Ultrasound to Enhance Paclitaxel Uptake in Critical Limb Ischemia: the PACUS Trial

Peripheral Arterial Disease, Angioplasty Clinical Trial

— PACUS  

Official title:

Use of Local Ultrasound to Enhance Local Paclitaxel Delivery Effect After Femoro-popliteal Percutaneous Transluminal Angioplasty in Patients With Critical Limb Ischemia: the PACUS Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02625740
• Other study ID #: Tor Vergata University
• Status: Completed
• Phase: N/A
• First received: November 30, 2015
• Last updated: December 8, 2015
• Start date: November 2013
• Est. completion date: November 2015

Study information

• Verified date: December 2015
• Source: University of Rome Tor Vergata
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial Summary

The PACUS Trial was a single center, single blinded, randomized trial designed to evaluate the safety and efficacy of intravascular percutaneous catheter-delivered ultrasound energy to improve local Paclitaxel delivery effects in critical limb ischemia patients due to femoral-popliteal artery disease.

Description:

Study design The PACUS Trial was a single center, single blinded, randomized trial designed to evaluate the safety and efficacy of intravascular percutaneous catheter-delivered high intensity, low-frequency ultrasound utilizing CardioProlific Genesis™ System to improve local paclitaxel delivery effect in patients with CLI due to femoral-popliteal calcific lesions and occlusions. The protocol was approved by a Local Review Boards and the Institutional Ethics Committee. All patients provided written informed consent before enrollment. The trial was conducted in accordance with the declaration of Helsinki.

Randomization Randomization occurred after successful crossing and pre-dilatation of the target lesion with a standard percutaneous angioplasty balloon without sub-intimal approach and/or flow limiting dissections. Patients were enrolled when a successful angiographic control was performed after PTA pre-dilatation. Subjects were randomly assigned by a computer-generated random sequence (2 blocks in a 1:1 ratio). Randomization was done in advance for all patients and without any stratification. The patients and physicians involved in the follow-up control were blinded to the treatment assignments through the completion of all 6 month follow-up evaluation. Operators were not blinded due to differences in treatment protocol. Twenty eight (28) patients were treated with an intravascular percutaneous catheter-delivered high intensity, low-frequency ultrasound and local Paclitaxel delivery with temporarily blood flow occlusion created by distal occlusion balloon (Study Group), and twenty eight (28) patients were treated with drug eluting balloon with conventional method (Control Group).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: November 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Rutherford category =4

• femoral-popliteal lesion =10cm

• successful intraluminal recanalization without need of a stent to obtain a satisfactory angiographic result

• at least one patent below the knee vessel

• patients older than 18 years

Exclusion Criteria:

• Rutherford category < 4

• pregnancy

• known allergies to study medications and materials

• need of sub-intimal approach to perform the recanalization

• target vessel stent release

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Arterial Disease, Angioplasty
• Peripheral Vascular Diseases

Intervention

Device:
• Local exposition of target lesion to high intensity, low-frequency ultrasound
Target lesion was exposed to 60 seconds of high intensity, low-frequency ultrasound generated by the Genesis™ system ( CardioProlific Inc., Hayward, CA). The ultrasound catheter is removed after the exposition.
• drug eluting ballon angioplasty
Target lesion was treated with an angioplasty, performed using the INPACT Admiral drug eluting ballon (Medtronic)
• Flow occlusion with an angioplasty balloon
Inflation of a 2 cm long balloon catheter Admiral (Medtronic) , located distally to the treatment area, in order to obtain a flow cessation

Drug:
• Local Paclitaxel infusion
Paclitaxel in a mixture with contrast medium at 1.0 µg/mm³ concentration was delivered to the treatment area for 60 seconds. The column of the Paclitaxel mixture filling the vessel was observed under the fluoroscopy and sustained during 60 seconds. The Paclitaxel /contrast medium mixture was then aspired with a 50 cc syringe and the distal balloon was deflated.

Procedure:
• Angiographic control
A final angiographic control was performed with injection of 10 cc of contrast medium and compared with the pre-procedural one.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Rome Tor Vergata

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with Freedom from clinically driven target lesion revascularization (TLR) and significant restenosis	Freedom from clinically driven target lesion revascularization (TLR) and significant restenosis as determined by digital subtraction angiography at 6 months follow-up	6 months follow up	No
Primary	Number of device and procedure related deaths and major adverse clinical events	Number of device and procedure related death and major adverse clinical events defined as stroke, myocardial infarction, need of surgical revascularization, distal embolization, recurrence of critical limb ischemia.	1 months follow-up	Yes
Secondary	Percentage of Intraoperative Technical success	Percentage of Technical success (Patients with technical success/Total population) was defined as successful recanalization of the target vessel with =30% residual stenosis after the procedure	Intraoperative	No
Secondary	Number of participants with Clinically driven target lesion revascularization	Number of participants with Target lesion revascularization, defined as any repeat surgical or percutaneous interventions of the target lesion due to loss of patency as evaluated by DSA	12 months follow up	No
Secondary	Number of participants with clinical improvement	Number of participants with Clinical improvement, defined as freedom from target limb amputation, target vessel revascularization, and increase in Rutherford class.	12 months follow up	No
Secondary	Number of Death and major adverse clinical events	Number of death and major adverse clinical events included stroke, myocardial infarction, need of surgical revascularization, distal embolization, recurrence of critical limb ischemia.	12 months follow up	Yes