Efficacy and safety of a drug based on regulatory polypeptides of vessels for treatment of intermittent claudication (results of a multicenter, double-blind, placebo-controlled randomized trial)

• Igor А. Suchkov
• Kalinin R.E.
• Mzhavanadze N.D.
• Kamaev A.A.
• Burenin A.G.
• Larkov R.N.

Abstract

Objective. To evaluate efficacy and safety of various dosage regimens of Slavinorm^® compared with placebo in patients with stage IIB chronic obliterating diseases of lower-limb arteries according to the Fontaine-Pokrovsky classification.

Patients and methods. The study was planned as a multicenter (7 centers), double-blind, placebo-controlled, comparative trial in parallel groups. It included a total of 108 patients with confirmed atherosclerotic lesions of lower-limb arteries and symptoms of intermittent claudication. The diagnosis was verified by duplex scanning of vessels, treadmill test, and the ankle-brachial index.

The overall duration of participation in the study for each patient was not more than 91 days, with the period of drug administration ranging from 22 to 33 days.

The patients were randomized into one of four treatment groups:

Group A (n=36): patients received the studied drug Slavinorm^® intramuscularly at a dose of 5 mg two times a week.

Group B (n=36): patients received the studied drug Slavinorm^® intramuscularly at a dose of 5 mg three times a week.

Group C (n=18): patients received placebo intramuscularly twice a week.

Group D (n=18); patients received placebo intramuscularly three times a week.

Each patient during the study received 10 doses of the drug or placebo.

Slavonirm^® is a complex of polypeptides derived from vessels of cattle. The technology of production of the drug envisages that the finished dosage form should contain only polypeptides having molecular weights not exceeding 10 kDa, with complete absence of proteins, lipids, hormones and pyrogens.

The main criterion for efficacy was the proportion of patients demonstrating a therapeutic response at the time of the final visit as a 50% and more increase in the pain-free walking distance as compared with the baseline level. Additional criteria for efficacy assessment were the average alteration in the maximal pain-free walking distance and maximal walking distance at various stages of treatment, change in the total score of the Walking Impairment Questionnaire (WIQ) at various stages of treatment, general assessment of efficacy of treatment, made by the patient/investigator at various visits, frequency of taking analgesics to relieve pain, the number of patients withdrawing from the study for the reason of ineffective treatment.

The measures to assess safety included changes in physical and laboratory parameters, as well as the frequency of unfavorable and adverse events.

The groups of patients formed according to the study design were comparable by the main parameters.

Results. Using Slavinorm^® turned out to result in a statistically significant increase in the pain-free walking distance (by 46.2 and 31.4% in Groups A and B, respectively) as compared with the placebo group (+6.5%). A 50% increase in the pain-free walking distance was observed in 28 and 26% of patients in the Slavinorm^® Groups as compared with 3% of patients in the placebo group. The use of Slavinorm^® improved the assessment by the patients of their general condition, walking distance and speed according to the WIQ scale. According to the general assessment of treatment efficacy, 95.7% of patients and 94.2% of investigators noted improvement of the patients’ state on the background of therapy with Slavinorm^®. The frequency of adverse events in the Slavinorm group did not statistically significantly differ from the placebo group (p=0.55983). The effect of the drug persisted after discontinuation of the drug administration (9–25 days after the last injection of Slavinorm).

Conclusion. Slavinorm^® used according to the dosage regimens A (at a dose of 5 mg twice weekly, 10 injections) and B (at a dose of 5 mg thrice weekly, 10 injections) possesses clinical efficacy and increases the pain-free walking distance in patients with stage IIB chronic obliterating disease of lower-limb arteries according to the Fontaine–Pokrovsky classification.

Slavinorm^® has a favorable safety profile, with the frequency of adverse events not differing statistically significantly from the placebo group.

Keywords:chronic obliterating diseases of lower-limb arteries; intermittent claudication; pain-free walking; clinical trial; peptides; Slavinorm®; regulatory polypeptides of vessels

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