Acute or Subacute Iliofemoral Vein Thrombosis: Aspiration for Flow Restoration Versus Standard Anticoagulation (IF-FLOW)

This is a prospective, multicenter, randomized controlled, superiority clinical trial. A total of 104 patients with acute or subacute iliofemoral deep vein thrombosis (DVT) are planned to be enrolled. Participants will receive either thrombus aspiration combined with standard anticoagulant therapy or standard anticoagulant monotherapy according to the randomization principle. The trial aims to verify the efficacy and safety of thrombus aspiration plus standard anticoagulant therapy versus standard anticoagulant therapy alone in the treatment of acute or subacute iliofemoral deep vein thrombosis.

Clinical follow-up assessments will be conducted at pre-discharge, 30 days, 6 months, 12 months, and 24 months after the procedure.

The hierarchical composite endpoint at 24 months post-procedure is defined as the primary efficacy endpoint.

Secondary efficacy endpoints include: immediate post-procedure thrombus clearance success rate (intervention group only), 30-day thrombus recurrence rate, Villalta score, VEINES-QOL/Sym quality of life questionnaire for venous insufficiency, and concomitant treatment (excluding treatment escalation).

Secondary safety endpoints include: major bleeding events within 30 days post-procedure, serious adverse events related to aspiration therapy and concomitant endovascular therapy, and serious adverse events other than major bleeding associated with anticoagulant therapy.

The trial is designed to evaluate the efficacy and safety of thrombus aspiration combined with standard anticoagulant therapy versus standard anticoagulant monotherapy for acute or subacute iliofemoral deep vein thrombosis.

Eligible subjects who meet the inclusion and exclusion criteria of the clinical trial will be randomly assigned (1:1) to either the intervention group (thrombus aspiration + standard anticoagulant therapy) or the control group (standard anticoagulant therapy). Physicians will conduct follow-up of subjects via outpatient visits, telephone interviews, and other means, with simultaneous efficacy and safety evaluations performed throughout the follow-up period.

of primary efficacy.

The hierarchical composite endpoint indicators are, in order: in-hospital death or treatment escalation, recurrent venous thrombosis of the target lesion or new-onset pulmonary embolism within 24 months, severity of the Villalta score at 24 months, and change in the VEINES score at 24 months. Monte Carlo simulation was used for sample size estimation. First, a fixed sample size was assumed, and 3,000 simulations were performed based on this sample size and the estimated parameters (see the table above). Statistical power was calculated as the proportion of rejecting the null hypothesis across the 3,000 simulations, and the assumed sample size was adjusted according to the obtained power.

Assuming the incidence of each hierarchical endpoint in the two groups is as shown in the table above, hypothesis testing was performed for superiority using a Z-test based on normal approximation. The simulation results indicate that with a one-sided α of 0.025, a total sample size of 88 patients (randomly assigned 1:1 to the experimental and control groups) provides approximately 85% statistical power to meet the requirement for superiority inference of the primary endpoint. Accounting for an approximately 15% dropout rate (5% due to withdrawal, loss to follow-up, or missed visits [excluding in-hospital death], and 10% due to missing Villalta and VEINES scores at 24 months), the final sample size is 104 patients.

Determination of Randomization Allocation Subjects were randomly assigned at a 1:1 ratio to the experimental group (thrombus aspiration combined with standard anticoagulant therapy) or the control group (standard anticoagulant therapy).

Stratified block randomization was adopted for group allocation in this trial, with stratification by participating study centers, and random allocation sequences were generated at a 1:1 ratio. After subjects signed the informed consent form, investigators at each sub-center completed randomization allocation via the randomization system.

Treatment Regimen

1. Treatment Allocation Investigators at each sub-center screened eligible subjects randomly in accordance with the above criteria. Subjects were allocated at a 1:1 ratio to either the experimental group or the control group.

   1.1 Experimental Group (Thrombus Aspiration Therapy) Subjects in the experimental group received thrombus aspiration therapy, and concomitant additional surgical procedures (e.g., catheter-based thrombus aspiration) were allowed based on clinical conditions. All subjects concurrently received standard anticoagulant pharmacotherapy.

   Thrombus Aspiration: Thrombus removal was performed only using thrombus aspiration catheters based on direct negative pressure principle. Combination with other mechanical thrombectomy devices/system principles is prohibited, including but not limited to: stent retrievers, pharmacomechanical thrombectomy (e.g., AngioJet catheter), mechanical thrombectomy devices (e.g., Aspirex). Thrombus aspiration was terminated when target vessels achieved complete recanalization with no residual thrombus (thrombus burden score = 0) as assessed by study physicians.

   If significant venous stenosis or occlusion remained after thrombus removal, balloon angioplasty and/or stent implantation were recommended for venous lesions with diameter stenosis ≥50% or lesions presenting obvious collateral circulation on angiography.

   Standard Anticoagulant Pharmacotherapy: All patients in the experimental group received a standard anticoagulant regimen. Coagulation parameters were monitored regularly during treatment to maintain anticoagulant effects within a safe therapeutic window.

   1.2 Control Group (Standard Anticoagulant Pharmacotherapy) Subjects in the control group received standard anticoagulant pharmacotherapy as the conventional treatment for acute or subacute iliofemoral deep vein thrombosis. Patients in the control group were not allowed to receive thrombus aspiration or any additional volume-reducing surgical interventions, and were managed with medication only.

   Standard Anticoagulant Pharmacotherapy: Control patients were administered standard anticoagulant therapy in accordance with clinical guidelines, including but not limited to low molecular weight heparin, warfarin, or direct oral anticoagulants (DOACs). Coagulation function, hepatic and renal function were closely monitored throughout treatment to ensure the safety of anticoagulation.

   Treatment Duration and Monitoring: Anticoagulant therapy was continued until the predefined study endpoint. Regular clinical examinations including hematological tests and imaging assessments were performed to evaluate therapeutic efficacy and safety profiles.

   1.3 Permitted Adjunct Endovascular Therapy Inferior Vena Cava (IVC) Filter: Physicians in both experimental and control groups could decide on IVC filter implantation and subsequent retrieval based on clinical judgment and individual patient conditions.

   Catheter-Directed Thrombolysis (CDT): For experimental patients receiving thrombus aspiration, intraoperative and postoperative catheter-directed thrombolysis was permitted to optimize thrombectomy efficacy, with a maximum treatment duration within 24 hours after the index procedure.

   Concomitant Additional Surgical Therapy: Experimental patients undergoing thrombus aspiration could receive other concomitant surgical interventions as clinically indicated. Following percutaneous catheter thrombus aspiration, balloon angioplasty and/or stent implantation were recommended for venous lesions with diameter stenosis ≥50% or obvious collateral circulation on angiography.

2. Treatment During Follow-up

A unified standard anticoagulant regimen was adopted for both the experimental group (thrombus aspiration plus standard anticoagulant therapy) and the control group (standard anticoagulant therapy) throughout the follow-up period. Direct oral anticoagulants are recommended as follows:

Rivaroxaban: Factor Xa inhibitor. Recommended dosage: 15 mg twice daily for 21 days, followed by a maintenance dose of 20 mg once daily.

Dabigatran: Direct thrombin inhibitor. Recommended dosage: 150 mg twice daily. The minimum duration of anticoagulant therapy was 3 months. For special populations, investigators could administer equivalent alternative anticoagulant regimens based on individual patient conditions and the above recommendations.

All implemented anticoagulant strategies, including the specified study regimen, guideline-equivalent alternative regimens, or clinically adjusted individualized anticoagulant schemes, shall be documented in detail in the Case Report Form (CRF).