Plain English Summary
Background and study aims
Peripheral arterial disease (PAD) is a common condition in which the blood flow to the legs is restricted. This happens because of the buildup of a fatty substance (plaque) on the walls of arteries. Over time this can cause the main arteries in the legs to become narrowed (stenosed) or blocked (occluded). As the arteries become narrower, patients begin the feel pain even when at rest and are at severe risk of developing ulcers or gangrene (acute lower limb ischaemia), which in severe cases can lead to amputation. Many patients are treated with blood thinning medication or surgery to restore blood flow to the leg (revascularisation), however these treatments are not always successful. Today, the most popular and frequently used treatments are surgery and/or thrombolysis. Thrombolysis is a treatment which involves breaking down blood clots which may be blocking the arteries using a type of medication called thrombolytics. They are administered through catheter (tube) inserted into the major artery in the groin. Both therapies are associated with high death rate and serious complications. Catheter therapy itself is less invasive than surgical treatment and therefore, different catheters have been developed that can break up the clot mechanically (mechanical debulking). However, mechanical removal has not replaced the traditional treatment so far, mainly due to limited experience with the new techniques as well as low efficacy of those approaches alone which often requires a combination with thrombolysis. The aim of this study is to find out whether mechanical debulking can be successfully and safely used without having to use thrombolysis and/or open surgery.
Who can participate?
Adults with symptomatic acute lower limb ischaemia.
What does the study involve?
All participants undergo treatment using the mechanical debulking method. This involves a catheter (thin, flexible tube) being inserted into the main artery in the affected leg via the groin and used to mechanically break down the blood clot. Participants are monitored closely for any complications until they are discharged from hospital. In addition, they undergo blood vessel scans to see if the arteries have become successfully unblocked at discharge and after 30 days and 12 months. In addition, the number of patients who require further treatment, such as amputation or thrombolysis, are recorded for one year.
What are the possible benefits and risks of participating?
Participants may benefit from a better chance of survival and lower complication rate. In addition, patients who are unable to have traditional treatment for medical reasons benefit from being able to receive treatment. There is a small risk of a blockage to blood flow or blood vessel perforation (piercing).
Where is the study run from?
University Hospital and 3rd Medical Faculty of Charles University (Czech Republic)
When is the study starting and how long is it expected to run for?
January 2009 to December 2016
Who is funding the study?
Investigator initiated and funded (Czech Republic)
Who is the main contact?
Professor Miroslav Bulvas
miroslav.bulvas@fnkv.cz
Trial website
Contact information
Type
Scientific
Primary contact
Prof Miroslav Bulvas
ORCID ID
http://orcid.org/0000-0003-4211-6696
Contact details
Dept. Med. 3
University Hospital Kralovske Vinohrady
Srobarova 50
Prague
100 34
Czech Republic
+420 267163791
miroslav.bulvas@fnkv.cz
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Prospective, single-arm and non-sponsored trial to evaluate potential of selected mechanical debulking techniques to eliminate thrombolysis and/or open surgery from initial therapy of acute and subacute ischaemia of lower limbs
Acronym
Study hypothesis
The aim of this study is to establish whether the initial treatment of patients with acute and subacute lower limb ischaemia can be done successfully and safely by mechanical debulking of target vessels with a catheter combining thrombectomy and atherectomy, without having to use catheter-directed thrombolysis and/or open surgery.
Ethics approval
Ethics Board of University Hospital Kralovske Vinohrady and Charles University 3rd Medical School, 01/04/2009, ref: EK /IV-2/2009
Study design
Prospective single-arm single-centre non randomised study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
See additional files
Condition
Acute and subacute ischeamia of lower limbs
Intervention
After recruitment, all patients undergo digital subtraction angiography and endovascular treatment. The procedure starts with local anesthesia of the groin tissue and insertion of percutaneous sheath. Significant stenosis proximal to target occlusion is dilated before mechanical debulking to allow sufficient inflow to Rotarex head during its action. Endovascular therapy is based on target vessel mechanical debulking with the Rotarex catheter. Intraluminal passage of guide wire through occlusion is a condition for usage of the technique together with the vessel diameter of 4 mm or more. Control angiography is performed after Rotarex passage. Running (activation) time and number of catheter passages are documented. Percutaneous aspiration thromboembolectomy (PAT) or clot extraction with endomyocardial biopsy device are performed to remove residual clot, if necessary. Percutaneous transluminal angioplasty (PTA) or stenting are used as adjunctive techniques to treat underlying residual stenoses and/or vessel wall irregularities, if angiographically relevant. Additional significant infrapopliteal lesions (acute, subacute or chronic) are managed by PAT, PTA and/or stenting. Catheter-directed thrombolysis and/or open surgical revascularization are immediately considered in patients where mechanical treatment is not successful. Number of patent calf vessels is registered before and after treatment. After the intervention, low molecular weight heparin or unfractioned heparin is administered subcutaneously in preventive doses for 24 hours. Clopidogrel is administered orally in a dose of 75 mg/24 hours for next three months and Oral administration of acetylsalicylic acid (100mg/24 hours) is started after three months and maintained for life. Long-term oral anticoagulation with warfarin is started, if necessary. Individual antithrombotic measures are adopted in selected cases.
Major and minor complications are monitored. After discharge, the patients are followed on ambulantory basis including duplex sonography and ankle-brachial index measurements.
The criteria for reintervention during follow-up are based on clinical symptoms (clinically driven intervention). Repeat percutaneous or surgical interventions are planned only in case of the presence of rest pain, ischaemic lesions (primary ulcer or nonhealing ulcer), or disabling intermittent claudication, while partial or complete reocclusions of previously treated arterial segment which do not present with these symptoms are managed conservatively.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measure
1. Number of thrombolytic and surgical revascularization procedures, deaths and amputations is registered at discharge, 30 days and 12 months
2. Amputation-free survival (percentage of patients who survived with both limbs) is evaluated at 30 days and 12 months
Secondary outcome measures
1. Clinical success is defined as technical success of the procedure and relief of acute ischemic symptoms at discharge and at 30 days
2. Overall clinical success is defined as relief of acute ischemic symptoms and the patient´s return to at least his/her pre-occlusive clinical baseline level after the therapy - including adjunctive therapeutic procedures
3. Technical success is defined as restoration of antegrade flow and residual diameter stenosis of 30% or less
4. Hemodynamic success is defined by increase of ABI (ankle-brachial index) for more than 0.10 after the intervention. It reflects overall effect of all recanalization techniques used. ABI is established by doppler as a dimensionless ratio of distal systolic blood pressure and arm systolic blood pressure
5. Primary patency refers to continued flow through treated target vessel without intervention at given time interval (30 days, 12 months), established on the basis of symptoms, physical examination, ultrasound examination or angiography
6. Secondary patency refers to continued flow through treated target vessel that was restored after reocclusion (durability of second intervention).
7. Number of infrapopliteal interventions is registered immediately after the intervention on angiography
8. Difference in observed parameters between thrombotic and embolic subgroups is assessed by statistical evaluation.
9. Difference in observed parameters between patients with acute and subacute ischaemia is assessed by statistical evaluation
10. Adverse events are registered during intervention, at 30 days and 12 months
10.1. Hemorrhagic and nonhemorrhagic complications are monitored and recorded in patient´s hospital documentation, hospital database, intervention protocol, hospital ambulatory care database and database of laboratory examinations
10.2. Major bleeding is defined as an intracranial bleed, bleeding resulting in death, or bleeding requiring transfusion, surgery, or cessation of endovascular treatment
10.3. Minor bleeding is defined as less severe bleeding managed by local compression, increases in vascular sheath size, or decreases in dose of the lytic, anticoagulant, or antiplatelet drug
10.4. Non-bleeding complications include puncture-related injury, local arterial injury (perforation, dissection, occlusion), embolization requiring intervention, rethrombosis, pericatheter thrombosis requiring unexpected additional intervention, reperfusion injury, compartment syndrome, renal failure, acute myocardial infarction, etc.
10.5. An unexpected amputation (ie, caused by distal emboli) or an increase in the level of amputation as a direct result of the revascularization procedure is regarded as a major complication. Any adverse effect occurring during the time period beginning with the diagnostic arteriogram to 24 hours after revascularization is defined as a procedure-related complication
10.6. Other adverse events that are detected more than 24 hours after revascularization may also be procedure-related (acute renal failure, delayed embolization, or hematoma from the intervention or access site)
Overall trial start date
01/01/2009
Overall trial end date
31/12/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Symptomatic lower limb(s) ischaemia: acute, categories IIA or IIB (the Rutherford classification of acute limb ischaemia), onset of symptoms: 14 days or less
2. Symptomatic subacute lower limb ischemia: categories 3-6 (the Rutherford classification for chronic limb ischaemia), severe claudication, critical limb ischemia, ischemic tissue defect, rest ischemic pain, symptoms duration: from 15 days to 3 months
3. Aged 18 years and over
4. Written informed consent given prior to study entry (or court agreement in unconscious patient)
5. Occluded graft and/or native artery supplying lower limb (supratibial location, lumen diameter 4 mm or more at the site of occlusion, stented or non-stented, with or without calcifications, with or without additional infrapopliteal occlusions/stenoses)
6. Diagnosis of vascular occlusion on digital subtraction angiogram after informed consent is obtained
7. Ability to traverse the occlusion intraluminally with guidewire
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300
Total final enrolment
316
Participant exclusion criteria
1. Serious hemodynamic circulatory incompetence contraindicating application of x-ray contrast material
2. Anatomy excluding endovascular approach and treatment
3. Category III acute lower limb ischemia (irreversible)
4. Occluded vessel diameter less 4 mm, arterial spasm resistant to nitroglycerine
5. Written informed consent or court agreement were not obtained
6. Situation when primary surgical approach is necessary
Recruitment start date
01/04/2009
Recruitment end date
30/04/2015
Locations
Countries of recruitment
Czech Republic
Trial participating centre
University Hospital and 3rd Medical Faculty of Charles University
Cardiovascular Centre
Srobarova 50
Prague
100 34
Czech Republic
Sponsor information
Organisation
Charles University
Sponsor details
Charles University Research Program Q38
Cardiocenter
Third Faculty of Medicine
Ruská 87
Prague
100 00
Czech Republic
Sponsor type
University/education
Website
Funders
Funder type
Other
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a peer reviewed journal.
IPD Sharing plan:
The study protocol, study report and datasets generated during and/or analysed during the current study are available upon request from miroslav.bulvas@fnkv.cz
Intention to publish date
31/03/2019
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/30955402 (added 15/04/2019)
Publication citations
Additional files
- ISRCTN15496770_PIS_08May17.docx Uploaded 11/05/2017