Efficacy of Low-Dose Apixaban Added to Standard Heparin Lock to Prevent Dysfunction of Tunneled Hemodialysis Catheters: A Randomized, PROBE, Parallel-Grupo Trial.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Clinically significant catheter dysfunction
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
盲法说明
This is a randomized, open-label, parallel-group trial. Participants and treating clinicians are aware of treatment allocation, as no placebo is used. To minimize assessment bias, all primary and secondary outcomes related to catheter dysfunction and catheter-related infections are adjudicated by an independent committee blinded to treatment allocation. Data provided to the adjudication committee are de-identified and coded to conceal group assignment. This approach is consistent with a PROBE (Prospective, Randomized, Open-label, Blinded Endpoint) study design
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: Heparin sodium lock solution (Drug)
Apixaban
Standard catheter care including intraluminal heparin lock per unit protocol, plus apixaban 2.5 mg orally every 12 hours, initiated after randomization (T0) 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.
干预措施: Apixaban (Drug)
Apixaban
Standard catheter care including intraluminal heparin lock per unit protocol, plus apixaban 2.5 mg orally every 12 hours, initiated after randomization (T0) 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.
干预措施: Heparin sodium lock solution (Drug)
结局指标
主要结局
Clinically significant catheter dysfunction
时间窗: From randomization (T0) up to 24 months
Time from randomization to the first clinically significant catheter dysfunction event, defined as either: (1) use of intraluminal thrombolytic therapy (alteplase/rt-PA), or (2) definitive catheter loss (permanent catheter removal or over-the-wire exchange) due to catheter dysfunction. The following are not considered events for the primary outcome: line reversal, flushing with crystalloid, postural changes, or radiography with subsequent manipulation unless they are followed by thrombolytic use or definitive catheter loss.
次要结局
- Major bleeding (ISTH)(Up to 24 months)
- Minor catheter dysfunction requiring simple maneuvers.(From randomization (T0) up to 24 months)
- Rescue procedures for catheter dysfunction (number of procedures per participant)(Up to 24 months)
- Catheter-related infection rate (per 1,000 catheter-days)(Up to 24 months)
- Clinically relevant non-major bleeding (ISTH)(Up to 24 months)
- All-cause mortality(Up to 24 months)
研究者
Juan Alberto Gomez Fregoso
Principal Investigator
Hospital Civil de Guadalajara