Cerebral Atherosclerosis
Conditions
Brief summary
The purpose of this study is to obtain additional data on efficacy and safety of Divaza for adjustment of oxidative disorders in patients with cerebral atherosclerosis. It is assumed that the inclusion of the drug Divaza in the basic therapy will help reduce the severity of cognitive disorders, other clinical symptoms of cerebral atherosclerosis, reduce the impact of the disease on the quality of life of the patient. Participate in the study may be patients with a diagnosis of cerebral atherosclerosis, which, against the backdrop of basic therapy with constant doses of drugs (within the last 4 weeks), to achieve a stable course of cerebral atherosclerosis, cognitive disorders without significant disability are detected.
Detailed description
Design - a multicenter randomized double-blind placebo-controlled parallel-group clinical trial. The study will enroll the patients of either gender aged 40-75 years old inclusively with verified atherosclerotic cerebrovascular lesions (ICD-10 code - Cerebral atherosclerosis \[I67.2\]), with cognitive disorders (МоСА\<26), without relevant incapacity (mRs≤1). At screening visit (Visit 1, from day - 5 to day 0), after signing patient information sheet (informed consent form) for participation in the clinical study the patient's complaints and medical history will be collected and objective examination will be carried out. The investigator will assess intensity of cognitive disorders using MoCA, extent of functional capacity using mRs . If the patient meets inclusion criteria and has no exclusion criteria at Visit 2 (Day 0) he/she will be randomized to one of two groups: group 1 will receive Divaza at 2 tablets 3 times a day; group 2 - placebo using study drug scheme. Laboratory examination will be performed. 1. oxidant and antioxidant systems (Fe2+-induced chemoluminescence method, ELISA) defining: 1.1. level of preformed LP products, predominantly lipid hydroperoxides; 1.2. low and very low density lipoprotein resistance to LP; 1.3. lipoprotein potential for oxidation; 1.4. serum NO product concentration (Griess reaction). 2. compensatory potential of endothelium and its ability for adequate regulation of vascular tone with : 2.1. determination of platelet aggregation with bandage sign; 2.2. MAH duplex scanning. Procedures of Visit 2 may be performed on day of Visit 1 if general rules for blood collection are met, at that previously performed procedures will not be repeated. The first administration of Divaza or Placebo will be performed at Visit 2 at medical site in the investigator's presence. The patient monitoring and therapy will last for 12 weeks during which 3 additional visits will be made. At Visit 3 (Week 4±5 days) the investigator will collect the complaints, perform objective examination, evaluate intensity of cognitive disorders (MoCA). The investigator will monitor the prescribed, basic and concomitant therapy, evaluate therapeutic safety. At Visit 4 (Week 8±5 days) the investigator will make a phone call to the patient to evaluate safety of the treatment. At the final Visit 5 (Weeks 12±5 days) the investigator will evaluate intensity of cognitive disorders (MoCA). Laboratory examination of oxidant and antioxidant systems, compensatory potential of endothelium and its potential for adequate vascular tone regulation. The investigator will monitor the prescribe, basic and concomitant therapy, evaluate therapeutic safety and treatment compliance. During the study basic, concomitant therapy will be allowed except for the products indicated in the section Prohibited concomitant therapy.
Interventions
DRUGDivaza
Oral administration.
DRUGPlacebo
Oral administration.
Sponsors
Materia Medica Holding
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of both genders aged 40-75 years old inclusive. 2. Diagnosis of cerebral atherosclerosis verified by all three signs: * underlying vascular disease (atherosclerosis and/or hypertension) and focal neurological symptoms combined with cerebral symptoms (headache, dizziness, tinnitus, impaired memory, working capacity); * ultrasound signs of atherosclerotic cerebrovascular lesions (according to MAH duplex scanning within 6 months preceding the patient enrollment into the study); * signs of morphological changes in the brain based on neuroimaging (CT/MRI 1.0-1.5 T) (subcortical and periventricular leukoaraiosis and/or focal changes in grey matter and white matter in the form of postischemic cysts and/or lacunar strokes and/or diffuse atrophic changes in the form of dilated cardiovascular system or subarachnoidal spaces). 3. Cognitive disorders (MoCa \<26). 4. Patients with unchanged dose and combination of basic therapy of cerebral atherosclerosis and hypertension during the previous month. 5. Patients who gave their consent to use reliable contraception during the study. 6. Availability of signed patient information sheet and informed consent form for participation in the clinical trial.
Exclusion criteria
1. History of subarachnoidal/parenchymatous/ventricular hemorrhage, cerebral tumour or another disease resulting in neurological disorders. 2. Ischemic-type stroke or any other acute cerebrovascular accident less than 6 months prior to the study with Modified Rankin Scale (mRs) \> 1 . 3. Cardiac sources of high risk or medium risk embolism (TOAST criteria). 4. Signs of acute or exacerbated chronic infectious diseases at or less than 2 weeks prior to screening. 5. History of CNS diseases including: * Inflammatory CNS diseases (G00-G09) * Systemic Atrophies Primarily Affecting the CNS (G10-G13) * Other degenerative diseases of the nervous system (G30-G32) * Demyelinating diseases of the CNS (G35-G37). 6. Dementia (F00-F03). 7. Previously diagnosed cardiovascular diseases with functional class III or IV (according to New York Heart Association, 1964). 8. Hypothyroidism, diabetes mellitus and other somatic diseases at decompensation stage. 9. Uncontrollable hypertension: SBP \> 180 mm Hg and/or DBP \> 110 mm Hg. 10. Diseases of lower limb veins (lower limb varicose veins, deep venous thrombosis, etc.) at decompensation stage. 11. Any other severe concomitant pathology which, according to the investigator, may interfere with the patient's participation in the study. 12. History/suspicion of oncology of any location (except for benign neoplasms). 13. Allergy/intolerance of any component of the drug products used in the therapy. 14. Hereditary lactose intolerance. 15. Malabsorption syndrome, including congenital or acquired lactase deficiency (or any other disaccharidase deficiency) and galactosemia. 16. Pregnancy, breast-feeding. 17. History of treatment non-compliance, psychiatric disorders, alcoholism or drug abuse which, according to the investigator, may interfere with the study procedures. 18. Use of any medicine indicated in the section Prohibited concomitant treatment within 1 month prior to enrollment. 19. Participation in other clinical trials in the previous 3 months. 20. Patients who are related to any of the on-site research personnel directly involved in the study or are an immediate relative of the study investigator, or has another conflict of interests. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted). 21. Patients who work for OOO NPF MATERIA MEDICA HOLDING (i.e. the company's employees, temporary contract workers, appointed officials responsible for carrying out the research or immediate relatives of the aforementioned).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Value of Lipoprotein Resistance to LPO. | 12 weeks of the observation period. | Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Improved Cognitive Function. | 12 weeks of the observation period. | MoCA (Montreal Cognitive Assessment) score +1 and over after 12-week therapy versus baseline. Minimum score is 0, maximum score is 30. Higher values represent a better outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | 12 weeks of the observation period | Based on laboratory evaluation. Change in mean level of preformed LP products, predominantly lipid hydroperoxides after 12-week therapy versus baseline. The following kinetic parameters of chemiluminescence were measured: rapid chemiluminescence flare amplitude reflecting the stationary level of lipid hydroperoxides. |
| Change in Mean Value of Lipoprotein Ability for Oxidation. | 12 weeks of the observation period. | Based on laboratory evaluation. Change in mean value of lipoprotein ability for oxidation after 12-week therapy versus baseline. For plasma, draw blood into an EDTA tube and gently invert the tube 8 to 10 times to mix the anticoagulant. Centrifuge the tube, remove the stopper and draw off approximately 2/3 of the upper plasma layer into a labeled transfer tube using a transfer pipet bulb. Plasma must be separated from cells within 45 minutes of venipuncture. Measurement of oxidized LDL (oxLDL) has been incorporated into clinical practice in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases, especially as it pertains to the evaluation of oxidative stress. Oxidized LDL-particles are considered to be an important driving factor in the pathophysiology of atherosclerosis and oxLDL measurement has been used to test the efficacy of CVD drugs (eg, statins) to reduce oxidative stress. |
| Change in Mean Value of NO Products Serum Concentration. | 12 weeks of the observation period. | Based on laboratory evaluation. Change in the mean concentration of nitrites and nitrates in serum after 12-week therapy versus baseline. Griess Reaction assay. In the Griess reaction, first reported by Johann Peter Griess in 1879 as a method of analysis of nitrite (NO2-), nitrite reacts under acidic conditions with sulfanilic acid (HO3SC6H4NH2) to form a diazonium cation (HO3SC6H4-Ntriple bondN+) which subsequently couples to the aromatic amine 1-naphthylamine (C10H7NH2) to produce a red-violet coloured (λmax ≈ 540 nm), water-soluble azo dye (HO3SC6H4-Ndouble bondN-C10H6NH2). |
| Change in Mean Value of Platelet Aggregation. | 12 weeks of the observation period. | Based on laboratory evaluation. Change in mean platelet aggregation after 12-week therapy versus baseline. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Divaza Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Divaza: Oral administration. | 65 |
| Placebo Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Placebo: Oral administration. | 59 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Non-compliance with inclusion criteria | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Divaza |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 7.4 | 60.7 years STANDARD_DEVIATION 7.6 | 61.4 years STANDARD_DEVIATION 7.8 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Russia | 59 participants | 124 participants | 65 participants |
| Sex: Female, Male Female | 40 Participants | 91 Participants | 51 Participants |
| Sex: Female, Male Male | 19 Participants | 33 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 59 |
| other Total, other adverse events | 5 / 64 | 3 / 59 |
| serious Total, serious adverse events | 0 / 64 | 0 / 59 |
Outcome results
Primary
Change in Mean Value of Lipoprotein Resistance to LPO.
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
Time frame: 12 weeks of the observation period.
Population: 1 patient in Divaza group had no laboratory data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza | Change in Mean Value of Lipoprotein Resistance to LPO. | Resistance of LP to LPO at baseline | 42.4 seconds | Standard Deviation 13.1 |
| Divaza | Change in Mean Value of Lipoprotein Resistance to LPO. | Resistance of LP to LPO after 12 weeks | 55.6 seconds | Standard Deviation 12.5 |
| Divaza | Change in Mean Value of Lipoprotein Resistance to LPO. | ∆ between baseline and after 12 weeks | 14.8 seconds | Standard Deviation 14.7 |
| Placebo | Change in Mean Value of Lipoprotein Resistance to LPO. | Resistance of LP to LPO at baseline | 42.9 seconds | Standard Deviation 11.2 |
| Placebo | Change in Mean Value of Lipoprotein Resistance to LPO. | Resistance of LP to LPO after 12 weeks | 49.4 seconds | Standard Deviation 14.3 |
| Placebo | Change in Mean Value of Lipoprotein Resistance to LPO. | ∆ between baseline and after 12 weeks | 6.4 seconds | Standard Deviation 16.9 |
Comparison: This analysis applies to ∆ between baseline and after 12 weeks row.p-value: 0.007t-test, 2 sided
Secondary
Percentage of Patients With Improved Cognitive Function.
MoCA (Montreal Cognitive Assessment) score +1 and over after 12-week therapy versus baseline. Minimum score is 0, maximum score is 30. Higher values represent a better outcome.
Time frame: 12 weeks of the observation period.
Population: 8 patients in Divaza group and 2 patients in Placebo group had no data for week 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Divaza | Percentage of Patients With Improved Cognitive Function. | 56 Participants |
| Placebo | Percentage of Patients With Improved Cognitive Function. | 51 Participants |
p-value: 0.0272Fisher Exact
Other Pre-specified
Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides).
Based on laboratory evaluation. Change in mean level of preformed LP products, predominantly lipid hydroperoxides after 12-week therapy versus baseline. The following kinetic parameters of chemiluminescence were measured: rapid chemiluminescence flare amplitude reflecting the stationary level of lipid hydroperoxides.
Time frame: 12 weeks of the observation period
Population: 1 patient in Divaza group had no laboratory data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza | Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | Level of preformed LPO products at baseline | 72.5 Mcmol / L | Standard Deviation 14.1 |
| Divaza | Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | Level of preformed LPO products after 12 weeks | 67.7 Mcmol / L | Standard Deviation 13.1 |
| Divaza | Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | ∆ between baseline and after 12 weeks | -3.2 Mcmol / L | Standard Deviation 9.6 |
| Placebo | Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | Level of preformed LPO products at baseline | 72.8 Mcmol / L | Standard Deviation 12.9 |
| Placebo | Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | Level of preformed LPO products after 12 weeks | 69.9 Mcmol / L | Standard Deviation 11.7 |
| Placebo | Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides). | ∆ between baseline and after 12 weeks | -2.9 Mcmol / L | Standard Deviation 8 |
Comparison: This analysis applies to ∆ between baseline and after 12 weeks row.p-value: 0.8762t-test, 2 sided
Other Pre-specified
Change in Mean Value of Lipoprotein Ability for Oxidation.
Based on laboratory evaluation. Change in mean value of lipoprotein ability for oxidation after 12-week therapy versus baseline. For plasma, draw blood into an EDTA tube and gently invert the tube 8 to 10 times to mix the anticoagulant. Centrifuge the tube, remove the stopper and draw off approximately 2/3 of the upper plasma layer into a labeled transfer tube using a transfer pipet bulb. Plasma must be separated from cells within 45 minutes of venipuncture. Measurement of oxidized LDL (oxLDL) has been incorporated into clinical practice in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases, especially as it pertains to the evaluation of oxidative stress. Oxidized LDL-particles are considered to be an important driving factor in the pathophysiology of atherosclerosis and oxLDL measurement has been used to test the efficacy of CVD drugs (eg, statins) to reduce oxidative stress.
Time frame: 12 weeks of the observation period.
Population: 1 patient in Divaza group had no laboratory data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza | Change in Mean Value of Lipoprotein Ability for Oxidation. | ∆ between baseline and after 12 weeks | -12.1 mV | Standard Deviation 192.1 |
| Divaza | Change in Mean Value of Lipoprotein Ability for Oxidation. | LP ability for oxidation at baseline | 1027.3 mV | Standard Deviation 204.7 |
| Divaza | Change in Mean Value of Lipoprotein Ability for Oxidation. | LP ability for oxidation after 12 weeks | 1024.1 mV | Standard Deviation 226.7 |
| Placebo | Change in Mean Value of Lipoprotein Ability for Oxidation. | LP ability for oxidation at baseline | 993.8 mV | Standard Deviation 264.1 |
| Placebo | Change in Mean Value of Lipoprotein Ability for Oxidation. | ∆ between baseline and after 12 weeks | 57.0 mV | Standard Deviation 241.5 |
| Placebo | Change in Mean Value of Lipoprotein Ability for Oxidation. | LP ability for oxidation after 12 weeks | 1040.6 mV | Standard Deviation 217.7 |
Comparison: This analysis applies to ∆ between baseline and after 12 weeks row.p-value: 0.2082Wilcoxon (Mann-Whitney)
Other Pre-specified
Change in Mean Value of NO Products Serum Concentration.
Based on laboratory evaluation. Change in the mean concentration of nitrites and nitrates in serum after 12-week therapy versus baseline. Griess Reaction assay. In the Griess reaction, first reported by Johann Peter Griess in 1879 as a method of analysis of nitrite (NO2-), nitrite reacts under acidic conditions with sulfanilic acid (HO3SC6H4NH2) to form a diazonium cation (HO3SC6H4-Ntriple bondN+) which subsequently couples to the aromatic amine 1-naphthylamine (C10H7NH2) to produce a red-violet coloured (λmax ≈ 540 nm), water-soluble azo dye (HO3SC6H4-Ndouble bondN-C10H6NH2).
Time frame: 12 weeks of the observation period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO level after 12 | 7.8 μmol per liter | Standard Deviation 3.9 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-3 level (after cuff test) at baseline | 38.4 μmol per liter | Standard Deviation 16.5 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-3 level (after cuff test) after 12 weeks | 64.0 μmol per liter | Standard Deviation 15.6 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-2 level at baseline | 35.9 μmol per liter | Standard Deviation 16 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-2 level after 12 weeks | 43.9 μmol per liter | Standard Deviation 22.2 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-2 level (after cuff test) after 12 weeks | 57.0 μmol per liter | Standard Deviation 14.5 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO level at baseline | 5.4 μmol per liter | Standard Deviation 2.3 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO level (after cuff test) at baseline | 6.6 μmol per liter | Standard Deviation 1.8 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO level (after cuff test) after 12 weeks | 7.0 μmol per liter | Standard Deviation 2.8 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-3 level after 12 weeks | 51.7 μmol per liter | Standard Deviation 23.9 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-2 level (after cuff test) at baseline | 31.8 μmol per liter | Standard Deviation 16.1 |
| Divaza | Change in Mean Value of NO Products Serum Concentration. | NO-3 level at baseline | 41.3 μmol per liter | Standard Deviation 14.9 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO level after 12 | 10.7 μmol per liter | Standard Deviation 4.5 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-3 level at baseline | 69.0 μmol per liter | Standard Deviation 28.9 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-2 level (after cuff test) after 12 weeks | 51.0 μmol per liter | Standard Deviation 25.9 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-3 level (after cuff test) at baseline | 79.1 μmol per liter | Standard Deviation 33.5 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-3 level after 12 weeks | 63.3 μmol per liter | Standard Deviation 36.8 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO level at baseline | 6.3 μmol per liter | Standard Deviation 4.1 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-3 level (after cuff test) after 12 weeks | 61.1 μmol per liter | Standard Deviation 27.9 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO level (after cuff test) after 12 weeks | 10.1 μmol per liter | Standard Deviation 5.2 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-2 level at baseline | 62.8 μmol per liter | Standard Deviation 28 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-2 level (after cuff test) at baseline | 69.6 μmol per liter | Standard Deviation 32.3 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO level (after cuff test) at baseline | 9.5 μmol per liter | Standard Deviation 4 |
| Placebo | Change in Mean Value of NO Products Serum Concentration. | NO-2 level after 12 weeks | 52.5 μmol per liter | Standard Deviation 35.9 |
Comparison: This analysis applies to NO-3 data.p-value: 0.0038Mixed Models Analysis
Comparison: This analysis applies to NO-2 data.p-value: 0.0018Mixed Models Analysis
Comparison: This analysis applies to NO data.p-value: 0.46Mixed Models Analysis
Other Pre-specified
Change in Mean Value of Platelet Aggregation.
Based on laboratory evaluation. Change in mean platelet aggregation after 12-week therapy versus baseline.
Time frame: 12 weeks of the observation period.
Population: ADP-AP - platelet aggregation (PA) induced by adenosine diphosphate (ADP) ADR-AP - platelet aggregation (PA) induced by adrenaline (ADR)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza | Change in Mean Value of Platelet Aggregation. | ADR-PA at baseline | 48.4 percentage aggregation | Standard Deviation 12.2 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADP-PA (after cuff test) after 12 weeks | 49.7 percentage aggregation | Standard Deviation 14.6 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADR-PA (after cuff test) at baseline | 44.7 percentage aggregation | Standard Deviation 13.3 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADP-PA (after cuff test) at baseline | 45.0 percentage aggregation | Standard Deviation 14 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADR-PA after 12 weeks | 47.7 percentage aggregation | Standard Deviation 11.8 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADP-PA at baseline | 46.9 percentage aggregation | Standard Deviation 13.8 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADR-PA (after cuff test) after 12 weeks | 54.1 percentage aggregation | Standard Deviation 8.6 |
| Divaza | Change in Mean Value of Platelet Aggregation. | ADP-PA after 12 weeks | 45.3 percentage aggregation | Standard Deviation 12.5 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADR-PA (after cuff test) after 12 weeks | 57.4 percentage aggregation | Standard Deviation 14.6 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADP-PA (after cuff test) after 12 weeks | 52.5 percentage aggregation | Standard Deviation 11.6 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADP-PA at baseline | 44.6 percentage aggregation | Standard Deviation 14.1 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADP-PA (after cuff test) at baseline | 51.9 percentage aggregation | Standard Deviation 15.7 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADR-PA at baseline | 47.8 percentage aggregation | Standard Deviation 16.4 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADR-PA (after cuff test) at baseline | 53.1 percentage aggregation | Standard Deviation 16.8 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADR-PA after 12 weeks | 51.4 percentage aggregation | Standard Deviation 11.3 |
| Placebo | Change in Mean Value of Platelet Aggregation. | ADP-PA after 12 weeks | 46.3 percentage aggregation | Standard Deviation 9.4 |
Comparison: This analysis applies to ADP-PA data.p-value: 0.88Mixed Models Analysis
Comparison: This analysis applies to ADR-PA data.p-value: 0.93Mixed Models Analysis