Low-Dose Apixaban Added to Standard Heparin Lock Versus Heparin Lock Alone to Prevent Tunneled Hemodialysis Catheters Dysfunction (APICATH-HD)

Design: Single-center, randomized (1:1), parallel-group, superiority trial with a PROBE strategy (open-label clinical management; blinded outcome adjudication by an independent committee).

Arms / Interventions Arm 1: Control - Heparin Lock Alone

Intervention Name:

Heparin Lock

Description:

Intraluminal heparin lock after each hemodialysis session as standard care. Heparin concentration is 1,000 IU/mL, with per-lumen volume equal to the priming volume specified by the catheter manufacturer.

Arm 2: Intervention - Apixaban Plus Heparin Lock

Intervention Name:

Apixaban

Description:

Intraluminal heparin lock identical to the control arm (standard care; heparin 1,000 IU/mL with per-lumen volume according to device priming volume), plus systemic anticoagulation with apixaban 2.5 mg orally every 12 hours.

Population: Adults (≥18 years) on hemodialysis with a tunneled double-lumen catheter (Palindrome®) in the internal jugular (right/left) or femoral (right/left) position, functioning and ≥8 days post-implantation, without early dysfunction.

Procedures: Per dialysis session, record prescribed/achieved blood flow, inline pressures, alarms, recirculation, line inversion, and lock details; document formal interventions for dysfunction (rt-PA instillation, related angioplasty, over-the-wire exchange), and evaluate infections using CDC criteria.

Follow-up: Each dialysis session and monthly safety/adherence checks; administrative censoring at 24 months or upon catheter loss/replacement, refractory infection, switch to AV access, transplant, death, or end of study.

Safety: Bleeding surveillance (ISTH). Temporary interruption rules for procedures/bleeding/concomitant drugs. Independent DSMB with one interim analysis at ~50% of primary events using O'Brien-Fleming boundaries.

Inclusion criteria

• Age ≥18 years with end-stage kidney disease (CKD stage 5) receiving maintenance hemodialysis or initiating hemodialysis.
• Recently placed tunneled, double-lumen central venous hemodialysis catheter (tunneled CVC) in place for ≥8 days, with a post-placement radiograph confirming adequate tip position.
• Permitted catheter insertion sites: right internal jugular, left internal jugular, right femoral, or left femoral vein.
• Adequate initial catheter function, defined as ability to achieve the prescribed extracorporeal blood flow (suggested ≥300 mL/min) for ≥8 days after catheter placement.
• Conventional in-center hemodialysis schedule (2-3 sessions/week) at the study unit, with expected ability to complete follow-up for up to 24 months.
• Written informed consent provided.
• Willingness to receive only the protocol-assigned antithrombotic prophylaxis and to avoid non-study systemic anticoagulants or antiplatelet agents during the study period.

Exclusion criteria

• Non-tunneled hemodialysis catheter, subclavian catheter, or intracaval catheter placement not consistent with the protocol (e.g., catheter located in the SVC/IVC without a subcutaneous tunnel, or catheter location/site not permitted by the study).
• Tunneled catheter placed <8 days before randomization or radiographically confirmed catheter tip malposition at screening.
• Active bleeding; active peptic ulcer disease; or clinically significant gastrointestinal bleeding within the past 30 days; uncorrectable INR >1.5; platelet count <100,000/µL.
• High bleeding risk (HAS-BLED score >3) or major bleeding that is active or recent.
• Known coagulopathy; history of heparin-induced thrombocytopenia (HIT); or allergy/hypersensitivity to heparin, citrate, or rt-PA (alteplase).
• Severe hepatic impairment (e.g., Child-Pugh class C), clinically significant liver dysfunction that contraindicates DOAC therapy, or ongoing hemodialysis with regional citrate anticoagulation that cannot be modified per protocol.
• Active catheter exit-site infection or bloodstream infection/bacteremia at the time of randomization.
• Concomitant use of other systemic anticoagulants (e.g., warfarin, low-molecular-weight heparin, other DOACs) or high-intensity antiplatelet therapy (e.g., dual antiplatelet therapy).
• Pregnancy or breastfeeding.
• Women of childbearing potential who are unwilling to use a highly effective contraception method during the study and for 48 hours after the last dose of study medication.
• Life expectancy <6 months, current palliative/hospice care, or planned kidney transplant within ≤3 months.
• Concurrent participation in another clinical trial that could interfere with the study interventions or outcomes.
• Venography demonstrating significant venous stenosis involving the superior vena cava (SVC) or inferior vena cava (IVC).