Chronic Limb IschemiaPhase 2LIMBO-PTANCT02479555
Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
A Phase 2 study testing Dexamethasone sodium phosphate injection, USP, 4 mg/mL in people with Chronic Limb Ischemia, run by Mercator MedSystems, Inc. at 3 sites in Germany.
Trial summary
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Limb Ischemia
- What is being tested?
- Dexamethasone sodium phosphate injection, USP, 4 mg/mL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesGermany
- Study dates
- Jan 2016to Aug 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Screening Criteria:
- Age ≥18 years
- Patient or patient's legal representative have been informed of the nature of the study, agrees to participate and has signed an IRB/EC approved consent form
- Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation
- Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 4, 5 or 6
- Life expectancy >1 year in the Investigator's opinion
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- Angiographic Criteria:
- Successful revascularization of the TL with less than 30% residual stenosis, run-off down to the foot and direct in-line flow to any foot wound
- Reference vessel(s) diameter ≥2 mm
- Single or multiple atherosclerotic lesion ≥70% in at least one infrapopliteal crural target vessel including the tibioperoneal trunk that totals up to 30 cm in length (with no greater than 5 cm length of contiguous intervening normal artery), with possible extension into the popliteal artery distal to the center of the knee joint space (the P3 segment)
Who cannot join
- Screening Criteria:
- Patient unwilling or unlikely to comply with visit schedule
- Planned major index limb amputation
- Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
- Inability to receive study medications
- Estimated glomerular filtration rate (eGFR) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis
Show all 18Show fewer
- Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature
- Angiographic/Procedural Criteria:
- Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries in which there is a failure to successfully treat and obtain a <30% residual stenosis
- Index lesion length is >30 cm as measured from proximal normal vessel to distal normal vessel
- Total length of lesions treated during the case (including target lesion, inflow lesions, and other non-index lesions) >50 cm
- Lesions revascularized during the index case but untreated by Bullfrog
- Use of alternative therapy, e.g. atherectomy, laser, or radiation therapy, as part of the index lesion treatment, or use of any drug eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) for treatment of any infra-inguinal lesions during the study procedure or during the initial six-month follow up period
- Previously implanted stent in the TL(s)
- Aneurysm in the target vessel
- Acute thrombus in the target limb
- Failure to cross the TL with a guide wire; however, subintimal wire crossing is allowed
- Heavy eccentric or concentric calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall
Trial locations and contacts
3 sites in 1 country.
Germany3 sites, 3 recruiting
- Recruiting
Universitäts-Herzzentrum Freiburg Bad Krozingen GmbH
Bad Krozingen, 79189
Thomas Zeller, MD
- Recruiting
Universitätsklinikum Leipzig AöR
Leipzig, 04103
Dierk Scheinert, MD
- Recruiting
Medinos Kliniken des Landkreiss Sonneberg GmbH
Sonneberg, 96515
Marcus Thieme, MD
About this study
Official title: LIMBO-PTA: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).
Read the detailed description
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone sodium phosphate injection (4 mg/mL) after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 120 patients (60 treatment and 60 control), including up to 20 Rutherford 6 patients (10 treatment and 10 control) at up to 30 sites in Europe and the United States. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of dexamethasone in reducing inflammation and restenosis in patients with clinical evidence of chronic critical limb ischemia with an angiographically significant lesion in the infrapopliteal crural vessels.
- Conditions
- Chronic Limb Ischemia
- Being tested
- Dexamethasone sodium phosphate injection, USP, 4 mg/mL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone sodium phosphate injection, USP, 4 mg/mLDrug
Post-balloon angioplasty revascularization, the unblinded Pharmacist will prepare a sterile 20 mL syringe (Luer locking) with 16 mL of investigational drug or placebo per assignment. The unblinded Pharmacist provides syringe to investigator. Syringe shall only be labeled with the study number, patient number, randomization number and "Investigational Drug".
"Investigational Drug" will be administered via Bullfrog Micro-Infusion Device.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group: Dexamethasone Delivery | Active comparator | Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States.
Patients will be randomized 1:1 to receive either the active treatment or control therapy.
Treatment Group: Standard endovascular revascularization therapy consisting of angioplasty followed by Dexamethasondihydrogenphosphat-dinatrium (Ph.Eur.) 4 mg/mL Injektionslösung and with or without stent placement. The drug is diluted to 3.2 mg/mL and administered to the adventitia per Bullfrog Instructions for Use in a dose of 0.8 mg dexamethasone (0.25 mL) per cm of desired vessel treatment length, up to 30 cm. Receives: Drug: Dexamethasone sodium phosphate injection, USP, 4 mg/mL |
| Control Group | No intervention | Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States. Patients will be randomized 1:1 to receive either the active treatment or control therapy. Control Group: Standard endovascular revascularization therapy consisting of angioplasty with or without stent placement. No specific distribution of gender regarding enrollment or randomization is intended. There will also be a separate randomization of patients with Rutherford 6 score to a maximum of 20 enrolled patients. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Freedom from MALE
Freedom from major adverse limb event (MALE) within 6 months.
Measured: Up to 6 months following the procedure
Freedom from CD-TLR
Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.
Measured: Up to 6 months following the procedure
Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.
Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.
Measured: Up to 6 months following the procedure
TVAL% change from post-procedure
Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any CD-TLR of the target lesion before 6 months.
Measured: 6 months following the procedure
Secondary outcomes (19)
Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.
Freedom from composite of death, unplanned amputation and CD-TLR, serious adverse events (SAE) and MALE.
Measured: Up to 12 months following the procedure
Event-free survival
Proportion of patients reaching 12-month endpoint without a composite clinical safety event.
Measured: 12 months following the procedure
QVA change from post-procedure
Improvement in % diameter stenosis (%DSS) of the target lesion (TL) and the maximum late lumen loss for the lesion (LLL) will be assessed by quantitative vascular angiography (QVA).
Measured: 6 months following the procedure
IVUS change from post-procedure
Improvement in intravascular ultrasound (IVUS) result with in the TL (subgroup analysis).
Measured: 6 months following the procedure
Amputation-free survival
Percentage of patients reaching the endpoints without major or minor amputation.
Measured: 30 days, 6 and 12 months post-procedure
Major and minor amputations and amputation level
Percentage of patients requiring amputation (major: above ankle, minor: below ankle), categorized by level on the foot, ankle, or leg.
Measured: 30 days, 6 and 12 months post-procedure
Change in foot wounds versus baseline
The number and total size of foot wounds, reduction in number and size of baseline wounds, and occurrence of new wounds (number and size) will be measured against baseline.
Measured: 30 days, 6 and 12 months post-procedure
Resolved CLI death
The rate of deaths in patients who had a resolution of their critical limb ischemia (CLI).
Measured: 30 days, 6 and 12 months post-procedure
CD-TLR
Measured: 30 days, 6 and 12 months post-procedure
Primary sustained clinical improvement versus baseline
Sustained upward shift of at least 1 category on Rutherford classification as compared to baseline without the need for repeated TLR or surgical revascularization in amputation-free surviving subjects.
Measured: 30 days, 6 and 12 months post-procedure
Secondary sustained clinical improvement versus baseline
Sustained upward shift of at least 1 category on Rutherford classification as compared to baseline including the need for repeated TLR or surgical revascularization in amputation-free surviving subjects.
Measured: 30 days, 6 and 12 months post-procedure
SVS WIfI score versus baseline
Measured: 30 days, 6 and 12 months post-procedure
EQ5D versus baseline
Quality of life assessment.
Measured: 30 days, 6 and 12 months post-procedure
Walking capacity assessment versus baseline
Measured: 30 days, 6 and 12 months post-procedure
SAE/MALE assessment
Measured: 30 days, 6 and 12 months post-procedure
Inflammatory biomarker changes from baseline
Measured: 24 hours and 30 days
Healthcare economic analysis
An analysis of the economics associated with the care of patients, including number of hospital days throughout the study, return visits and hospitalizations, time from index procedure to required revascularization and number of index-lesion-related readmissions.
Measured: From baseline to 24 months
Infusion technical success
The grade of distribution (A-F) around infusion sites will be used as a qualitative measure of technical success of adventitial delivery of the drug.
Measured: Intra-procedural
Revascularization success
Establishment of antegrade flow with residual stenosis <30% by angiogram.
Measured: Intra-procedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2015 (estimated)
- Study startJan 2016
- Primary completionAug 2020 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Limb IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mercator MedSystems, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dierk Scheinert, MD, Principal investigator, University Hospital of Leipzig
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02479555
- Sponsor's protocol ID
- CIP0169
- Acronym
- LIMBO-PTA
- Status last verified
- Feb 2020
- First submitted
- 15 Jun 2015
- Last updated
- 20 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LIMBO-PTA: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
- ClinicalTrials.gov ID
- NCT02479555
- Acronym / sponsor ID
- LIMBO-PTA / CIP0169
- Conditions
- Chronic Limb Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Mercator MedSystems, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2016 (actual)
- Primary completion
- Aug 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 24 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).
Detailed description
This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone sodium phosphate injection (4 mg/mL) after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 120 patients (60 treatment and 60 control), including up to 20 Rutherford 6 patients (10 treatment and 10 control) at up to 30 sites in Europe and the United States. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of dexamethasone in reducing inflammation and restenosis in patients with clinical evidence of chronic critical limb ischemia with an angiographically significant lesion in the infrapopliteal crural vessels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group: Dexamethasone Delivery | Active comparator | Drug: Dexamethasone sodium phosphate injection, USP, 4 mg/mLUp to 60 angioplasty procedures at up to 30 sites in Europe and in the United States. Patients will be randomized 1:1 to receive either the active treatment or control therapy. Treatment Group: Standard endovascular revascularization therapy consisting of angioplasty followed by Dexamethasondihydrogenphosphat-dinatrium (Ph.Eur.) 4 mg/mL Injektionslösung and with or without stent placement. The drug is diluted to 3.2 mg/mL and administered to the adventitia per Bullfrog Instructions for Use in a dose of 0.8 mg dexamethasone (0.25 mL) per cm of desired vessel treatment length, up to 30 cm. |
| Control Group | No intervention | –Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States. Patients will be randomized 1:1 to receive either the active treatment or control therapy. Control Group: Standard endovascular revascularization therapy consisting of angioplasty with or without stent placement. No specific distribution of gender regarding enrollment or randomization is intended. There will also be a separate randomization of patients with Rutherford 6 score to a maximum of 20 enrolled patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥18 years
- Patient or patient's legal representative have been informed of the nature of the study, agrees to participate and has signed an IRB/EC approved consent form
- Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation
- Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 4, 5 or 6
- Life expectancy >1 year in the Investigator's opinion
Key exclusion criteria (18 listed)
- Patient unwilling or unlikely to comply with visit schedule
- Planned major index limb amputation
- Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
- Inability to receive study medications
- Estimated glomerular filtration rate (eGFR) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexamethasone sodium phosphate injection, USP, 4 mg/mLPost-balloon angioplasty revascularization, the unblinded Pharmacist will prepare a sterile 20 mL syringe (Luer locking) with 16 mL of investigational drug or placebo per assignment. The unblinded Pharmacist provides syringe to investigator. Syringe shall only be labeled with the study number, patient number, randomization number and "Investigational Drug". "Investigational Drug" will be administered via Bullfrog Micro-Infusion Device. | Drug | Treatment Group: Dexamethasone Delivery |
Primary outcome
Freedom from MALE
Time frame: Up to 6 months following the procedure
Freedom from major adverse limb event (MALE) within 6 months.
Freedom from CD-TLR
Time frame: Up to 6 months following the procedure
Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.
Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.
Time frame: Up to 6 months following the procedure
Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.
TVAL% change from post-procedure
Time frame: 6 months following the procedure
Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any CD-TLR of the target lesion before 6 months.
19 secondary outcomes
Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.
Time frame: Up to 12 months following the procedure
Event-free survival
Time frame: 12 months following the procedure
QVA change from post-procedure
Time frame: 6 months following the procedure
IVUS change from post-procedure
Time frame: 6 months following the procedure
Amputation-free survival
Time frame: 30 days, 6 and 12 months post-procedure
Major and minor amputations and amputation level
Time frame: 30 days, 6 and 12 months post-procedure
Change in foot wounds versus baseline
Time frame: 30 days, 6 and 12 months post-procedure
Resolved CLI death
Time frame: 30 days, 6 and 12 months post-procedure
CD-TLR
Time frame: 30 days, 6 and 12 months post-procedure
Primary sustained clinical improvement versus baseline
Time frame: 30 days, 6 and 12 months post-procedure
Secondary sustained clinical improvement versus baseline
Time frame: 30 days, 6 and 12 months post-procedure
SVS WIfI score versus baseline
Time frame: 30 days, 6 and 12 months post-procedure
EQ5D versus baseline
Time frame: 30 days, 6 and 12 months post-procedure
Walking capacity assessment versus baseline
Time frame: 30 days, 6 and 12 months post-procedure
SAE/MALE assessment
Time frame: 30 days, 6 and 12 months post-procedure
Inflammatory biomarker changes from baseline
Time frame: 24 hours and 30 days
Healthcare economic analysis
Time frame: From baseline to 24 months
Infusion technical success
Time frame: Intra-procedural
Revascularization success
Time frame: Intra-procedural
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dierk Scheinert, MD principal investigator
University Hospital of Leipzig
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexamethasone sodium phosphate injection, USP, 4 mg/mL in people with Chronic Limb Ischemia, run by Mercator MedSystems, Inc. at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kristen L. Poole, PhD (510-564-7761 ext. 818, kpoole@mercatormed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Freedom from MALE (time frame: Up to 6 months following the procedure). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020.