Edaravone-Sodium Ozagrel Comparative Post-Marketing Study on Acute Ischemic Stroke

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00200356
• Collaborator: (none)
• Enrollment: 401
• Arms: 2
• Duration (Months): 26

Study Details

Study Description

Brief Summary

This study is randomized, Sodium Ozagrel (Thromboxane A2 Synthase Inhibitor) controlled study on acute ischemic stroke. The primary endpoints were the rate of patients with modified Rankin Scale score of 0-1 at 3 months.

Condition or Disease	Intervention/Treatment	Phase
Cerebral Infarction	Drug: Edaravone; Drug: Sodium Ozagrel	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 401 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Edaravone-Sodium Ozagrel (Thromboxane A2 Synthase Inhibitor) Comparative Post-Marketing Study on Acute Ischemic Stroke
• Study Start Date: Aug 1, 2004
• Actual Study Completion Date: Oct 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Edaravone	Drug: Edaravone; Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.; Other Names: Radicut
Active Comparator: Ozagrel	Drug: Sodium Ozagrel; Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.

Outcome Measures

Primary Outcome Measures

1. the Rate of Patients With a Modified Rankin Scale Score of 0-1 [3 months]

   The number of patients with mRS score of 0-1 (good outcome) at 3 months after treatment initiation. The mRS has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability.

Secondary Outcome Measures

1. Barthel Index Score [3 months]

   The Barthel Index of Activities of Daily Living measures functional disability by quantifying patient performance in 10 activities of daily life. These activities can be grouped according to self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers, and stair climbing). 5-point increments are used in scoring, with a maximal score of 100 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state. The number of patients with 95-100 Barthel Index was evaluated at at 3 months after treatment initiation.

2. Baseline NIH Stroke Scale Score [Before treatment initiation]

   The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead).

3. NIH Stroke Scale Score at 14 Days [14 days]

   The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead). The number of patients with NIH stroke scale score of 0-1 at 14 days after treatment initiation.

4. NIH Stroke Scale Score at 1 Month [1 month]

   The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead). The number of patients with NIH stroke scale score of 0-1 at 1 month after treatment initiation.

5. NIH Stroke Scale Score at 3 Months [3 months]

   The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead). The number of patients with NIH stroke scale score of 0-1 at 3 months after treatment initiation.

6. Japan Stroke Scale (Motor Function) Score at 14 Days [14 days]

   The Japan stroke scale (motor function) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from -0.26 (no deficit) to 31.29 (worst). The mean of Japan stroke scale (motor function) score at 14 days after treatment initiation.

7. Japan Stroke Scale (Motor Function) Score at 1 Month [1 month]

   The Japan stroke scale (motor function) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from -0.26 (no deficit) to 31.29 (worst). The mean of Japan stroke scale (motor function) score at 1 month after treatment initiation.

8. Japan Stroke Scale (Motor Function) Score at 3 Months [3 months]

   The Japan stroke scale (motor function) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from -0.26 (no deficit) to 31.29 (worst). The mean of Japan stroke scale (motor function) score at 3 months after treatment initiation.

9. Modified Rankin Scale Score [6 months]

   The number of patients with an Modified Rankin Scale score of 0-1 was evaluated at 6 months after treatment initiation. The Modified Rankin Scale has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients can be receive drug treatment within 24 hours after stroke onset

2. Patients with a level of consciousness between 0 (alert) and 3 (unable to recall name and date of birth) according to the Japan Coma Scale

3. Patients with motor dysfunction of upper and/or lower extremities

4. Patients aged 20 years or older when giving informed consent

Exclusion Criteria:

1. Serum creatinine of >1.5 mg/dL

2. Embolic infarction

3. Intracranial haemorrhage

4. Large infarction with severe consciousness

5. Transient ischemic attack (TIA)

6. A modified Rankin Scale score of ≥2 before stroke onset

7. Patients were receive drug treatment (argatroban, urokinase, tissue plasminogen activator, heparin, warfarin sodium, aspirin, ticlopidine hydrochloride, cilostazol, edaravone and sodium ozagrel) after stroke onset

8. Patients were receive surgical treatment or intravascular treatment

9. With severe complications (cirrhosis, heart failure, etc.)

10. Treating malignant tumor

11. Pregnant or possibly pregnant women, nursing mothers

12. History of edaravone, sodium ozagrel and ozagrel hydrochloride sensitivity

13. Less than 3 months since any other clinical trial or postmarketing study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Chair: Yukito Shinohara, MD, Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00200356
• Other Study ID Numbers: MCI186-13
• First Posted: Sep 20, 2005
• Last Update Posted: Jan 15, 2013
• Last Verified: Dec 1, 2012

• Additional relevant MeSH terms: Ischemic Stroke; Cerebral Infarction; Infarction; Ozagrel; Edaravone

Study Results

Participant Flow

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Period Title: Overall Study
STARTED	199	202
Safety Analysis Set	194	198
COMPLETED	191	195
NOT COMPLETED	8	7

Baseline Characteristics

Arm/Group Title	Edaravone	Ozagrel	Total
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.	Total of all reporting groups
Overall Participants	191	195	386
Age, Customized (years) [Number]
birth-19 years	0	0	0
20-64 years	64	58	122
65- years	127	137	264
Sex: Female, Male (Count of Participants)
Female	70 36.6%	77 39.5%	147 38.1%
Male	121 63.4%	118 60.5%	239 61.9%

Outcome Measures

1. Secondary Outcome

Title	Barthel Index Score
Description	The Barthel Index of Activities of Daily Living measures functional disability by quantifying patient performance in 10 activities of daily life. These activities can be grouped according to self-care (feeding, grooming, bathing, dressing, bowel and bladder care, and toilet use) and mobility (ambulation, transfers, and stair climbing). 5-point increments are used in scoring, with a maximal score of 100 indicating that a patient is fully independent in physical functioning, and a lowest score of 0 representing a totally dependent bed-ridden state. The number of patients with 95-100 Barthel Index was evaluated at at 3 months after treatment initiation.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	191	195
Number [participants]	148 77.5%	133 68.2%

2. Secondary Outcome

Title	Baseline NIH Stroke Scale Score
Description	The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead).
Time Frame	Before treatment initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	191	195
Mean (Standard Deviation) [scores on a scale]	3.7 (2.3)	3.8 (2.7)

3. Secondary Outcome

Title	NIH Stroke Scale Score at 14 Days
Description	The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead). The number of patients with NIH stroke scale score of 0-1 at 14 days after treatment initiation.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	190	193
Number [participants]	98 51.3%	108 55.4%

4. Secondary Outcome

Title	NIH Stroke Scale Score at 1 Month
Description	The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead). The number of patients with NIH stroke scale score of 0-1 at 1 month after treatment initiation.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	190	195
Number [participants]	117 61.3%	119 61%

5. Primary Outcome

Title	the Rate of Patients With a Modified Rankin Scale Score of 0-1
Description	The number of patients with mRS score of 0-1 (good outcome) at 3 months after treatment initiation. The mRS has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	191	195
Score(0-1)	109 57.1%	98 50.3%
0	46 24.1%	39 20%
1	63 33%	59 30.3%
2	37 19.4%	40 20.5%
3	22 11.5%	29 14.9%
4	19 9.9%	24 12.3%
5	2 1%	3 1.5%
Death	2 1%	1 0.5%

6. Secondary Outcome

Title	NIH Stroke Scale Score at 3 Months
Description	The NIH stroke scale is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42(dead). The number of patients with NIH stroke scale score of 0-1 at 3 months after treatment initiation.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	191	195
Number [participants]	135 70.7%	140 71.8%

7. Secondary Outcome

Title	Japan Stroke Scale (Motor Function) Score at 14 Days
Description	The Japan stroke scale (motor function) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from -0.26 (no deficit) to 31.29 (worst). The mean of Japan stroke scale (motor function) score at 14 days after treatment initiation.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	190	193
Mean (Standard Deviation) [units on a scale]	4.521 (6.651)	4.686 (6.872)

8. Secondary Outcome

Title	Japan Stroke Scale (Motor Function) Score at 1 Month
Description	The Japan stroke scale (motor function) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from -0.26 (no deficit) to 31.29 (worst). The mean of Japan stroke scale (motor function) score at 1 month after treatment initiation.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	190	195
Mean (Standard Deviation) [units on a scale]	3.632 (6.086)	3.680 (5.885)

9. Secondary Outcome

Title	Japan Stroke Scale (Motor Function) Score at 3 Months
Description	The Japan stroke scale (motor function) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from -0.26 (no deficit) to 31.29 (worst). The mean of Japan stroke scale (motor function) score at 3 months after treatment initiation.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	189	194
Mean (Standard Deviation) [units on a scale]	2.507 (5.232)	2.927 (5.361)

10. Secondary Outcome

Title	Modified Rankin Scale Score
Description	The number of patients with an Modified Rankin Scale score of 0-1 was evaluated at 6 months after treatment initiation. The Modified Rankin Scale has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Edaravone	Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.	Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
Measure Participants	186	193
Number [participants]	112 58.6%	108 55.4%

Adverse Events

Arm/Group Title	Edaravone		Ozagrel
Arm/Group Description	Edaravone, at 30 mg, is intravenously administered by drip over 30 minutes b.i.d., in the morning and the evening.		Sodium Ozagrel, at 80 mg, is intravenously administered by drip over 2 hours b.i.d., in the morning and the evening.
All Cause Mortality
	Edaravone		Ozagrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Edaravone		Ozagrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/194 (13.9%)		28/198 (14.1%)
Cardiac disorders
Angina pectoris	1/194 (0.5%)		0/198 (0%)
Arrhythmia	1/194 (0.5%)		0/198 (0%)
Cardiac failure	0/194 (0%)		1/198 (0.5%)
Ear and labyrinth disorders
Vertigo	1/194 (0.5%)		0/198 (0%)
Gastrointestinal disorders
Constipation	0/194 (0%)		1/198 (0.5%)
Duodenal ulcer	1/194 (0.5%)		0/198 (0%)
Duodenal ulcer haemorrhage	1/194 (0.5%)		0/198 (0%)
Ileus	2/194 (1%)		0/198 (0%)
Inguinal hernia	1/194 (0.5%)		0/198 (0%)
Vomiting	0/194 (0%)		1/198 (0.5%)
Hepatobiliary disorders
Liver disorder	0/194 (0%)		1/198 (0.5%)
Immune system disorders
Anti-neutrophil cytoplasmic antibody positive vasculitis	1/194 (0.5%)		0/198 (0%)
Infections and infestations
Erysipelas	0/194 (0%)		1/198 (0.5%)
Pharyngitis	0/194 (0%)		1/198 (0.5%)
Pneumonia	2/194 (1%)		1/198 (0.5%)
Urinary tract infection	1/194 (0.5%)		1/198 (0.5%)
Injury, poisoning and procedural complications
Anastomotic ulcer haemorrhage	1/194 (0.5%)		0/198 (0%)
Brain herniation	0/194 (0%)		1/198 (0.5%)
Femoral neck fracture	1/194 (0.5%)		0/198 (0%)
Femur fracture	1/194 (0.5%)		0/198 (0%)
Pelvic fracture	1/194 (0.5%)		0/198 (0%)
Spinal compression fracture	0/194 (0%)		1/198 (0.5%)
Upper limb fracture	0/194 (0%)		1/198 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/194 (0%)		1/198 (0.5%)
Lymphoma	1/194 (0.5%)		0/198 (0%)
Nervous system disorders
Carpal tunnel syndrome	0/194 (0%)		1/198 (0.5%)
Cerebral haemorrhage	1/194 (0.5%)		0/198 (0%)
Cerebral infarction	5/194 (2.6%)		11/198 (5.6%)
Haemorrhagic cerebral infarction	0/194 (0%)		1/198 (0.5%)
Hemiplegia	0/194 (0%)		2/198 (1%)
Loss of consciousness	0/194 (0%)		1/198 (0.5%)
Sciatica	0/194 (0%)		1/198 (0.5%)
Thrombotic stroke	1/194 (0.5%)		0/198 (0%)
Transient ischemic attack	2/194 (1%)		0/198 (0%)
Psychiatric disorders
Depression	1/194 (0.5%)		0/198 (0%)
Psychotic disorder due to a general medical condition	1/194 (0.5%)		0/198 (0%)
Renal and urinary disorders
Renal failure acute	0/194 (0%)		1/198 (0.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/194 (0.5%)		0/198 (0%)
Pneumonia aspiration	0/194 (0%)		1/198 (0.5%)
Pulmonary embolism	0/194 (0%)		1/198 (0.5%)
Vascular disorders
Arteriosclerosis	0/194 (0%)		1/198 (0.5%)
Shock haemorrhagic	0/194 (0%)		1/198 (0.5%)
Other (Not Including Serious) Adverse Events
	Edaravone		Ozagrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	102/194 (52.6%)		107/198 (54%)
Gastrointestinal disorders
Constipation	59/194 (30.4%)		64/198 (32.3%)
Diarrhea	10/194 (5.2%)		6/198 (3%)
Infections and infestations
Nasopharyngitis	19/194 (9.8%)		13/198 (6.6%)
Urinary tract infection	9/194 (4.6%)		11/198 (5.6%)
Musculoskeletal and connective tissue disorders
Back pain	11/194 (5.7%)		17/198 (8.6%)
Nervous system disorders
Headache	11/194 (5.7%)		12/198 (6.1%)
Psychiatric disorders
Insomnia	24/194 (12.4%)		33/198 (16.7%)
Skin and subcutaneous tissue disorders
Pruritus	9/194 (4.6%)		10/198 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.