Clinical study of Unifuzol® in patients with intermittent claudication

• Savina L.V.
• Kovalenko A.L.
• Petrov A.Yu.
• Lukyanchikov V.V.

Abstract

Presented herein are the results of a multicenter double-blind placebo-controlled randomized clinical trial of the safety and efficacy of “Unifuzol^®” (arginine sodium succinate, 1.4% solution for infusion) in 40-to-65-year-old patients with obliterating atherosclerosis of lower limb arteries stage II A according to the classification of A.V. Pokrovsky.

Objective. This study was undertaken to investigate the efficacy and safety of Unifuzol® at a daily dose of 500 ml during 1 course of 10 days and during 2 courses of 10 days each with an interval of 14 days between them.

Patients and methods. The study included a total of 460 patients randomized in a 1:1:1:1 ratio into each treatment group. The primary efficacy parameters were as follows: absolute (in meters) and relative (in %) gain in the pain-free walking distance and maximal walking distance in the treadmill test compared with the baseline measures (the mean value of 2 treadmill tests performed at the screening visit).

Results and discussion. After the 10-day course of therapy, the comparative between-group analysis demonstrated the most pronounced difference for the maximal walking distance measure, which averaged 25 meters (95% CI, p=0.036) 30 days after completion of therapy.

The 20-day therapy cohort showed a difference in the pain-free walking distance, amounting to 23 meters immediately after completion of the 2nd course of therapy and 29 meters 30 days after completion of therapy (p=0.039 and p=0.01, respectively).

Analyzing the significance of intergroup differences for each efficacy variable, the change in the pain-free walking distance was 10 (4%) meters immediately upon completion of the course and 17.8 (8.3%) meters 30 days after completion of therapy, and the change in the maximum walking distance was 13 meters and 22 meters in absolute terms and 4% and 7.6% in relative terms, respectively.

Conclusion. The obtained findings confirmed efficacy of infusion therapy with Unifuzol® in patients with stage II A obliterating atherosclerosis of lower limb arteries in course administration during both 10 and 20 days (10 and 20 infusions, respectively).

Funding. The study was sponsored by the LLC “NTFF POLISAN”, Russia.

Conflict of interest. The authors declare no conflicts of interest.

Authors’ contribution. Study conception and design – Kovalenko A.L.; data collection and handling – Lukyanchikov V.V.; statistical processing – Savina L.V.; draft manuscript preparation – Savina L.V.; manuscript revision – Petrov A.Yu.

For citation: Savina L.V., Kovalenko A.L., Petrov A.Yu., Lukyanchikov V.V. Clinical study of Unifuzol^® in patients with intermittent claudication. Angiology and Vascular Surgery. Journal named after Academician A.V. Pokrovsky. 2024; 30 (2): 22–32. DOI: https://doi.org/10.33029/1027-6661-2024-30-2-22-32

Keywords: obliterating atherosclerosis of lower limb arteries; Unifuzol; intermittent claudication; arginine sodium succinate; infusion therapy; pain-free walking distance; maximum walking distance

References

1. Stepanov Y.M., Kononov I.N., Zhurbina A.I., Filippova A.Y. Arginine in medical practice. Journal of the Ukrainian Academy of Medical Sciences. 2004; 10 (1): 340–352. (in Russian)

2. Böger R.H. The pharmacodynamics of L-arginine. Journal of Nutrition. 2007; 137 (6 Suppl 2): 1650S–1655S. DOI: https://doi.org/10.1093/jn/137.6.1650S

3. Kotelnikov G. P., Shpigel A.S. Evidence-based medicine. Scientifically based medical practice. Samara: SamSMU. 2000; 116. (in Russian)

4. Kalinin R.E., Suchkov I.A., Chobanyan A.A., Nikiforova L.V. Endothelial function in benign and progressive course of periferal arterial disease. Russian Journal of Cardiology and Cardiovascular Surgery. 2021; 14 (2): 189–194. https://doi.org/10.17116/kardio202114021189 (in Russian)

5. Vasiliev A.G., Trashkov A.P., Kovalenko A.L., et al. Evaluation of the specific pharmacological activity of the drug Unifuzol on a model of endothelial dysfunction induced by the administration of N-nitro-L-arginine methyl ester. Experimental and clinical pharmacology. 2016; 79 (11): 11–14. (in Russian)

6. Khotin M.G., Alexandrova O.I., Khorolskaya Yu.I., et al. The effect of the drug “Unifuzol” on the main functional properties of endotheliocytes. Topical issues of fundamental, experimental and clinical morphology: proceedings of the All-Russian Conference of Young Specialists, edited by R.V. Deev. Ryazan: OOP UIT-Top. 2017; 96–98. (in Russian)

7. Toropova Ya.G., Zelenskaya I.A., Pechnikova N.A., et al. The effect of unifuzol on the functional state of the endothelium and microcirculation in the experiment. Experimental and clinical pharmacology. 2018; 81 (5): 7–11. DOI: https://doi.org/10.30906/0869-2092-2018-81-5-7-11 (in Russian)

8. Kurkin D.V., Bakulin D.A., Morkovin E.I., et al. Study of the effect of Unifuzol on cognitive impairment and damage to the hippocampus and cerebral cortex during course administration to rats with bilateral stenosis of the common carotid arteries, causing chronic circulatory failure. S.S. Korsakov Journal of Neurology and Psychiatry. 2023; 123 (3): 1–10. DOI: https://doi.org/10.17116/jnevro20231230311 (in Russian)

9. Valeev V.V., Trashkov A.P., Kovalenko A.L., et al. Prevention and correction of anthracycline-induced angiopathy: an experimental study. P.A. Herzen Journal of Oncology. 2016; 5 (6): 31–34. DOI: https://doi.org/10.17116/onkolog20165631-34 (in Russian)

10. Valeev V.V., Trashkov A.P., Kovalenko A.L., et al. New Sodium L-Arginine Succinate vasodilators in the prevention and treatment of doxyrubicin-induced cardiotoxicity. Pathological physiology and experimental therapy. 2016; 60 (4): 52–57. (in Russian)

11. Stelmakh V.V., Kovalenko A.L., Ketlinskaya O.S., etc. New Sodium L-Arginine Vasodilator Succinate: results on functional Phase I studies. Eksperimentalnaya i Klinicheskaya Farmakologiya. 2018; 81 (10): 8–14. DOI: https://doi.org/10.30906/0869-2092-2018-81-10-8-14 (in Russian)

12. Kalinin R.E., Suchkov I.A., Mzhavanadze N.D., et al. Current aspects of performing treadmill test in patients with peripheral artery disease. Angiology and Vascular Surgery. 2019; 25 (2): 25–33. (in Russian)

13. Momsen A.H., Jensen M.B., Norager C.B., et al. Drug Therapy for Improving Walking Distance in Intermittent Claudication: A Systematic Review and Meta-analysis of Robust Randomised Controlled Studies. European Journal of Vascular and Endovascular Surgery. 2009; 38 (4): 463–474. DOI: https://doi.org/10.1016/j.ejvs.2009.06.002

14. Hood S.C., Moher D., Barber G.G. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. Canadian Medical Association Journal. 1996; 155 (8): 1053–1059.