Comparison of the impact of autologous cell therapy and conservative standard treatment on tissue oxygen supply and course of the diabetic foot in patients with chronic limbthreatening ischemia: A randomized controlled trial

Chronic limb-threatening ischemia (CLTI) is a new term
used for the end stage of peripheral arterial disease instead of the
older term “critical limb ischemia”. Management of CLTI has
been recently summarized in a guideline document, ‘Global
Vascular Guidelines’ (1). This paper concludes that there is
strong evidence to support that all patients with CLTI should use
antiplatelet agents, statins, especially after any revascularization;
and moderate evidence has been reported for the use of
clopidogrel, rivaroxaban or vitamin K antagonists´. These
guidelines also suggest that the choice of the optimal
revascularization technique of CLTI should be decided based
on PLAN concept (Patient risk estimation, Limb staging,
ANatomic pattern of the disease) (1) and by local expertise
(2). Obstruction of the common femoral artery or long
occlusions above the knee are usually suitable for surgical
approach (3). There are still many patients with the most
severe stages of CLTI who are not suitable for any kind of
standard revascularization, and suffer from high rates of major
amputation and mortality. These patients are usually classed as
“no-option CLTI” (4).
Common revascularization technique of CLTI includes
percutaneous transluminal angiography (PTA) or bypass with
increasing preference for endovascular treatment, whereas these
methods are not sufficient in all patients and some patients can
develop stenosis or occlusion after these procedures (1, 5).
Autologous cell therapy (ACT) is a new experimental
treatment and is being increasingly researched as an option in
those with CLTI (6). It has been suggested that if it is applied
appropriately and followed by other comprehensive therapy
(7–9) these “no-option” patients could have a therapeutic
benefit from ACT despite the fact that the level of evidence for
the effect of this treatment in vascular guidelines is described as
low to moderate (1, 10).
Recently published meta-analyses and reviews concluded
that ACT is a safe method for the treatment of CLTI in
patients with diabetic foot disease and significantly increases
main ischemia parameters including ankle-brachial index (ABI),
toe-brachial index (TBI), transcutaneous oxygen pressure
(TcPO2) and laser doppler flowmetry (7, 9, 11, 12). The results
from randomized controlled trials on limb salvage and the effect
of ACT on amputation-free survival (AFS) are variable. Some of
the studies reported a decrease in amputation rates after cell
therapy (13–15), whereas others reported no significant impact
of ACT on major amputation or AFS (16, 17).
The aim of our study was to compare the effect on tissue
oxygenation and clinical outcome of ACT versus conservative
standard treatment (ST) in patients with diabetic foot not
eligible for standard revascularization (NO-CLTI). Other
objectives of the study were quality of life assessment and side
effects of ACT.