Peripheral Microvascular Resistance as a Predictor for Limb Salvage

Peripheral Arterial Disease Clinical Trial

Official title:

Peripheral Microvascular Resistance as a Predictor for Limb Salvage in Post-Intervention Critical Limb Ischemia Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06014242
• Other study ID #: Pro2021-0681
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 25, 2024
• Est. completion date: July 15, 2025

Study information

• Verified date: June 2024
• Source: Hackensack Meridian Health
• Contact: Patricia Arakelian, RN
• Phone: 5519962000
• Email: patricia.arakelian[@]hmhn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Salvaging a threatened limb is the key therapeutic objective for patients with critical limb ischemia, and the achievement of limb salvage is an independent predictor of patient morbidity and mortality. Despite successful primary endovascular or surgical intervention, the corresponding symptoms of rest pain and/or non-healing ulceration in some patients may continue, and amputation in these patients is unavoidable. It is hypothesized that the functional integrity of the peripheral vascular microcirculation may be impaired in these patients. However, there are currently no techniques that allow direct quantification and visualization of the microcirculation due to the micro-vessel invisibility under angiography.

In the coronary circulation, coronary flow reserve (CFR) indicates the capacity for maximal hyperemic blood flow and reveals impaired coronary microvascular function. Studies have shown the clinical significance of measuring microvascular resistance to predict myocardial salvage after myocardial infarction. The study will explore whether this concept of coronary flow reserve can be applied peripherally to patients with critical limb ischemia in order to determine whether measuring peripheral vascular flow reserve can determine the integrity of the microcirculation to predict limb salvage after endovascular intervention.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: July 15, 2025
• Est. primary completion date: July 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic critical limb ischemia (Rutherford 4-6).

• Age =18 years

• Ability and willingness to sign the IRB approved Informed Consent form

Exclusion Criteria:

• Non-reconstructable chronic total occlusive disease of the proximal inflow vessels that would make flow reserve measurements impossible.

• Non-salvageable lower extremity due to infection or overwhelming per-existing tissue loss (most critical Rutherford 6 patients).

• Inability to understand the study or a history of non-compliance with medical advice;

• History of any cognitive or mental health status that would interfere with study participation;

• Currently enrolled in any pre-approval investigational study.

• Female subjects who are pregnant or nursing or planning to become pregnant within the study period;

• Known sensitivity to contrast media, which can't be adequately pre-medicated;

• Expected life span less than 6 months.

• Unable to read/understand/sign the English Language consent form

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Diagnostic Test:
• Peripheral vascular flow reserve measurement
Peripheral arterial (below knee popliteal and above the level of ankle distal tibial) thermodilution curves will be obtained. One of the distal tibial arteries (anterior tibial, posterior tibial or peroneal artery, whichever reaches the most distal part of the foot in the run off) will be picked for measurements. At room temperature, 3 ml of saline will be injected brisk manually to determine the peak arterial flow, presented as mean transit time (Tmn). Resting Tmn will be performed and averaged by triplicate measurements at baseline. Then maximal hyperemia will be induced by intra-arterial injection of 30 mg papaverine through the guiding catheter, then 3 ml of saline will be injected to get hyperemic Tmn averaged by triplicate measurements. The guidewire will be kept in a fixed position during the series of measurements. Peripheral vascular flow reserve was calculated as resting Tmn divided by hyperemic Tmn (Fukunaga 2015).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hackensack Meridian Health	Abbott Medical Devices

References & Publications (5)

Crea, F., Lanza, G.A. and Camici, P.G., 2014. Mechanisms of coronary microvascular dysfunction. In Coronary Microvascular Dysfunction (pp. 31-47). Springer, Milano.

Fukunaga M, Fujii K, Kawasaki D, Nishimura M, Horimatsu T, Saita T, Miki K, Tamaru H, Imanaka T, Naito Y, Masuyama T. Vascular flow reserve immediately after infrapopliteal intervention as a predictor of wound healing in patients with foot tissue loss. Circ Cardiovasc Interv. 2015 Jun;8(6):e002412. doi: 10.1161/CIRCINTERVENTIONS.115.002412. — View Citation

Kern MJ. Coronary physiology revisited : practical insights from the cardiac catheterization laboratory. Circulation. 2000 Mar 21;101(11):1344-51. doi: 10.1161/01.cir.101.11.1344. — View Citation

McGinn, A.L., White, C.W. and Wilson, R.F., 1990. Interstudy variability of coronary flow reserve. Influence of heart rate, arterial pressure, and ventricular preload. Circulation, 81(4), pp.1319-1330. Nahser Jr, P.J., Brown, R.E., Oskarsson, H., Winniford, M.D. and Rossen, J.D., 1995. Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation, 91(3), pp.635-640. Payne, A.R., Berry, C., Doolin, O., McEntegart, M., Petrie, M.C., Lindsay, M.M., Hood, S., Carrick, D., Tzemos, N., Weale, P. and McComb, C., 2012. Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction. Journal of the American Heart Association, 1(4), p.e002246. Camici, P.G., d'Amati, G. and Rimoldi, O., 2015. Coronary microvascular dysfunction: mechanisms and functional assessment. Nature Reviews Cardiology, 12(1), p.48.

Pijls NH, De Bruyne B, Smith L, Aarnoudse W, Barbato E, Bartunek J, Bech GJ, Van De Vosse F. Coronary thermodilution to assess flow reserve: validation in humans. Circulation. 2002 May 28;105(21):2482-6. doi: 10.1161/01.cir.0000017199.09457.3d. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of the peripheral flow reserve	To assess whether peripheral flow reserve can predict the success rate of limb salvage in critical limb ischemia patients after endovascular intervention. Assessed by any amputation (major or minor) at 6 months post-endovascular intervention.	6 months post-endovascular intervention
Secondary	Symptom resolution - Ulcer healing (1m)	Ulcer healing: changes in the number and extent of leg ulcers compared to baseline.	1 month post-endovascular intervention
Secondary	Symptom resolution - Ulcer healing (6m)	Ulcer healing: changes in the number and extent of leg ulcers compared to baseline.	6 months post-endovascular intervention
Secondary	Number of patients with Symptom resolution - Pain (1m)	Resolution of rest pain and alteration in visual analogue pain compared to baseline.	1 month post-endovascular intervention
Secondary	Number of patients with Symptom resolution - Pain (6m)	Resolution of rest pain and alteration in visual analogue pain compared to baseline.	6 months post-endovascular intervention
Secondary	Ankle-brachial index (ABI) (1m)	Improvement in Ankle-brachial index (ABI) compared to baseline. The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. Normal ABI ranges from 1.0 - 1.4, with <0.9 suggesting arterial disease.	1 month post-endovascular intervention
Secondary	Ankle-brachial index (ABI) (6m)	Improvement in Ankle-brachial index (ABI) compared to baseline. The Ankle Brachial Index (ABI) is the systolic pressure at the ankle, divided by the systolic pressure at the arm. Normal ABI ranges from 1.0 - 1.4, with <0.9 suggesting arterial disease.	6 months post-endovascular intervention
Secondary	Toe-brachial index (TBI) (1m)	Improvement in Toe-brachial index (TBI) compared to baseline. The Toe Brachial Index (TBI) is defined as the ratio between the systolic blood pressure in the right or left toe and the higher of the systolic pressure in the right or left arms. TBI = 0.7 is considered normal while TBI < 0.7 is considered abnormal.	1 month post-endovascular intervention
Secondary	Toe-brachial index (TBI) (6m)	Improvement in Toe-brachial index (TBI) compared to baseline. The Toe Brachial Index (TBI) is defined as the ratio between the systolic blood pressure in the right or left toe and the higher of the systolic pressure in the right or left arms. TBI = 0.7 is considered normal while TBI < 0.7 is considered abnormal.	6 months post-endovascular intervention
Secondary	Rutherford classification (1m)	Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene.	1 month post-endovascular intervention
Secondary	Rutherford classification (6m)	Use of The Rutherford classification to assess peripheral artery disease compared to baseline. A 7 category scale is being used with 0 being Asymptomatic and 6 being Ulceration or gangrene.	6 months post-endovascular intervention
Secondary	Transcutaneous oxygen partial pressure (TcPO2) (1m)	Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion).	1 month post-endovascular intervention
Secondary	Transcutaneous oxygen partial pressure (TcPO2) (6m)	Transcutaneous partial pressure of oxygen (TcPO2) will be measured representing the amount of oxygen diffusing outward across the skin (used as a surrogate for arterial perfusion).	6 months post-endovascular intervention
Secondary	Target lesion revascularization (1m)	Need for revascularization (yes/no)	At 1 month post-endovascular intervention
Secondary	Target lesion revascularization (6m)	Need for revascularization (yes/no)	At 6 month post-endovascular intervention