list and therefore we have an extended protocol for those participants.
3,090 studies on the registry are indexed under Renal Insufficiency, Chronic; 698 are open to participants now.
This study's planned enrollment of 1,400 is above the median of 73 across 2,157 interventional studies indexed under Renal Insufficiency, Chronic.
Browse Renal Insufficiency, Chronic studies →Region Stockholm is the lead sponsor of 121 studies on the registry; 69 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Participants may not be included in the study if any of the following criteria are met:
Any for anticoagulation including
Active bleeding or serious bleeding within 3 months, or
Planned for surgery
Being active on the kidney transplant waiting list is not an exclusion criterion if it is allowed according to the current clinical guidelines at the transplant clinic where the patient is registered. The patient must report changes in waiting list status to the investigator promptly.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Apixaban 2.5 mg twice daily (low dose) and all other standard of care
Drug: Apixaban 2.5 milligram Oral Tablet
All other Standard of care and no anticoagulation
Oral Tablet
Ischemic stroke or systemic embolism (efficacy)
Time to ischemic stroke or systemic embolism
Time frame: Up to 72 months
Intracranial bleeding (including hemorrhagic stroke) and fatal bleeding (safety)
Time to intracranial or fatal bleeding
Time frame: Up to 72 months
All-cause mortality
Time to death
Time frame: Up to 72 months
Cardiovascular event
Composite of time to myocardial infarction, cardiovascular intervention or cardiovascular death
Time frame: Up to 72 months
Individual components of cardiovascular event
Time to myocardial infarction and cardiovascular intervention and cardiovascular death
Time frame: Up to 72 months
Major bleeding
Time to major bleeding according to ISTH criteria (modified)
Time frame: Up to 72 months
Major bleeding in patients undergoing kidney transplantation
Time to major surgical bleeding according to ISTH criteria
Time frame: Up to 72 months
Thromboembolic event
Time to transitory ischemic attack, pulmonary embolism, deep vein thrombosis,
Time frame: Up to 72 months
Dialysis access thrombosis
Time to dialysis access thrombosis
Time frame: Up to 72 months
Kidney replacement therapy initiation
Time to Kidney replacement therapy initiation
Time frame: Up to 72 months
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Plan to share: No
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