Peripheral Microvascular Resistance as a Predictor for Limb Salvage

NCT06014242 | Withdrawn DMC FDA Device

• 1 other identifier: Pro2021-0681
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Peripheral Arterial Disease

Keywords

Microvascular disease; Microvascular Resistance; Limb Salvage; Peripheral Arterial Disease; critical limb ischemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Symptom resolution - Ulcer healing (1m)

  1 month post-endovascular intervention

• Symptom resolution - Ulcer healing (6m)

  6 months post-endovascular intervention

• Number of patients with Symptom resolution - Pain (1m)

  1 month post-endovascular intervention

• Number of patients with Symptom resolution - Pain (6m)

  6 months post-endovascular intervention

• Ankle-brachial index (ABI) (1m)

  1 month post-endovascular intervention

Study Arms (1)

Peripheral vascular flow reserve measurement

EXPERIMENTAL

Post-procedure peripheral vascular flow reserve by thermodilution will be measured by the pressure wire.

Diagnostic Test: Peripheral vascular flow reserve measurement

Interventions

Peripheral vascular flow reserve measurement DIAGNOSTIC_TEST

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).

Peripheral vascular flow reserve measurement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic critical limb ischemia (Rutherford 4-6).
• Age ≥18 years
• Ability and willingness to sign the IRB approved Informed Consent form

You may not qualify if:

• 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

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Abbott Medical Devices: collaborator

Related Publications (5)

• 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.

  BACKGROUND

• 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.

  PMID: 26019143 BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 12034653 BACKGROUND

• 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.

  PMID: 10725297 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease; Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Officials

• David O'Connor, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: August 28, 2023
• Study Start: September 15, 2025
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share