Effect of the Amplifi™ Vein Dilation System on Outflow Vein Dilation and AV Fistula Maturation (AMPLIFI-1)

A Pivotal Study to Evaluate the Effect of the Amplifi™ Vein Dilation System on Outflow Vein Dilation and Arteriovenous Fistula Maturation

The AMPLIFI-1 Study is a prospective, multicenter pivotal clinical trial designed to evaluate the safety and effectiveness of the Amplifi™ Vein Dilation System in patients requiring distal arteriovenous fistula (AVF) creation for hemodialysis. The study has two cohorts: a randomized controlled (RC) cohort of patients with suitable cephalic veins (≥2.5 mm) randomized 2:1 to Amplifi treatment plus AVF creation versus standard AVF creation alone, and a non-randomized small vein cohort (NRC) of patients with borderline veins (1.7 to <2.5 mm) treated with Amplifi therapy followed by AVF creation.

AMPLIFI-1 is a staged, multicenter clinical investigation evaluating the safety and effectiveness of the Amplifi™ Vein Dilation System in patients with end-stage renal disease (ESRD) undergoing distal arteriovenous fistula (AVF) creation. The system provides controlled, continuous extracorporeal blood flow to the cephalic vein over 24 to 72 hours, inducing flow-mediated dilation prior to surgery.

The study includes two cohorts based on baseline cephalic vein diameter:

Randomized Controlled (RC) Cohort: Subjects with vein diameter ≥2.5 mm are randomized 2:1 to receive either Amplifi therapy followed by AVF creation or AVF creation alone. This cohort supports the primary effectiveness endpoint and provides the control group reference.

Non-Randomized Cohort (NRC): Subjects with borderline cephalic veins (1.7 mm to <2.5 mm) are treated with Amplifi therapy followed by AVF creation. Effectiveness is evaluated against a performance goal informed by the RC control group and external benchmarks.

The primary endpoint is physiologic AVF maturation at 2 weeks post-creation, defined as brachial artery flow ≥500 mL/min and outflow vein diameter ≥5 mm on duplex ultrasound. Secondary endpoints include functional maturation, AVF patency, and early safety events.

The study uses a staged approach beginning with a 5-subject initial safety cohort. All procedures follow a standardized AVF surgical and imaging protocol. The trial includes centralized core lab review of imaging and adverse event adjudication. Data from both cohorts will be analyzed separately and pooled to support a proposed indication spanning the studied vein size range.

Inclusion Criteria:

1. Age ≥ 18 years

2. Indicated for wrist or distal forearm radiocephalic AVF creation based on Investigator's standard practice

3. End-Stage Renal Disease (ESRD) receiving maintenance hemodialysis.

4. Baseline cephalic vein diameter between >1.7 mm and <3.2 mm at the proposed Study AVF creation site in the distal forearm, with a continuous distal segment or tributary suitable for Amplifi System Outflow Catheter placement, including:

   • A forearm cephalic vein segment of ≥ 14 cm in length that provides an approximately 10 cm cannulation zone, free of detectable occlusions or stenosis, with collaterals.

   • Central continuity of the forearm cephalic vein at the elbow demonstrated through one or any combination of the following pathways:

     1. the upper arm cephalic vein,
     2. the median cubital vein connecting to the upper arm basilic vein,
     3. the perforator vein connecting to the deep venous system.

   • Upper arm veins must show central continuity with no detectable occlusions.

5. Palpable radial artery with a diameter of ≥ 2.0 mm at the site of proposed AVF creation without significant stenosis along the course

6. Positive Allen's Test

7. At least one patent internal jugular vein suitable for Amplifi Inflow Catheter insertion

8. Subject has voluntarily signed written informed consent

Exclusion Criteria:

1. Known allergy to Amplifi System components (polyurethane, nitinol), iodinated contrast agents, heparin, or apixaban
2. Known or suspected active infection at the proposed time of Amplifi System placement
3. Known bleeding diathesis, including from uncorrected coagulopathy
4. Known thrombophilia, requiring treatment
5. Hb <7 gm/dL
6. Platelet level < 100,000 /mm3
7. Significant radial artery calcification
8. Need for continued treatment with anti-platelet agents or other anticoagulants (other than apixaban) during the Amplifi System treatment period
9. Known history of patent foramen ovale > 2 mm
10. History of recent intracranial or gastrointestinal bleeding
11. Documented recent central venous or right atrial thrombus
12. Known presence or recent history of intracranial or gastrointestinal bleeding or presence of underlying conditions that would predispose to intracranial or internal bleeding. Documented recent central venous or right atrial thrombus
13. History of recent ipsilateral central venous occlusion, stenosis > 50%, angioplasty, or stent placement
14. Pregnancy, lactation, or plans to become pregnant during the Study
15. Expected survival less than 12 months
16. Unwillingness or inability to comply with procedures specified in the Protocol, or difficulty or inability to return for follow-up visits as specified by the Protocol
17. Participation in any other investigational drug or medical device study that has not completed primary endpoint evaluation or clinically interferes with the endpoints from the Study, or planned future participation in such studies prior to the completion of the Study