Design of clinical prospective study: application of gene, cell therapy and indirect revascularization for treatment of patients with non-reconstructive chronic lower limb ischemia

Abstract

The aim — to improve the results of surgical treatment of patients with chronic critical lower limb ischemia.Materials and methods. To organize the study, we chose the open controlled method of parallel groups. The study was planned and conducted as an open prospective randomized and controlled trial. The study was conducted in four stages: 1st (screening, up to 2 weeks) — evaluation of the possibility of involvement in the study. At this stage all examinations of patients were carried out; 2nd (2 days) — signing informed consent, distribution of the patients to the treatment groups; 3rd (1.5 months) — treatment; 4th (3 years) — observation. The study involved patients whose vascular bed surgical reconstruction was impossible due to: the presence of prolonged occlusion of the femoral artery with the transition to the distal bed; destruction of vessels of distal segments with unfavorable prognosis; previously performed reconstructive interventions on the arteries of the lower extremities, which did not eliminate chronic ischemia due to the impossibility of repeated surgery; decompensation of somatic pathology that could interfere with surgery.Results and discussion. 110 patients were selected for treatment. The patients were divided into three groups according to the treatment method: 1st — 48 patients who underwent revascularization osteotreopenia as an operation of indirect revascularization, 2nd — 21 patients who were administered endothelial cell growth factor drug for stimulation of their own angiogenesis, 3rd — 41 patients in whom subcutaneous fat sampling, cultivation and transplantation of autologous mesenchymal cells were performed according to proposed by us method. To compare the main endpoints of the study, we created a control group of patients, who had previously undergone the treatment by standard methods in the clinic. The criteria for inclusion in the treatment groups and control group did not differ. All patients in the treatment groups had a high level of pain (on average > 70 mm on a visual analog scale) in the affected limb. The most common associated pathologies were hypertension and coronary heart disease. There was no statistically significant difference in the anamnestic data. Many patients had a history of revascularization attempts (> 50 % had one attempt, 20 % had two or more), 42 % had previous amputations including 26.4 % of small amputations and 10.9 % of above‑knee amputations. The most common reason why patients in the treatment groups were not subject to the revascularization procedure was the technical impossibility of intervention (56.4 %), less common reason — the inappropriateness (33.6 %), which was evaluated on the Finnvasc scale.Conclusions. Critical lower limb ischemia is the most severe form of peripheral artery disease and is associated with a high risk of amputation of the affected limb and death. Three groups of patients, comparable in age, sex ratio, concomitant pathologies and clinical characteristics of the underlying disease, were selected for the prospective study. To compare the effectiveness of our treatment we selected a control group of patients retrospectively, by case histories, according to the inclusion criteria which were the same for all groups. This group was somewhat artificially created, as it consisted only of selected patients comparable to persons in treatment groups by age, comorbidities and underlying disease, as well as those patients whose treatment outcomes could be traced over a 3‑year follow‑up period.