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

Официальное название

Efficacy of Low-Dose Apixaban Added to Standard Heparin Lock to Prevent Dysfunction of Tunneled Hemodialysis Catheters: A Randomized, PROBE, Parallel-Grupo Trial.

Обзор

This randomized, single-center, PROBE trial evaluates whether adding low-dose apixaban (2.5 mg orally every 12 hours) to standard intraluminal heparin lock prolongs primary functional patency of tunneled hemodialysis catheters compared with standard heparin lock alone. Adult patients on hemodialysis with a recently implanted, functioning tunneled catheter (≥8 days) will be randomized 1:1 and followed up to 24 months (or until catheter loss). Primary outcome is time to first intervention for catheter dysfunction or definitive catheter loss. Secondary outcomes include primary-assisted and secondary patency, thrombotic dysfunction, rescue procedures, catheter-related infection, bleeding (ISTH), and mortality. Outcomes adjudication will be blinded.

Подробное описание

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.

Вмешательства

• Препарат Apixaban
  Apixaban 2.5 mg orally every 12 hours, initiated after randomization (TO) and continued until administrative censoring at 24 months or earlier catheter loss/removal/exchange, modality change, kidney transplant, withdrawal, death, or end of study. Temporary interruptions, bleeding events, and adherence are recorded per protocol.
• Препарат Heparin sodium lock solution
  Heparin sodium catheter lock solution (1,000 IU/mL) instilled into each lumen of the tunneled hemodialysis catheter at the end of each dialysis session, using a volume equal to the catheter manufacturer's priming volume per lumen. The same lock protocol is used in both study arms.

Первичные конечные точки

• Clinically significant catheter dysfunction [Срок оценки: From randomization (T0) up to 24 months]

Вторичные конечные точки (6)

• Minor catheter dysfunction requiring simple maneuvers. [Срок оценки: From randomization (T0) up to 24 months]
• Rescue procedures for catheter dysfunction (number of procedures per participant) [Срок оценки: Up to 24 months]
• Catheter-related infection rate (per 1,000 catheter-days) [Срок оценки: Up to 24 months]
• Major bleeding (ISTH) [Срок оценки: Up to 24 months]
• Clinically relevant non-major bleeding (ISTH) [Срок оценки: Up to 24 months]
• All-cause mortality [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Мексика · 1 центр

• Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde" — Guadalajara

Идентификаторы

NCT: NCT07404345 · APICATH-HD-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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