Clinical trial NCT03159611: Efficacy and Safety Clinical Trial of Tenoten for Children Liquid Dosage Form Therapy in Infants With Sequelae of Perinatal Brain Injury
Official title: Multicenter Double-blind Placebo-controlled Parallel-group Randomized Clinical Trial of Efficacy and Safety of Tenoten for Children Liquid Dosage Form Therapy in Infants With Sequelae of Perinatal Brain Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sequelae of Perinatal Brain Injury
Lead sponsor: Materia Medica Holding
Sponsor class: INDUSTRY
First posted: 2017-05-19
Enrollment: 182
Sex: ALL
Minimum age (years): 29
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Purpose of the study:

* To assess the clinical efficacy of Tenoten for children liquid dosage form therapy (10 oral drops per day for 12 weeks) in Infants with Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischaemia and/or mild-to-moderate intracranial haemorrhage).
* To assess the safety of Tenoten for children liquid dosage form therapy (10 oral drops per day for 12 weeks) in Infants with Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischaemia and/or mild-to-moderate intracranial haemorrhage).


Eligibility criteria: Inclusion Criteria:

1. Full-term infants aged 29 days to 9 months.
2. Diagnosis of Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischemia and/or mild-to-moderate intracranial hemorrhage).
3. Total Jurba-Mastyukova score of \< 27 (but \> 12).
4. Physical development parameters within 25-27 centiles.
5. Neurologist's outpatient observation.
6. Information sheet (informed consent form) for parents/adoptive parents for participation in the clinical study signed by the child's parents/adoptive parents.

Exclusion Criteria:

1. Previously diagnosed lesions, diseases and conditions:

   1.1. Cerebral ischemia (grade III). 1.2. Intraventricular hemorrhage (grade III). 1.3. Metabolic and toxic disorders affecting central nervous system (persistent neonatal hypoglycemia, hyperbilirubinemia associated with elevated indirect bilirubin, and other severe conditions).

   1.4. Intracranial birth injury, focal impairments due to brain injuries (pareses and paralyses).

   1.5. Sequelae of birth injury to spinal cord, cranial nerves and peripheral nervous system (peripheral pareses and paralyses).

   1.6. Different types of hydrocephalus. 1.7. Symptomatic epilepsy and epileptic syndromes. 1.8. Sequelae of perinatal central nervous system (CNS) infectious diseases (injury to CNS caused by neonatal sepsis, encephalitis, meningitis, meningoencephalitis, ventriculitis).

   1.9. Infectious diseases including congenital diseases (cytomegalovirus infection, rubella, herpesvirus or enterovirus infection, toxoplasmosis, syphilis, HIV infection, etc.).

   1.10. Chronic respiratory diseases originating in the perinatal period, including bronchopulmonary dysplasia.

   1.11. Hereditary metabolic diseases including glycogen storage disease (glycogenoses, E74.0), galactose metabolism disorders (galactosemia, Е74.2), other carbohydrate metabolism disorders (Е74), glucosaminoglycan metabolism disorders (mucopolysaccharidoses, Е76), aromatic amino-acid metabolism disorders (phenylketonuria, tyrosinemia, etc, Е70), branched-chain amino-acid and fatty-acid metabolism disorders (maple-syrup-urine disease, Е71), mitochondrial myopathy (G71.3).

   1.12. Neurogenerative diseases including Huntington disease (G10), copper metabolism disorder (Wilson disease, Е83.0).

   1.13. Chromosomal abnormalities. 1.14. Congenital anomalies \[malformations\] and deformities including congenital anomalies of nervous system and malformations of internal organs.

   1.15. Congenital endocrine diseases (congenital hypothyroidism, hypoparathyroidism, adrenocortical dysfunction).

   1.16. Malignant neoplasm / suspected malignant neoplasm.
2. Acute infectious disease, exacerbation / decompensation of diseases that may prevent the patients' participation in the clinical study.
3. Allergy/intolerance of any of the study treatment medications components.
4. Drug addiction, alcohol use in the volume over 2 alcohol units/day by the subject's parent(s)/adoptive parent(s).
5. Mental disorders of the patient's parent(s)/adoptive parent(s).
6. Participation in other clinical studies for a period prior to and during the course of this trial.
7. Other conditions complicating the subject's participation in the study (cannot make regular medical visits, moving, etc.).
8. Subjects whose parent(s)/adoptive parent(s), from the investigator's point of view, will not follow the study requirements or comply with the dosing regimen.
9. Patients whose parent(s)/adoptive parent(s) are related research staff of the clinical investigative site who are directly involved in the study or is a close relative of the investigator. Close relatives include spouse, parents, children or brothers (sisters) regardless of whether they are biological or adoptive ones.
10. Patients whose parent(s)/adoptive parent(s) is working in OOO "NPF "Materia Medica Holding", i.e. is the company official, temporary contract worker or an appointed official responsible for the study or their close relatives.

Primary outcomes:
measure: Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment
timeFrame: in 12 weeks of the treatment
Secondary outcomes:
measure: Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
timeFrame: in 12 weeks of the treatment
measure: Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
timeFrame: in 12 weeks of the treatment
measure: Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
timeFrame: in 12 weeks of the treatment
measure: Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course.
timeFrame: in 12 weeks of the treatment
Other outcomes:
Locations:
city: Ekaterinburg
country: Russian Federation
facility: State Budgetary Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital of Rehabilitation The Scientific and Practical Center "Bonum"
city: Kazan
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University" of the Ministry of Healthcare of the Russian Federation
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First MSMU
city: Moscow
country: Russian Federation
facility: Moscow Regional Research and Clinical Institute ("MONIKI")
city: Perm
country: Russian Federation
facility: Municipal Health Care Institution "City Child Health Clinical Polyclinic №5"
city: Samara
country: Russian Federation
facility: State budgetary institution of public health of the Samara region "Samara City Children's Clinical Hospital No. 1 named after N.N. Ivanova"
city: Saratov
country: Russian Federation
facility: LLC "Center for DNA Research"
city: Tomsk
country: Russian Federation
facility: LLC Nebbiolo
city: Yaroslavl
country: Russian Federation
facility: Federal State Budgetary Educational Institutionof Higher Education "Yaroslavl State Medical University" of the Ministry of Healthcare of the Russian Federation
Study officials:
References: