Treatment of the acute intestinal viral infections in children: results of the international multicenter doubleblind placebo-controlled randomized clinical trial

Abstract

Introduction. Acute intestinal viral infections (AIVI) are one of the leading causes of childhood morbidity. A variety of enteropathogenic viruses and lack of the drugs with multipurpose antiviral activity justify the use of immune-mediated medicines for therapy. The drug Ergoferon is based on antibodies to interferon gamma, CD4, and histamine. The drug enhances regulatory effects of target molecules involved in antiviral immune response.

The aim - to evaluate the effectiveness and safety of Ergoferon in the treatment of AIVI in children aged 6 months to 6 years in an international multicenter double blind placebo-controlled randomized clinical trial (RCT) in parallel groups (phase IV).

Material and methods. RCT enrolled 259 children (from 6 months to 6 years old) hospitalized in the infectious diseases departments of the medical research centers in the Russian Federation and the Republic of Uzbekistan within two days after onset of AIVI. RCT was approved by the Ministry of Healthcare of the Russian Federation, the Ministry of Healthcare of the Republic of Uzbekistan, and national and local ethics councils; RCT was registered in the ClinicalTrials.gov (id: NCT03039699).

Randomization was carried out using interactive voice/web response system in 1:1 ratio. Patients of the testing group (n=127) received Ergoferon according to the dosage scheme for 5 days in addition to the basic therapy of AIVI, patients of the comparison group (n=132) received placebo according to Ergoferon dosage scheme. The average duration of diarrhea was evaluated as a primary endpoint of efficacy. The disease main symptoms duration, the percentage of patients without diarrhea, and the percentage of patients with clinical recovery after 48 and 72 hours from the start of treatment were evaluated as secondary endpoints. Vital signs monitoring, laboratory tests assessment, and adverse events (AEs) recording were used to evaluate therapy safety.

Intention-to-treat (ITT) analysis included 202 patients (n=105, Ergoferon group; n=97, Placebo group); Per Protocol (PP) analysis included 152 patients with verified intestinal viruses (n=81 and n=71, respectively).

Results and discussion. The average duration of diarrhea in Ergoferon group was 43.4±28.2 (43.0±27.3) hours, and it was 11.3±28.3 (14.6±26.5) hours shorter compared to Placebo group [54.7±28.3 (57.6±25.5), p=0.004 (p=0.0009)]. The duration of vomiting period in Ergoferon group was 13.4±28.7 (15.0±25.5) hours shorter [p=0.0044 (p=0.0032)], and disease duration was 12.2±28.3 (14.9±27.2) hours shorter compared to Placebo group [p=0.0039 (p=0.0016)]. The proportions of patients without diarrhea after 48 and 72 hours of treatment in Ergoferon group were 60.2% (60.5%) and 83.5% (85.2%) vs 43.2% (36.6%) [p=0.0675 (p=0.0111)] and 69.5% (67.6%) [p=0.0675 (p=0.0246)] in placebo group; the percentage of children with clinical recovery was 64.1% (63.0%) and 85.4% (86.4%) vs 48.4% (42.3%) [p=0.0696 (p=0.0432)] and 71.6% (70.4%) [p=0.0696 (p=0.0432)], respectively.

Ergoferon was well tolerated by patients; it did not affect vital signs and laboratory tests. The number of patients with AEs did not differ in both groups (p=0.190).

Conclusion. Ergoferon is effective and safe drug for the treatment of AIVI in children aged 6 months to 6 years. Ergoferon add-on to basic therapy significantly reduces diarrhea duration and accelerates the recovery of patients.

Keywords:acute intestinal viral infection, placebo-controlled trial, diarrhea, Ergoferon

Funding. The study was funded by LLC «NPF «Materia Medica Holding» (Moscow, Russia). The study registered in clinicaltrials.gov (NCT03039699). Statistical analysis and current expenses for the processing of article were provided by LLC «NPF «Materia Medica Holding».

Conflict of interest. Ergoferon is produced by LLC «NPF «Materia Medica Holding». Lobzin Yu.V., Gorelov A.V., Usenko D.V., Me-lekhina E.V., Anohin V.A., Samodova O.V., Sabitov A.U., Sitnikov I.G., Timchenko V.N., Musabaev E.I., Loverdo R.G., Koshchav-tseva M.Yu., Pruss V.F., Grekova A.I. were granted from LLC «NPF «Materia Medica Holding» to conduct clinical trial.

The authors of this article confirmed no other conflict of interest, which should be reported.

Contribution. Performing clinical trial in the research centers - Lobzin Yu.V., Gorelov A.V., Usenko D.V., Melekhina E.V., Anokhin V.A., Samodova O.V., Sabitov A.U., Sitnikov I.G., Timchenko V.N., Musabaev E.I., Loverdo R.G., Koshchavtseva M.Yu., Pruss V.F., Grekova A.I.; text writing and editing - Lobzin Yu.V.

For citation: Lobzin Yu.V., Gorelov A.V., Usenko D.V., Melekhina E.V., Anokhin V.A., Samodova O.V., Sabitov A.U., Sitnikov I.G., Timchenko V.N., Musabaev E.I., Loverdo R.G., Koshchavtseva M.Yu., Pruss V.F., Grekova A.I. Treatment of the acute intestinal viral infections in children: results of the international multicenter double-blind placebo-controlled randomized clinical trial. Infektsi-onnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2020; 9 (3): 49-60. DOI: https://doi.org/10.33029/2305-3496-2020-9-3-49-60 (in Russian)

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CHIEF EDITOR
Aleksandr V. Gorelov
Academician of the Russian Academy of Sciences, MD, Head of Infection Diseases and Epidemiology Department of the Scientific and Educational Institute of Clinical Medicine named after N.A. Semashko ofRussian University of Medicine, Ministry of Health of the Russian Federation, Professor of the Department of Childhood Diseases, Clinical Institute of Children's Health named after N.F. Filatov, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Deputy Director for Research, Central Research Institute of Epidemiology, Rospotrebnadzor (Moscow, Russian Federation)

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