Trial Outcomes & Findings for Study on Efficacy and Safety of Divaza in Patients With Chronic Cerebral Ischemia and Cognitive Disorders (NCT NCT04370028)

NCT ID: NCT04370028

Last Updated: 2021-03-10

Results Overview

MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome).MoCA test allows to evaluate the presence of cognitive impairment

• Recruitment status: COMPLETED
• Target enrollment: 2583 participants
• Primary outcome timeframe: week 1 to 12 week
• Results posted on: 2021-03-10

Participant Flow

Recruitment period: October 2016 January 2017 Location: outpatient clinics from 8 federal districts of the Russian Federation

Participant milestones

Measure	Divaza Treatment Group All enrolled patients received Divaza 2 tablets 3 times per day for 12 weeks
Overall Study STARTED	2583
Overall Study COMPLETED	1876
Overall Study NOT COMPLETED	707

Reasons for withdrawal

Measure	Divaza Treatment Group All enrolled patients received Divaza 2 tablets 3 times per day for 12 weeks
Overall Study Withdrawal by Subject	695
Overall Study Protocol Violation	9
Overall Study Adverse Event	3

Baseline Characteristics

Age was not reported for 23 patients.

Baseline characteristics by cohort

Measure	Divaza Treatment Group n=1876 Participants All participants received Divaza treatment
Age, Continuous	65.7 years STANDARD_DEVIATION 19.1 • n=1853 Participants • Age was not reported for 23 patients.
Age, Customized Young (<35 yo)	25 participants n=1853 Participants • Age was not reported for 23 patients
Age, Customized Middle aged (35-59 yo)	501 participants n=1853 Participants • Age was not reported for 23 patients
Age, Customized Elderly (60-75 yo)	1062 participants n=1853 Participants • Age was not reported for 23 patients
Age, Customized Senile (75-90 yo)	265 participants n=1853 Participants • Age was not reported for 23 patients
Sex: Female, Male Female	1139 Participants n=1847 Participants • Within each analysis only complete cases approach was used.Sexual identity of 29 patients was not specified.
Sex: Female, Male Male	708 Participants n=1847 Participants • Within each analysis only complete cases approach was used.Sexual identity of 29 patients was not specified.
Baseline MoCA score	19.4 units on a scale STANDARD_DEVIATION 5.1 • n=1855 Participants • Baseline MoCA scores were not reported in 21 patients.

PRIMARY outcome

Timeframe: week 1 to 12 week

Population: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)

MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome).MoCA test allows to evaluate the presence of cognitive impairment

Outcome measures

Measure	Divaza Treatment Group n=1855 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo Senile patients 75-90 yo received Divaza
Mean MoCA Score at Week 1 and the End of the 12-week Therapy 1 week	19.42 score on a scale Standard Deviation 5.13	—	—	—
Mean MoCA Score at Week 1 and the End of the 12-week Therapy 12 week	24 score on a scale Standard Deviation 4.6	—	—	—

SECONDARY outcome

Timeframe: 12 week

Population: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)

The number of patients with mild cognitive impairment. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)

Outcome measures

Measure	Divaza Treatment Group n=1855 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo Senile patients 75-90 yo received Divaza
The Number of Patients With a MoCA Score <26 at 12 Week week 1	1676 participants	—	—	—
The Number of Patients With a MoCA Score <26 at 12 Week week 12	1048 participants	—	—	—

SECONDARY outcome

Timeframe: week1 to week 12

Population: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)

The number of patients with dementia. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)

Outcome measures

Measure	Divaza Treatment Group n=1855 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo Senile patients 75-90 yo received Divaza
The Number of Patients With a MoCA Score ≤ 17 at the End of the 12-week Therapy week 1	489 participants	—	—	—
The Number of Patients With a MoCA Score ≤ 17 at the End of the 12-week Therapy week 12	117 participants	—	—	—

SECONDARY outcome

Timeframe: week1 to week 12

Population: Patients who did not reported age or both MoCA scores were excluded from analysis

Age groups:young <35 yo, middle-aged - 35-59 yo, elderly - 60-75 yo, senile - 75-90 yo MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)

Outcome measures

Measure	Divaza Treatment Group n=25 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo n=501 Participants Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo n=1062 Participants Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo n=265 Participants Senile patients 75-90 yo received Divaza
The Dynamics of Mean MoCA Score in Each Age Group week 1	24 score on a scale Standard Deviation 5.6	20.94 score on a scale Standard Deviation 4.93	19.39 score on a scale Standard Deviation 4.7	16.23 score on a scale Standard Deviation 5.42
The Dynamics of Mean MoCA Score in Each Age Group week 12	26.4 score on a scale Standard Deviation 5.6	25.7 score on a scale Standard Deviation 3.6	23.9 score on a scale Standard Deviation 4.2	20.7 score on a scale Standard Deviation 5.6

SECONDARY outcome

Timeframe: week1 to week 12

Population: Patients who did not reported age or both MoCA scores were excluded from analysis

Age groups:young <35 yo, middle-aged - 35-59 yo, elderly - 60-75 yo, senile - 75-90 yo MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)

Outcome measures

Measure	Divaza Treatment Group n=25 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo n=501 Participants Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo n=1062 Participants Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo n=265 Participants Senile patients 75-90 yo received Divaza
The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups	5 participants	199 participants	616 participants	214 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Data measured at baseline

Population: Patients who did not reported sex or baseline MoCA score were excluded from analysis

Evaluation of the relationship between baseline MoCA test results and gender. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)

Outcome measures

Measure	Divaza Treatment Group n=1139 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo n=708 Participants Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo Senile patients 75-90 yo received Divaza
The Relationship Between Cognitive Impairment and Patients' Gender	19.7 units on a scale Standard Deviation 5.09	18.9 units on a scale Standard Deviation 5.13	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Data measured at baseline

Population: Incomplete data (with respect to used variables) was excluded

Evaluation of the relationship between baseline MoCA test results and regional developmental social or economic indicators (poverty, infant mortality, migration, life expectancy, innovation rate, professional development, number of university students, number of R&D personnel, resources spent on R&D, number of doctors, number of hospitals and outpatient clinics, hospital capacity, fertility rate, quality of life index,income).

Relevance of factors (unitless value) provided. The higher the more influential the factor is.

Relevance was assessed with Boruta approach:

KURSA, Miron B.; RUDNICKI, Witold R.. Feature Selection with the Boruta Package. Journal of Statistical Software, [S.l.], v. 36, Issue 11, p. 1 - 13, sep. 2010. ISSN 1548-7660. Available at: <http://www.jstatsoft.org/v036/i11>. Date accessed: 24 nov. 2020. doi:http://dx.doi.org/10.18637/jss.v036.i11.

Outcome measures

Measure	Divaza Treatment Group n=1797 Participants All analyzed participants received Divaza treatment 2 tablets 3 times per day for 12 weeks	Middle-aged Patients 35-59 yo Middle-aged patients 35-59 yo treated with Divaza	Elderly Patients 60-75 yo Elderly patients 60-75 yo treated with Divaza	Senile Patients 75-90 yo Senile patients 75-90 yo received Divaza
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Hospitals number	5.65 unitless feature importance Interval 5.16 to 6.09	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Nursing personnel	4.69 unitless feature importance Interval 3.87 to 5.63	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Income level	3.83 unitless feature importance Interval 3.0 to 4.59	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors University students	3.79 unitless feature importance Interval 3.19 to 4.33	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Number of doctors	3.78 unitless feature importance Interval 3.17 to 4.19	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors shadowMax (reference zero-importance feature)	2.66 unitless feature importance Interval 1.83 to 3.11	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Age	39.85 unitless feature importance Interval 39.48 to 41.03	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Poverty percentage	8.36 unitless feature importance Interval 7.66 to 8.9	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Infant mortality	7.97 unitless feature importance Interval 7.53 to 8.33	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Migration index	7.92 unitless feature importance Interval 7.23 to 8.42	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Life expectancy	6.42 unitless feature importance Interval 5.86 to 7.15	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Professional development index	6.13 unitless feature importance Interval 5.52 to 6.68	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Number of R&D personnel	5.81 unitless feature importance Interval 4.7 to 6.37	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors R&D expenditures	5.6 unitless feature importance Interval 5.0 to 6.31	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Innovation rate	5.56 unitless feature importance Interval 5.12 to 6.04	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Hospitals capacity	4.89 unitless feature importance Interval 4.46 to 5.16	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Fertility rate	4.87 unitless feature importance Interval 4.3 to 5.41	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors QoL index	4.85 unitless feature importance Interval 4.06 to 5.54	—	—	—
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors Outpatient clinics	4.73 unitless feature importance Interval 4.32 to 5.59	—	—	—

Adverse Events

Divaza Treatment Group

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Divaza Treatment Group n=2583 participants at risk All enrolled patients received Divaza 2 tablets 3 times per day for 12 weeks
Gastrointestinal disorders Nausea	0.12% 3/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Nervous system disorders Dizziness	0.12% 3/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Nervous system disorders Somnolence	0.04% 1/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Nervous system disorders Headache	0.08% 2/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Psychiatric disorders Insomnia	0.04% 1/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Skin and subcutaneous tissue disorders Pruritus	0.08% 2/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Ear and labyrinth disorders Tinnitus	0.04% 1/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Gastrointestinal disorders Dry mouth	0.04% 1/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Skin and subcutaneous tissue disorders Rash pruritic	0.04% 1/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.
Skin and subcutaneous tissue disorders Rash	0.08% 2/2583 • 12 weeks AEs were collected from all patients received a single dose of Divaza according to patient's complaints and physical examination.

Additional Information

Mikhail Putilovskiy, MD, PhD

OOO NPF Materia Medica Holding

Phone: +74952761575

Email: PutilovskiyMA@materiamedica.ru

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place