A phase II trial was conducted to evaluate the safety, tolerability and efficacy of sovateltide, an endothelin B receptor agonist, in patients with acute cerebral ischemic stroke. |
Sovateltide was administered in three doses, each 0.3 μg/kg, as an intravenous bolus over 1 min at an interval of 3 ± 1 h on day 1, day 3 and day 6 (total dose/day: 0.9 µg/kg) post randomization. |
Sovateltide was safe and well-tolerated. No adverse events were reported. |
Significantly more patients in the sovateltide group had an improved Barthel Index (BI) score of ≥ 40 points at 90 days of follow up (64 vs. 36% in the control group). |
The number of patients showing a favorable improvement in modified Rankin Scale (mRS) (change of ≥ 2 points vs. baseline) and National Institute of Health Stroke Scale (NIHSS) (change of ≥ 6 points vs. baseline) at 90 days was numerically but not statistically significantly greater (at a 95% confidence level) in the sovateltide group (60 vs. 40% in the control group; 56 vs. 43% in the control group, respectively). |
The sovateltide group had significantly more patients with an NIHSS score of 0 and a BI score of 100, indicating that sovateltide increased the frequency of complete recovery compared with patients in the control group. The sovateltide group also had more patients with an mRS score of 0, although this was not statistically significant. |
1 Introduction
2 Methods
2.1 Patients, Eligibility Criteria and Trial Design
2.2 Treatment Regimen
2.3 Data Safety Monitoring Board
2.4 Safety and Tolerability Assessments
2.5 Assessment of Neurological Outcome
2.6 Blinding/Unblinding
2.7 Sample Size and Statistical Methods
3 Results
3.1 Demographics and Patient Characteristics
Site no. | Study site | Total enrolled |
---|---|---|
1 | NewEra Hospital, Near Jalaram Mandir, Queta Colony, Telephone Exchange Chowk, Central Avenue Road, Nagpur 440008 Maharashtra | 12 |
2 | Christian Medical College and Hospital, Department of Neurology, Brown Road, Ludhiana -141008 Punjab | 02 |
3 | All India Institute of Medical Sciences, Department of Neurology, Neurosciences Centre, Ansari Nagar, New Delhi - 110029 | 08 |
4 | Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Neurology, Ground Floor, Raebareli Road, Lucknow - 226014 Uttar Pradesh | 05 |
5 | Paras Hospital, C-1, Sushant Lok-1, Sector-43, Gurgaon 122002, Haryana | 01 |
6 | Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana, 141001 Punjab | 10 |
7 | Nizam's Institute of Medical Sciences. Punjagutta, Hyderabad 500082, Telangana | 02 |
Group | Sex | Age (years) | Body weight (kg) | Height (cm) | BMI (kg/m2) |
---|---|---|---|---|---|
Normal saline (N = 18) | 11M/7F | 58.34 ± 1.73 | 64.97 ± 2.40 | 163.72 ± 2.08 | 24.47 ± 0.98 |
Sovateltide (N = 18) | 15M/3F | 49.83 ± 2.79 | 67.82 ± 2.47 | 168.78 ± 1.50 | 24.00 ± 0.68 |
Standard treatment + saline (N = 18) | Standard treatment + sovateltide (N = 18) | ||||
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Subject no. | Case details | Scores at admission | Subject no. | Case details | Scores at admission |
01-001 | Male, age 65 years; heaviness, tingling and numbness in head; unconscious; drowsy; one seizure; red blood spot in right eye Medical history: HTN, T2DM Cardiovascular: BP 170/80 mmHg; pulse 80 bpm. ECG: sinus rhythm; LVH with strain pattern. Echo: mild aortic stenosis, LVH, grade II diastolic dysfunction CT/MRI: CT scan showed small subtle area of hypodensity in left lentiform nucleus suggestive of acute non-hemorrhagic infarct. Chronic vessel ischemic changes in right peri-ventricular white matter | NIHSS 5; mRS 3 | 01-002 | Male, age 68 years; slurred speech; right side mouth deviation; left-side weakness since morning; power in left upper and lower limbs grade IV; grip weak Medical history: None Cardiovascular: BP 140/90 mmHg; pulse 83 bpm. ECG: sinus rhythm, right bundle branch block. Echo: mild ventricular hypertrophy, mild stenosis aortic valve, mild mitral regurgitation, LVEF 65% CT/MRI: CT scan showed acute to subacute infarct (patchy hypodensities) involving right gangliocapsular region and right temporal lobe | NIHSS 6; mRS 4 |
01-004 | Female, age 56 years; weakness in right upper and lower limb since morning; slurred speech; decreased oral intake; nausea; right hemiplegia Medical history: HTN, T2DM Cardiovascular: BP 160/90 mmHg; pulse 60 bpm. ECG: sinus rhythm, LVH with strain pattern. Echo: LVEF 65% CT/MRI: CT scan showed multiple small patchy acute to subacute infarct involving left gangliocapsular region, corona radiata centrum semiovale | NIHSS 7; mRS 4 | 01-003 | Male, age 55 years; right-side weakness with upper and lower limb; right-side hemiparesis; power in right upper and lower limbs grade III+ Medical history: HTN Cardiovascular: BP 120/80 mmHg; pulse 80 bpm. ECG: sinus rhythm, LVH CT/MRI: CT scan showed patchy areas of small hypodensities involving bilateral gangliocapsular region, left thalamus, left corona radiata, acute to subacute infarct | NIHSS 5; mRS 4 |
01-005 | Male, age 51 years; left-side weakness; slurred speech; mouth deviation; left hemiparesis Medical history: Systemic HTN, T2DM Cardiovascular: BP 150/100 mmHg; pulse 84 bpm CT/MRI: CT scan showed small hypodensities involving right caudate nucleus suggesting acute to sub-acute infarct. Diffuse cerebral atrophy. MRI of brain and neck with angiography showed early subacute right MCA territory infarct involving right fronto-parietal, temporal and gangliocapsular region, hemorrhagic transformation in the right gangliocapsular region and frontal lobe. Mass on the right lateral ventricle with midline shift towards left of about 2 mm. Chronic lacunar infarct in the inferior aspect of left cerebellum. Loss of flow-related signal in the M1, M2 and M3 segments of right MCA, suggestive of complete occlusion | NIHSS 13; mRS 4 | 01-006 | Male, age 48 years; right-side body weakness; mouth deviation; slurred speech for 1 day Medical history: None Cardiovascular: BP 150/100 mmHg; pulse 80 bpm. Echo: congenital heart disease. Small 3 mm restrictive ventricular septal defect with left to right shunt; LVEF 65% CT/MRI: CT scan showed tiny hypodensities involving left side of medulla and left insular cortex | NIHSS 6; mRS 3 |
01-008 | Female, age 53 years; heaviness in left side of body and head; headache; imbalance while walking and standing for 1 day before admission; left-side hemiparesis; grip weak; power in left upper limb grade III, left lower limb grade IV Medical history: T2DM Cardiovascular: BP 180/110 mmHg; pulse 84 bpm CT/MRI: CT scan showed small infarct bilateral thalamus, left corona radiata and pons on right sides | NIHSS 5; mRS 3 | 01-007 | Male, age 58 years; right-sided weakness; numbness upper limb and slurring speech for 2 h before admission; right hemiparesis; power in right upper and lower limbs grade III, grip weak Medical history: None Cardiovascular: BP 200/120 mmHg; pulse 72 bpm; Echo: Concentric LVH; LVEF 65%; grade I diastolic dysfunction of the left ventricle, mild sclerosis aortic valve CT/MRI: CT scan showed subtle hypodensity in left occipital region, infarct. Old lacunar infarcts in bilateral ganglioncapsular region and mild age-related diffuse cerebral atrophy | NIHSS 6; mRS 4 |
01-009 | Male, age 64 years; uneasiness; eight episodes of nausea with vomiting; numbness of right upper and lower limb with weakness; slurring of speech; deviation of mouth towards left side for 1 h before admission; power grade IV on right side; right side grip weak Medical history: None Cardiovascular: BP 140/80 mmHg; pulse 76 bpm. ECG: sinus rhythm, left axis deviation Echo: LVEF 60%, grade I diastolic dysfunction of the left ventricle CT/MRI: CT scan showed small subtle hypodensity in left parietal region suggestive of infarct | NIHSS 7; mRS 3 | 01-010 | Male, age 40 years; slurred speech; tingling, numbness and weakness of right upper limb since morning; power in right upper limb grade IV; grip weak Medical history: None Cardiovascular: BP 120/80 mmHg; pulse 86 bpm CT/MRI: CT scan showed tiny calcification with surrounding hypodensity and edema in left parietal lobe | NIHSS 6; mRS 3 |
01-012 | Female, age 47 years; vomiting; vertigo; bed wet since 2 days before admission; right-sided weakness and aphasia since morning; right hemiparesis Medical history: T2DM Cardiovascular: BP 200/110 mmHg; pulse 76 bpm CT/MRI: CT scan showed areas of hypodensity in left temporal region. MRI showed acute non-hemorrhagic left ACA territory infarct in left parafalcine frontal lobe and left half of the body of corpus callosum | NIHSS 8; mRS 4 | 01-011 | Male, age 30 years; left-side weakness and slurring of speech since morning; left hemiparesis; left upper limb weakness; power in left upper and lower limb grade III Medical history: None Cardiovascular: BP 150/90 mmHg; pulse 103 bpm. Echo: coronary artery disease; moderate to severe LVEF 35%; mild mitral regurgitation; grade I diastolic dysfunction of the left ventricle CT/MRI: MRI showed bilateral intracranial ICA and MCA; atherosclerotic wall thickening with significant narrowing of right distal M1, M2, with non-visualization of distal M2, M3 and M4 segments showing occlusion. Screening of brain revealed area of altered signal intensity in right parieto-temporal region appearing hyperintense on T2/FLAIR and restricted diffusion on diffusion-weighted imaging suggesting acute infarct | NIHSS 8; mRS 3 |
03-001 | Female, age 47 years; left-side body weakness; slurring of speech and facial deviation to left since morning; power in left upper and lower limbs 0/5; left hemianesthesia. Cranial nerve: gaze preference to right; left facial upper motor neuron palsy Medical history: Hypothyroidism and dyslipidemia for 4 years Cardiovascular: BP 146/60 mmHg; pulse 70 bpm CT/MRI: CT scan showed acute right MCA infarct (large). CT angiography showed right ICA complete occlusion | NIHSS 19; mRS 4 | 02-001 | Male, age 55 years; right upper limb weakness; dysarthria; sensory loss of right upper and lower limbs; power in upper and lower limbs 4/5 Medical history: None Cardiovascular: BP 150/90 mmHg; pulse 90 bpm. Echo: LVEF 55% CT/MRI: MRI showed acute thalamic non-hemorrhagic infarct; high-grade stenosis/occlusion of left posterior cerebral artery (P2) and focal segmental stenosis of right posterior cerebral artery | NIHSS 13; mRS 4 |
03-003 | Male, age 61 years; sudden-onset right-side upper and lower limb weakness; slurred speech and facial deviation to left; right upper and lower limb hypotonia; power in right upper and lower limbs 4/5. Cranial nerve: right upper motor neuron facial palsy. Gait: dragging of right leg while walking Medical history: T2DM, HTN Cardiovascular: BP 110/80 mmHg; pulse 88 bpm CT/MRI: CT scan showed hypodensity in left internal capsule. CT angiography showed no major vessel occlusion | NIHSS 6; mRS 4 | 02-002 | Male, age 53 years; weakness in left upper limb and deviation of mouth right side for 14 h before admission; power in left upper limb 2/5 and left lower limb 3/5. Cranial nerve: left upper motor neuron facial palsy Medical history: DM, HTN Cardiovascular: BP 140/80 mmHg; pulse 68 bpm. ECG: Minor left axis deviation CT/MRI: CT scan showed abrupt cutoff at M1, M2 segment of right MCA suggestive of thrombotic occlusion. Focal filling defect in right common carotid artery, suggestive of atheromatic lipid-rich plaques. MRI showed right-side fronto-parietal internal watershed infarct along with areas of restricted diffusion along the parieto-occipital cortical region | NIHSS 12; mRS 4 |
03-006 | Female, age 66 years; acute-onset weakness of right upper and lower limb; mild facial deviation to left side; right hemiparesis; power in right upper and lower limbs 4/5; mild dysarthria. Cranial nerves: mild right upper motor neuron facial weakness Medical history: None Cardiovascular: BP 70/100 mmHg; pulse 70 bpm CT/MRI: CT scan showed left MCA territory infarct. CT angiography showed left posterior cerebral artery and generalized intracranial atherosclerotic changes | NIHSS 5; mRS 4 | 03-004 | Male, age 61 years; acute-onset weakness of right upper and lower limb; slurred speech; deviation of mouth to left side. Cranial nerve: left hemianopia present Medical history: None Cardiovascular: BP 170/100 mmHg; pulse 80 bpm. Echo: LVEF 60% CT/MRI: CT scan showed left MCA territory infarct, ASPECTS 6/10, left internal capsule, putamen, insula, M6. CT angiography showed partial occlusion at left MCA bifurcation | NIHSS 11; mRS 4 |
03-008 | Male, age 62 years; weakness of right upper and lower limbs with deviation of angle of mouth and slurring of speech since morning Medical history: None Cardiovascular: BP 136/80 mmHg; pulse 86 bpm. ECG: ST depression in VI-6, L II-L III CT/MRI: CT scan showed ASPECTS 9/10. Hypodensity in left MCA territory in left corona radiata extending to lentiform nucleus. CT angiography showed no major vessel occlusion | NIHSS 12; mRS 4 | 03-005 | Male, age 58 years; acute-onset weakness of left upper and lower limbs; visual difficulty; slurred speech; power in left upper limb 3+/5 and left lower limb 4/5; left hemianopia Medical history: T2DM, HTN. Ischemic heart disease and CABG in 2014. Gangrene and self-amputation of left big toe 7 years previously; acute quadriparesis 35 years previously Cardiovascular: BP 150/90 mmHg; pulse 80 bpm. ECG: left bundle branch block. Normal sinus rhythm. Echo: moderate left systolic dysfunction. Regional wall motion abnormalities in posterolateral septum. LVEF 35–40% CT/MRI: CT scan showed infarct in right internal capsule, ASPECTS 9/10. CT angiography showed 60% stenosis of left ICA | NIHSS 7; mRS 4 |
04-002 | Male, age 54 years; acute-onset weakness of right face, arm and leg; slurred speech; right hemiplegia Medical history: HTN and T2DM. Left hemiparesis 1 year previously, recovered completely Cardiovascular: BP 140/90 mmHg; pulse 90 bpm CT/MRI: CT scan showed left internal capsule ischemic stroke | NIHSS 13; mRS 4 | 03-007 | Male, age 58 years; right-sided weakness; mild deviation in mouth to left side since morning Medical history: HTN Cardiovascular: BP 140/94 mmHg, pulse 68 bpm. Echo: Mild LVH. Normal LV function (EF 60%) CT/MRI: CT scan showed subtle hypodensity in right putamen. CT angiography showed mild paucity of flow in one distal branch of left MCA | NIHSS 6; mRS 4 |
04-003 | Female, age 62 years; right-sided face, arm, leg weakness since morning; slurred speech since previous night. Deep tendon reflexes: brisk on right vs. left. Grade 2 in lower limb, grade 1 in upper limb; no sensory deficit. Right-sided hemiparesis Medical history: Hypothyroid and T2DM. CAD and right hemiparesis 12 years previously Cardiovascular: BP 160/90 mmHg; pulse 56 bpm CT/MRI: CT scan showed left fronto-parietal infarct | NIHSS 13; mRS 4 | 04-001 | Male, age 60 years; acute-onset left upper and lower arm weakness with altered sensorium; irritable and restless; left hemiplegia Medical history: None Cardiovascular: BP 140/90 mmHg; pulse 90 bpm. Carotid doppler suggestive of >90% stenosis in right ICA CT/MRI: CT scan showed ill-defined hypodensity in right MCA territory | NIHSS 14; mRS 4 |
04-005 | Male, age 69 years; left-side facial deviation; slurred speech; power in right upper and lower limbs >3/5; left upper and lower limbs 0/5 Medical history: T2DM for 12 years Cardiovascular: BP 130/80 mmHg; pulse 76 bpm CT/MRI: MRI showed right MCA infarct | NIHSS 11; mRS 4 | 04-004 | Female, age 32 years; tingling and paresthesia in right upper and lower limbs with hemi-cranial headache; weakness in left upper and lower limbs; facial deviation. Weakness initially mild but worsened over 5 h to cause complete loss of power in left upper and lower limbs. Vomiting, seizures, visual complaints, speech abnormality, urinary incontinence, cough, chest pain, palpitations. Left upper motor neuron facial palsy Medical history: Balloon mitral valvulotomy in 2009 Cardiovascular: BP 110/62 mmHg; pulse 90 bpm. CVS: S1 loud; ejection systolic murmur noted in pulmonary artery CT/MRI: CT scan showed subacute infarct in right basal ganglia region. MRI showed acute infarct in right caudate nucleus, right putamen. Insular cortex, subtle blooming noted in SWAN. Chronic infarct in right posterior cerebellum | NIHSS 11; mRS 4 |
06-002 | Male, age 64 years; restless and right-side weakness for 1 day; right arm weakness and slurred speech for 2 days of admission Medical history: None Cardiovascular: BP 130/80 mmHg; pulse 86 bpm. Echo: Normal LV size and systolic function; LVEF 60% CT/MRI: MRI showed multifocal acute infarcts fronto-parieto-occipital region involving left insular cortex, likely embolic | NIHSS 11; mRS 4 | 06-001 | Male, age 44 years; left-side weakness, left hemiparesis associated with facial abnormality on right side; heaviness of speech; patient could not recognize people, completely empty urinary bladder, or clench teeth; drooled food from left side from angle of mouth; decreased wrinkles, closing of eyelids and nasolabial fold on left side; power in left upper and lower limbs 1/5 Medical history: None Cardiovascular: BP 110/70 mmHg; pulse 70 bpm; ECG: Right bundle branch block CT/MRI: MRI showed right MCA infarct | NIHSS 16; mRS 4 |
06-006 | Male, age 56 years; slurred speech; left-side facial deviation with facial nerve palsy since morning Medical history: T2DM for 3 years Cardiovascular: BP 120/70 mmHg; pulse 72 bpm. Carotid doppler: 20% plaque at left carotid bulb CT/MRI: MRI showed small acute infarct in right internal capsule | NIHSS 8; mRS 3 | 06-004 | Male, age 57 years; vomiting and slurred speech 1 day before admission; multiple episodes of vomiting; facial deviation Medical history: None Cardiovascular: BP 130/80 mmHg; pulse 80 bpm. Echo: LVEF 60% CT/MRI: Area of altered signal intensity appearing hyperintense on T2/FLAIR and showing DR on DW/ADC involving right cerebellar hemisphere; B/L tonsils suggestive of acute infarct. Multiple areas showing diffuse restriction in the rest of B/L cerebellar hemispheres and pons suggestive of acute infarcts. Few T2/FLAIR hyperintense foci without DR in B/L corona radiata and centrum semiovale; chronic ischemic changes. Normal CT angiography | NIHSS 14; mRS 4 |
06-007 | Female, age 50 years; slurred speech; weakness of right upper and lower limb for 1 day before admission; right upper motor neuron facial nerve palsy; power in right limbs grade 4/5; power in left limbs grade 5/5 Medical history: None Cardiovascular: BP 180/100 mmHg; pulse 96 bpm. ECG: Suspected LVH CT/MRI: MRI showed multifocal infarct in left MCA territory with no mass effect | NIHSS 9; mRS 4 | 06-005 | Male, age 30 years; left-side weakness; slurred speech with facial deviation towards right side since morning; power in left upper and lower limbs 0/5; left 7th upper motoneuron palsy Medical history: None Cardiovascular: BP 120/70 mmHg; pulse 78 bpm CT/MRI: CT scan showed large right territory infarct; CT angiography showed right ICA attenuated | NIHSS 13; mRS 4 |
06-009 | Male, age 70 years; right-side weakness; right hemiparesis; memory loss; power in right lower limb 4/5 Medical history: HTN for 2 years Cardiovascular: BP 160/90 mmHg; pulse 76 bpm. Echo: Mild concentric LVH. LVEF 60% CT/MRI: MRI showed multiple acute infarct in posterior cerebral artery territory | NIHSS 7; mRS 4 | 06-008 | Male, age 54 years; altered sensorium; speech arrest; drooling of saliva associated with bowel incontinence 3–4 h before admission; left eye ptosis. Tone increased in left limbs; deep tendon reflexes 1+ in all four limbs Medical history: DM, HTN. Cerebrovascular accident – right thalamic infarct, left hemiparesis with residual weakness and facial nerve nucleus lesion Cardiovascular: BP 170/80 mmHg; pulse 74 bpm. ECG: LVH. Echo: LVEF 60% CT/MRI: MRI showed acute infarct in left MCA territory; no evidence of hemorrhagic transformation | NIHSS 16; mRS 4 |
07-002 | Male, age 53 years; slurred speech; word finding difficulty; weakness of right upper limb; deviation of mouth to left side. Cranial nerve: VII, mild facial palsy Medical history: HTN; alcoholic Cardiovascular: BP 180/100 mmHg; pulse 76 bpm. Color doppler: arthero-scleromatous changes in left carotids; plaques in right common carotid artery, left distal common carotid artery CT/MRI: MRI showed acute infarct in left parietal and frontal lobe. Narrowing of M2 and M3 segment with paucity of cortical branches on right side | NIHSS 6; mRS 3 | 07-001 | Female, age 33 years; sudden-onset slurred speech and deviation of angle of mouth to right side since morning; facial dysarthria; tongue deviation to right side Medical history: None Cardiovascular: BP 110/70 mmHg; pulse 82 bpm CT/MRI: MRI showed hypodensity in right pre-central gyrus suggesting subacute infarct | NIHSS 5; mRS 3 |
Pt no. | SOC + saline (N = 18) | Pt no. | SOC + sovateltide (N = 18) |
---|---|---|---|
01-001 | Enoxaparin injection, aspirin tablet, rosuvastatin tablet, cilnidipine and chlorthalidone tablet | 01-002 | Enoxaparin injection, rosuvastatin tablet, amlodipine tablet, aspirin and clopidogrel tablet |
01-004 | Enoxaparin injection, aspirin tablet, clopidogrel and rosuvastatin tablet | 01-003 | Amlodipine tablet, enoxaparin injection, cognistar injection, aspirin tablet, clopidogrel, telmisartan tablet, rosuvastatin tablet |
01-005 | Cognistar injection, levetiracetam tablet, mannitol injection, rosuvastatin tablet, amlodipine tablet, aspirin tablet, furosemide tablet, rosuvastatin tablet | 01-006 | Enoxaparin injection, aspirin and clopidogrel tablet, amlodipine tablet |
01-008 | Enoxaparin injection, aspirin and clopidogrel tablet, rosuvastatin tablet | 01-007 | Enoxaparin injection, aspirin and clopidogrel tablet, rosuvastatin tablet, cognistar injection, labetalol tablet, amlodipine tablet, nifedipine tablet |
01-009 | Aspirin and clopidogrel tablet, atorvastatin tablet, cognistar injection | 01-010 | Enoxaparin injection, aspirin and clopidogrel tablet, mannitol injection |
01-012 | Enoxaparin injection, cognistar injection, aspirin and clopidogrel tablet, rosuvastatin tablet, amlodipine tablet | 01-011 | Atorvastatin tablet, enoxaparin injection, cognistar injection, nicoumalone tablet |
03-001 | Mannitol, aspirin tablet, amlodipine tablet, atorvastatin tablet | 02-001 | Alteplase injection, aspirin tablet, atorvastatin tablet, escitalopram tablet, telmisartan tablet |
03-003 | Aspirin tablet, atorvastatin tablet | 02-002 | Heparin injection, aspirin tablet, atorvastatin tablet, enoxaparin injection |
03-006 | Amlodipine tablet, aspirin tablet, clopidogrel tablet, atorvastatin tablet | 03-004 | Amlodipine tablet, alteplase, aspirin tablet, atorvastatin tablet |
03-008 | Amlodipine tablet, tenecteplase, aspirin tablet, atorvastatin tablet | 03-005 | Metoprolol tablet, aspirin tablet, clopidogrel tablet, ramipril tablet, atorvastatin tablet |
04-002 | Aspirin and atorvastatin capsule | 03-007 | Atorvastatin tablet, aspirin tablet, clopidogrel tablet, fluoxetine tablet, amlodipine tablet |
04-003 | Aspirin and atorvastatin capsule, clopidogrel tablet | 04-001 | Aspirin and atorvastatin capsule |
04-005 | Atorvastatin tablet, aspirin tablet, telmisartan tablet, clopidogrel tablet | 04-004 | Nicoumalone tablet, furosemide and spironolactone tablet, enoxaparin injection |
06-002 | Aspirin and clopidogrel tablet, mannitol injection, atorvastatin tablet, dalteparin injection | 06-001 | Aspirin tablet, clopidogrel tablet, atorvastatin tablet, trimetazidine tablet |
06-006 | Aspirin tablet, atorvastatin tablet, telmisartan and amlodipine tablet | 06-004 | Aspirin tablet, atorvastatin tablet |
06-007 | Aspirin tablet, atorvastatin tablet, amlodipine tablet, telmisartan tablet, fluoxetine capsule | 06-005 | Aspirin tablet, mannitol injection, enoxaparin injection, furosemide injection, atorvastatin tablet |
06-009 | Telmisartan and amlodipine tablet, aspirin, atorvastatin and clopidogrel tablet, memantine tablet | 06-008 | Olmesartan and amlodipine tablet, atorvastatin tablet, phenytoin syrup, aspirin and clopidogrel tablet |
07-002 | Aspirin tablet, atorvastatin tablet | 07-001 | Aspirin tablet, atorvastatin tablet |