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

Trial Summary

What is the purpose of this trial?

The goal of the study is to identify and validate flow measurement and ultrasound images in patients undergoing vein bypass surgery below-knee and above ankle

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 data supports the effectiveness of this treatment for critical limb ischemia?

Research shows that combining endovascular therapy (a minimally invasive procedure to open blocked blood vessels) with bypass surgery can improve blood flow in patients with severe limb-threatening conditions. Additionally, using ultrasound to monitor blood flow during and after surgery helps predict the success of the procedure and guide necessary adjustments. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The studies suggest that bypass surgeries, like femoropopliteal and femorotibial bypasses, are generally safe for revascularizing severely ischemic limbs, with a low incidence of complications. However, patients with advanced peripheral vascular disease may have an increased risk of heart-related issues during and after surgery. ^{2 6 7 8 9}

How is the Peripheral Bypass Trial for Completion Control treatment different from other treatments for critical limb ischemia?

This treatment is unique because it uses noninvasive ultrasound techniques to measure blood flow during and after bypass surgery, which helps predict the success of the procedure and monitor recovery. This approach allows for real-time assessment and adjustment, potentially improving outcomes compared to traditional methods that do not use such detailed flow measurements. ^{4 10 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

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 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]

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]

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]

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]

References

1. England 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Duplex ultrasound criteria for femorofemoral bypass revision. [2016]

3. France pubmed.ncbi.nlm.nih.gov

[Per-operative blood flow measurement, complement to arteriography. Control and prognostic appreciation method (author's transl)]. [2007]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[Noninvasive studies of macro- and microcirculation in follow-up of femoropopliteal bypass operation in IIb peripheral arterial occlusive disease]. [2016]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Free autovenous graft with destructed valves in treatment of severe ischemia of lower extremities]. [2018]

6. Italy 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Risk stratification of patients undergoing peripheral vascular revascularization by combined resting and dipyridamole echocardiography. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Vascular morbidity and mortality during long-term follow-up in claudicants selected for peripheral bypass surgery. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Intraoperative flow measurement of distal runoff: a valid predictor of outcome of infrainguinal bypass surgery. [2004]

11. United States pubmed.ncbi.nlm.nih.gov

Flow measurement before and after papaverine injection in above-knee prosthetic femoropopliteal bypass. [2016]

12. South Africa pubmed.ncbi.nlm.nih.gov

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

13. England pubmed.ncbi.nlm.nih.gov

Surveillance of above-knee prosthetic femoropopliteal bypass. [2019]