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Edits based on 6/17/09 meeting.
Clinical protocol
ASPECT-I is a prospective single-center pilot clinical trial conducted at the Cleveland Clinic Foundation(CCF, Cleveland, Ohio). The primary aim of the study is to understand and quantify the dynamically changing arterial environment in patients suffering from peripheral artery disease in lower extremities before and after endovascular stenting. CCF will designate the clinical principal investigator (PI) who shall perform and/or oversee the screening, selection, consent, enrollment, and treatment of subjects with endovascular stents and follow them for two years.
Patient enrollment:
Study subjects will be recruited from the Departments of Vascular Surgery and Cardiology and the Section of Vascular Medicine. The study population will include patients with Rutherford Class
All subjects will provide written informed consent for the study, including performance of IVUS concurrent with angiography. Enrolled subjects will receive the quality of life (QoL) assessment short form-36 (SF-36) and
Inclusion and exclusion criteria:
The inclusion criteria will be as follows:
1. Signed written informed consent.
2. Men or women aged 18 years or older with non-invasive laboratory evidence of PAD who may benefit from an intervention (Rutherford scale
3. Clinically indicated for treatment of symptomatic PAD resulting from significant vascular stenosis with the use of an endovascular stent . PTA may be used in conjunction with stenting[s1] . Significant stenosis will be defined as angiographic stenosis > 50% or Doppler velocity > 2.4 m/s.
4. Native lower extremity artery with previously untreated target lesion.
5. Target lesion located at least three centimeters proximal to the superior edge of the patella.
6. Patent infrapopliteal and popliteal artery, i.e., single vessel runoff or better with at least one of three vessels patient (<50% stenosis) to the ankle or foot
The exclusion criteria will include:
1. Life expectancy less than 2 years.
2. Contraindication to angiography (creatinine >2.5[MJ5] , or eGFR<60).
3. Acute limb ischemia, defined by a significant change in symptoms (one category on the Rutherford scale within the previous 14 days.
4. Angiographic criteria for acute limb ischemia[MJ6], including thrombus or meniscus sign.
5. Concurrent oral anticoagulant therapy that cannot be safely withheld.
6. Extensive tissue loss (Rutherford 5 or 6) or gangrene[MJ7] .
7. Participation in any investigational drug or device study
8. Bleeding diathesis.
9. Inability to administer contrast dye that encompasses dye allergy.
10. Pregnancy.
11. Unwilling to comply with study protocol required follow up.
12. Illness which, in the opinion of the PI, limits life expectancy to 1 year or less.
13. Subjects who have undergone prior PTA of a non-target lesion in the past 6 months or of a target lesion in the past 3 months
14. Presence of inflow restrictions that cannot be treated
15. Has significant stenosis or occlusion of inflow tract not successfully treated before the treatment of the target lesion. Treatment of lesions in the iliac and/or common femoral arteries that require treatment may be treated during the index procedure, but must be successfully treated prior to the point of enrollment.
16. Treatment of culprit lesion may not include adjunctive therapies including atherectomy or PolarCath.
Clinical data [PDB2] will be entered in a web-based (intranet) case report form, abstracted electronically into a complaint[MJ8] database during a single office visit. Demographic variables will include age, gender, and race. Baseline medical co-morbidities will be recorded and entered into the database, including hypertension, diabetes (Type I or II), coronary artery disease, chronic renal insufficiency, chronic obstructive lung disease, and obesity. A history of smoking, ethanol and family history of coronary or peripheral vascular disease will be elicited. The severity of the clinical presentation will be graded using the Rutherford criteria. Previously drawn laboratory studies will be abstracted from the CCF electronic database. Pre-procedural laboratory studies performed for this study (if not recently done, < 2months) will include: fasting blood glucose, HbA1c (in diabetics), and cholesterol profile. Additionally, these assays will be performed by clinical chemistry using standard assays as well.
Subjects will undergo a series of diagnostic procedures to determine the vessel patency and quantify the mechanical environment under several loading conditions during pre-procedural, post-procedural and follow-up visits (see Appendix A). We will use Computer Tomography – Angiography (CTA) for obtaining detailed arterial geometry info, Digital X-Ray for stent fracture identification and 2D arterial geometry info, Duplex Ultrasound (DUS) for estimating vessel patency and Intravascular Ultrasound (IVUS) to obtain detailed plaque and vessel information. Clinically, imaging different leg positions would enhance the understanding of how extreme leg movements would induce trauma or injury over time[MJ9]
[Insert time study interval table here]
Human subjects:
1. Study population: The study will comprise subjects aged 18 and above, with a gender and racial mix characteristic of the population with PAD, included in the CCF, Vascular Surgical (IRB-approved) Registry. 2. Informed consent: An Institutional Review Board (IRB) approval will be obtained prior to commencement of any research activity. Because all devices used in this study are FDA approved or cleared, informed consent need only address the risk associated with being a research subject. Informed[MJ10] consent for this study excludes consent for the surgical procedure. Consent for the surgical procedure is the responsibility of the PI at CCF in accordance with his standard of practice and individual institutional requirements (as applicable). The IRB-approved informed consent form will be signed by the subject, or his/her legal representative, as well as by the person who conducted the informed consent process, before care is altered for the purpose of participating in this trial (this includes administration of study-required questionnaires). Standard clinical procedures performed to evaluate a patient for an endovascular intervention may precede the documentation of informed consent. All subjects will provide written informed consent prior to consideration for enrollment. Consent will be obtained at least 24 hours prior to the scheduled intervention.
3. Risks to subjects
Angiography/IVUS: All subjects will be patients for whom lower extremity stenting is planned. The addition of IVUS to the diagnostic regimen is considered to be of little additional risk with some patients receiving IVUS imaging as part of their standard of care. No additional arterial access cannulations will be performed. Given the small caliber of the IVUS probes used for the study of peripheral arteries, the sheath sizes will not be larger than would have been utilized if IVUS were not performed. There will be some additional time required for IVUS interrogation (usually about 20 minutes), but the procedures are performed with local anesthetic only. Further, the patients might be briefly exposed to radiation during the imaging procedure. In addition, CTA will expose the patients to contrast agents thereby increasing the risk of allergic reaction or contrast nephropathy. Thus, the additional risk to the patient is thought to be only at a relatively small amount.
4. Potential benefits of the proposed research to the subjects and others: The volunteers in this clinical are not expected to have any direct benefit from their participation. Data generated by this study will hopefully provide a wealth of data for clinicians and researchers for refining endovascular stenting within the lower extremity arterial beds.
5. Importance of the knowledge to be gained: Presently, lower extremity stent conditions are not fully understood. This study will better define stent boundary conditions and hopefully allow predictors of stent success to be discovered.
6. Inclusion of women: Women will be included in each of the studies proposed within this application. They will be included at the ratio observed in the referral base for the Department of Vascular Surgery at the CC (approximately 3:7 to 2:8, F:M, depending on the number of subjects with severe PAD, a symptom subset over-represented by males).
7. Inclusion of minorities: Minorities will be included in each of the studies proposed. For the pilot study, the minority representation will mirror the referral base for those departments at the CC involved in the care of patients with PAD.
Data and safety monitoring plan:
The studies will be performed in accordance with the Institutional Review Board (IRB) of CCF and the Code of Federal Regulations (CFR) Title 21, Part 50. The VSACC at CCF will be also managing and monitoring the study conduct. HIPAA guidelines (21 CFR Title 11) will be adhered to. Furthermore, all adverse or unexpected events will be carefully reviewed to discern the cause of the events. However, any adverse event during the conduct of study will result in careful review and notification to the IRB. Serious adverse events (see Appendix B) due to the study protocol and not attributable to other patient factors will lead to halting of the study and reappraisal.
Appendix A: Diagnostic procedures
Pre-Operative/Screening
Procedural
Discharge
1-Month
6-Month
12-Month
24-Month
Other follow-up time points
Imaging orientations
Appendix B: Adverse Events
Cardiovascular
Pulmonary
Renal
GI
Neuro
Wound
Other
[s1]Consider defining this more stringently such as by adding angiographic criteria for appropriate intervention such as ≥70 stenosis.
[PDB2]I think we’ll want some follow-up clinical information.
[PDB3]Possibly obtain this if available?
[PDB4]Likely do not need contrast
[PDB5]I don’t believe Discharge duplex is covered by patient insurance...
[PDB6]This will open the possibility to re-IVUS patients undergoing angiography within 24M time span.
[s1]At the teleconference Wednesday we talked about Rutherford 2-4. The concern with class 1 was that often they are treated conservatively, without stenting. [MJ2]These are NOT synonymous QOL tools....and are usually used together. [MJ3]Not sure I understand this. [MJ4]I don't understand what this means. [MJ5]Better to use eGRFR <60, for example. [MJ6]Delete this...ALI is a CLINICAL diagnosis, not an arteriographic one. If you mean that a meniscus sign is noted, suggesting acute embolic occlusion, that is a different story. [MJ7]What about Rutherford 4? [MJ8]??? [MJ9]You should reference the study time interval table here. [MJ10]FDA approved.....but not necessarily ON LABEL? Can a 510(k) approved device be used in this study? [MJ11]ABI must be performed at baseline and at follow up. [MJ12]This does not need to be performed at discharge, but rather within 30 days of the procedure. [MJ13]Why are you doing this???If you want to show improved walking distance, get a pre-procedure graded treadmill test, and then another at 6 and 12 momths---or, do a 6 min walk test. Both have been far better validated than 48 pedometer use, particularly since you did not include this pre-intervention. [MJ14]These need to be reorganized [MJ15]Related to the index procedure [MJ16]What incision????
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ASPECT Study >
Global Clinical Protocol v.1 |
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Edited to include comments from M. Jaff and S. Brooks.