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

December 8, 2015 updated by: Roberto Gandini, University of Rome Tor Vergata

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Study group
After crossing the lesion with a guidewire, patients will be treated with intravascular high intensity, low-frequency ultrasound followed by local administration of liquid mixture of Paclitaxel and Iopromide-370 with predetermined dosage of 1.0 µg/mm
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.
Device: 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.
Active Comparator: Control group
After crossing the lesion with a guidewire, patients will be treated with drug eluting ballon angioplasty with the In.Pact Admiral ballon (Medtronic)
Procedure: Angiographic control
A final angiographic control was performed with injection of 10 cc of contrast medium and compared with the pre-procedural one.
Device: drug eluting ballon angioplasty
Target lesion was treated with an angioplasty, performed using the INPACT Admiral drug eluting ballon (Medtronic)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of patients with Freedom from clinically driven target lesion revascularization (TLR) and significant restenosis
Time Frame: 6 months follow up
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
Number of device and procedure related deaths and major adverse clinical events
Time Frame: 1 months follow-up
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Intraoperative Technical success
Time Frame: Intraoperative
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
Number of participants with Clinically driven target lesion revascularization
Time Frame: 12 months follow up
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
Number of participants with clinical improvement
Time Frame: 12 months follow up
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
Number of Death and major adverse clinical events
Time Frame: 12 months follow up
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Rome Tor Vergata

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Tor Vergata University

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings