Flow Measurement and Ultrasound for Critical Limb Ischemia

(PATENT Trial)

Overseen By Anne Waaler

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medistim ASA

Disqualifiers: Artificial conduit, Non-atherosclerotic lesions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness and safety of a new method for assessing blood flow and using ultrasound images during vein bypass surgeries in the lower leg. It focuses on individuals with critical limb ischemia, a condition causing severe pain, sores, or tissue damage in the legs due to poor blood flow. The Peripheral Bypass Trial for Completion Control tests the success of these surgeries over a year to evaluate blood flow maintenance. Individuals with persistent leg ulcers or rest pain for over two weeks due to blocked arteries, and who have suitable veins for the procedure, may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage advancements in medical care.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that flow measurement and ultrasound for critical limb ischemia are safe?

Research has shown that lower extremity bypass surgery (LEB) commonly treats symptoms of peripheral artery disease. Understanding the safety of this procedure is crucial. Studies have found that while LEB is effective, it carries some risks.

One study found that another treatment, peripheral vascular interventions (PVI), results in fewer complications within 30 days post-procedure compared to LEB. This suggests LEB might be more challenging for the body shortly after surgery. Another source notes that certain factors can predict poor outcomes, especially in patients with severe artery blockages in the legs and feet.

However, many patients undergo LEB successfully and experience symptom relief. Discussing personal risks and benefits with healthcare providers is important before deciding to join a trial involving this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Peripheral Bypass Trial for Completion Control because it explores the use of flow measurement and ultrasound to improve outcomes for patients with critical limb ischemia. Unlike standard treatments such as angioplasty or stenting, which focus on opening up blocked arteries, this trial investigates the effectiveness of ensuring primary patency of lower extremity vein bypass grafts at one year. By potentially improving the success rate of bypass grafts, this approach could offer better long-term results and reduce the need for repeat interventions.

What evidence suggests that flow measurement and ultrasound are effective for critical limb ischemia?

Research has shown that lower extremity bypass surgery effectively treats severe blood flow problems in the legs, known as chronic limb-threatening ischemia (CLTI). Studies have found that this surgery reduces the risk of needing an amputation within 30 days and increases the chances of living longer over five years. Reviews comparing bypass surgery with other treatments suggest it can be more effective, especially if other procedures have been tried before. Patients who undergo this surgery often experience positive outcomes, such as maintaining open blood vessels over time. This trial will specifically assess the patency of lower extremity vein bypass grafts at one year, indicating that bypass surgery is a strong option for improving blood flow in severe cases of CLTI. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with critical limb ischemia, a severe obstruction of the arteries which drastically reduces blood flow to the extremities, causing pain and skin ulcers or gangrene. Participants must understand the study, be willing to follow its rules and attend follow-ups. They need an adequate target artery below their knee but above their ankle and have a vein available for grafting.

Inclusion Criteria

I understand the study and agree to follow its rules and attend all appointments.

My leg's blood flow area needing treatment has a good target spot for connection below the knee.

I have leg pain at rest, gangrene, or a non-healing leg ulcer due to poor blood flow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Immediate Post-operative

Participants undergo vein bypass surgery and immediate post-operative monitoring with flow measurement and ultrasound imaging

1 week

Follow-up

Participants are monitored for primary graft patency, freedom from repeat graft intervention, graft thrombosis, or clinically significant stenosis

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Peripheral Bypass Trial for Completion Control

Trial Overview The study tests MiraQ with Transit-Time Flow Measurement (TTFM) alongside L15 High Frequency Ultrasound (HFUS) probes in patients undergoing bypass surgery on veins below the knee and above the ankle. It aims to validate these methods for assessing blood flow and imaging during surgery.

How Is the Trial Designed?

Group I: Patency of lower extremity vein bypass grafts Experimental Treatment 1 Intervention

Primary patency of lower extremity vein bypass grafts at one year

Peripheral Bypass Trial for Completion Control is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Peripheral Vascular Bypass for:

• Peripheral Artery Disease (PAD)
• Critical Limb Ischemia (CLI)
• Claudication

Approved in European Union as Lower Extremity Bypass for:

• Peripheral Artery Disease (PAD)
• Critical Limb Ischemia (CLI)
• Claudication

Approved in Canada as Peripheral Vascular Bypass for:

• Peripheral Artery Disease (PAD)
• Critical Limb Ischemia (CLI)
• Claudication

Who Is Running the Clinical Trial?

Medistim ASA

Lead Sponsor

Trials

4

Recruited

1,700+

Published Research Related to This Trial

In a study of 42 patients with stage IIb peripheral occlusive arterial disease (POAD), femoro-popliteal bypass surgery significantly improved blood flow in the operated leg, with measurable increases observed up to one year post-surgery.

Interestingly, the surgery also led to a significant increase in blood flow in the non-operated leg, suggesting a systemic effect of the procedure, while improvements in walking distance and other vascular parameters were also noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Noninvasive studies of macro- and microcirculation in follow-up of femoropopliteal bypass operation in IIb peripheral arterial occlusive disease]. Scheffler, P., Gross, J., Dabringhaus, S., et al.[2016]

In a study of 197 patients undergoing infrainguinal bypass operations for critical ischemia, operative flow measurements were found to be the most powerful predictor of graft patency and limb salvage, outperforming traditional angiography.

The study revealed that PTFE grafts failed to remain patent at flow rates below 50 ml/min, while vein grafts could remain patent at much lower flow rates of 10 ml/min, highlighting the importance of flow measurement in surgical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative flow measurement of distal runoff: a valid predictor of outcome of infrainguinal bypass surgery. Stirnemann, P., Ris, HB., Do, D., et al.[2004]

In a study of 150 patients with peripheral arterial disease (PAD) undergoing coronary artery bypass grafting (CABG), 60.6% experienced symptom progression to ischemic rest pain within the first week after surgery.

Factors such as a low ankle-brachial index (ABI), prolonged cardiopulmonary bypass time, and low hematocrit levels during and after surgery were found to be independently associated with this symptom progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cardiac surgery with cardiopulmonary bypass on symptom progression in the early postoperative period in patients with peripheral arterial disease. Sevuk, U., Istar, H., Bahadir, MV.[2022]

Femorotibial and femoropopliteal bypass surgeries are effective methods for revascularizing severely ischemic lower extremities, with a low incidence of delayed graft occlusion.

Tibial bypasses, in particular, have shown to provide effective and prolonged revascularization, allowing for limb salvage and reducing the need for primary amputation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of long-term results of 364 femoropopliteal or femorotibial bypasses for revascularization of severely ischemic lower extremities. Reichle, FA., Tyson, RR.[2019]

In a study of 155 claudicants undergoing peripheral bypass surgery with an average follow-up of 8.6 years, major vascular events occurred in 59 patients, highlighting a significant annual risk increase of 3.5%.

Key predictors of late vascular morbidity and mortality included hypertension, diabetes, and cardiac disease, with cardiac disease being a particularly strong risk factor for mortality (HR 3.3).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular morbidity and mortality during long-term follow-up in claudicants selected for peripheral bypass surgery. Dawson, I., Sie, RB., van der Wall, EE., et al.[2019]

Duplex ultrasound surveillance significantly improves the patency of femorofemoral bypass grafts by accurately identifying stenosis and potential failures, with a primary graft patency of 62% at 5 years after surgery.

Repairing duplex-detected stenosis led to an impressive assisted-primary patency rate of 88% at 5 years, highlighting the importance of regular monitoring and timely intervention in maintaining graft function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duplex ultrasound criteria for femorofemoral bypass revision. Stone, PA., Armstrong, PA., Bandyk, DF., et al.[2016]

Intraoperative blood flow measurements using papaverine flow can predict the long-term success of above-knee prosthetic femoropopliteal bypass, with a flow of 500 mL/min or less linked to significantly lower patency rates at 2 and 5 years.

Smoking and poor preoperative run-off scores are independent risk factors that further decrease patency rates, suggesting that patients in these categories may have less favorable outcomes with prosthetic bypass procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flow measurement before and after papaverine injection in above-knee prosthetic femoropopliteal bypass. Pedersen, G., Laxdal, E., Amundsen, SR., et al.[2016]

The Doppler ultrasound velocity meter effectively assesses blood flow in patients with chronic obliterative arterial disease, showing a strong correlation between ankle pressure and muscle blood flow during isotope clearance studies.

In a study of 17 patients, the Doppler indices measured at rest and after exercise provided consistent patterns that reflected the severity of vascular occlusion and correlated well with patients' exercise tolerance, making it a valuable tool for monitoring peripheral vascular disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The assessment of peripheral vascular insufficiency with the doppler flowmeter. Abramowitz, I.[2014]

Echocardiographic evaluation, including resting left ventricular ejection fraction and dipyridamole stress test results, is a strong predictor of both early and late cardiac complications in patients undergoing limb revascularization, outperforming standard clinical evaluations.

In this study of 110 patients, those with negative dipyridamole stress tests and good left ventricular function did not experience any cardiac complications, highlighting the potential for echocardiography to identify low-risk patients for safer surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk stratification of patients undergoing peripheral vascular revascularization by combined resting and dipyridamole echocardiography. Rossi, E., Citterio, F., Vescio, MF., et al.[2019]

In a study of 118 above-knee prosthetic femoropopliteal bypass procedures, a surveillance program using color duplex ultrasound identified significant graft-related stenotic lesions in 9.7% of scans, allowing for timely treatment and improving outcomes.

The study found that treated grafts had a lower occlusion rate of 21% compared to 41% for all grafts, suggesting that monitoring and addressing stenoses can enhance the longevity of these bypasses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surveillance of above-knee prosthetic femoropopliteal bypass. Aune, S., Pedersen, OM., Trippestad, A.[2019]

In a study of 49 patients with chronic limb-threatening ischemia, combining superficial femoral artery endovascular therapy with popliteal-to-distal bypass showed high limb salvage rates of 97% at 1 year and 92% at 3 years, indicating its effectiveness in preventing limb loss.

The procedure demonstrated durable graft patency, with primary patency rates of 44% at 1 year and 39% at 3 years, alongside good wound healing outcomes of 67% at 6 months and 83% at 12 months, suggesting it is a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of combined superficial femoral artery endovascular therapy with popliteal-to-distal bypass: A paradigm shift in surgical open bypass for chronic limb-threatening ischemia. Kobayashi, T., Hamamoto, M., Okazaki, T., et al.[2021]

In a study of 217 patients undergoing popliteal or distal revascularization, early and late blood flow measurements were found to be crucial for assessing hemodynamic control and predicting post-operative outcomes.

The study highlights the importance of evaluating peripheral arterial resistance and recommends using a vasodilative test to better understand blood flow dynamics, which correlates with clinical results and can help identify potential post-operative failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Per-operative blood flow measurement, complement to arteriography. Control and prognostic appreciation method (author's transl)]. Nicaise, H., Marçon, JM., Clément, C., et al.[2007]

In a study of 60 patients with severe atherosclerotic lesions and critical lower limb ischemia, using a free autovenous graft with destructed valves during femoropopliteal bypass surgery reduced early postoperative complications and remote graft thrombosis by 13.3%.

This innovative technique also led to improvements in patients' physical and mental health components by 7.9% and 3.1%, respectively, indicating its efficacy in enhancing overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Free autovenous graft with destructed valves in treatment of severe ischemia of lower extremities]. Sukhovatykh, BS., Belikov, LN., Sukhovatykh, MB., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10964324/

Comparison of lower extremity bypass and peripheral ... There is a relative lack of comparative effectiveness research on revascularization for patients with chronic limb-threatening ischemia (CLTI).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37207790/

Comparison of lower extremity bypass and ... - PubMed In the Vascular Quality Initiative-linked Medicare registry, LEB vs PVI for CLTI was associated with a lower risk of 30-day amputation and 5-year all-cause ...

3. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.114.013440

The Contemporary Safety and Effectiveness of Lower ... Impact of Rural Status on Lower Extremity Bypass Outcomes for Patients With Chronic Limb Threatening Ischemia, Annals of Vascular Surgery, 117, (44-55), (2025).

4. jvascsurg.org jvascsurg.org/article/S0741-5214(23)01591-4/fulltext

A systematic review and meta-analysis of primary bypass ... A systematic review was conducted to compare the outcomes of primary bypass and bypass surgery after endovascular treatment.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0741521423021729

Outcomes of lower extremity arterial bypass using the ... Two HAVs were sewn together to attain the needed bypass length in 24 patients (83%). Bypasses were to tibial arteries in 23 patients (79%) and to the popliteal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4652630/

The Contemporary Safety and Effectiveness of Lower ... Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) or peripheral vascular interventions (PVI).

7. jvascsurg.org jvascsurg.org/article/S0741-5214(16)30159-8/fulltext

The Contemporary Safety and Effectiveness of Lower ... Conclusions. Peripheral endovascular intervention (PVI) in comparison with lower extremity bypass (LEB) is associated with fewer 30-day procedural complications ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4075947/

Defining risks and predicting adverse events after lower ... Here we review the risks of surgical bypass in patients with CLI, with particular emphasis on the identification of preoperative variables that predict poor ...

9. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000001251

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/ ... ... critical limb ischemia predicts poor outcome after lower extremity bypass. J Vasc Surg. 2011;54:730–735; discussion 735-736. Go to Citation.