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| ID | Type | Description | Link |
|---|---|---|---|
| ISRCTN47341677 | Registry Identifier | ISRCTN registry |
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| Name | Class |
|---|---|
| FDA Office of Orphan Products Development | FED |
| Genentech, Inc. | INDUSTRY |
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The specific objective of this trial is to determine the lowest dose and dose frequency possible with the best pharmacokinetic and safety profile and it's ability to remove a blood clot from the ventricular system.
The purpose of this trial is to determine the efficacy and pharmacokinetics of intraventricular injections of multiple low doses of rt-PA. Sixteen subjects were already randomized to receive intraventricular injections of with 0.3 mg or 1.0 mg of rt-PA every 12 hours for up to 8 doses. Results of this stage (n=16) were then analyzed and the most effective dose of 1.0 mg was chosen to be used in the second stage (n=36) to determine the optimal frequency of dosing. We propose to test if this intervention facilitates more rapid clot resolution, complete recovery function and decreased mortality from this condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.3 mg rt-PA | Active Comparator | In stage 1 of the protocol, dose finding, subjects were randomized to either this 0.3 mg dose arm or the 1.0 mg dose arm. Subjects in this arm (0.3 mg) received up to 8 doses of 0.3 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage. |
|
| 1.0 mg rt-PA | Active Comparator | In stage 1 of the protocol, dose finding, subjects were randomized to either this 1.0 mg dose arm or the 0.3 mg dose arm. Subjects in this arm (1.0 mg) received up to 8 doses of 1.0 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage. |
|
| 1.0 mg Rt-PA q8h | Experimental | In stage 2 of the protocol, dose frequency, subjects received up to 8 doses of 1.0 mg of rt-PA (Cathflo) every 8 hours through the intraventricular catheter to treat intraventricular hemorrhage. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo) | Drug | 0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage. |
| Measure | Description | Time Frame |
|---|---|---|
| 30-day Mortality | The number of subjects who died at or before the 30-day follow-up visit were determined as a measure of safety. If more than 50% of the subjects died at or before the 30-day follow-up visit, the study would have been stopped for full DSMB review. | 30 days |
| Incidence of Bacterial Ventriculitis, Meningitis | The incidence of bacterial ventriculitis/meningitis was recorded to determine the safety of intraventricular administration of rt-PA. If 30% or more subjects experienced this event, the study would have been stopped for full DSMB review. | 30 days |
| Rate of Symptomatic Bleeding Events | The rate of symptomatic brain bleeding events were recorded to determine the safety of intraventricular administrations of rt-PA. If 35% or more subjects experienced a symptomatic bleeding event prior to the 30-day follow-up visit, the study would have been stopped for a full DSMB review. | 30-days |
| Measure | Description | Time Frame |
|---|---|---|
| Average Daily Percentage Clot Size Resolution Over the First 3 Days | Daily IVH clot volume resolution, as a percentage of stability CT IVH volume, averaged over the first 3 days, determined by CT scans | 3 days |
| 90 Day Follow-Up Modified Rankin Scale (mRS) Score |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel F Hanley, MD | Johns Hopkins University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| CR Drew Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26228884 | Derived | Kornbluth J, Nekoovaght-Tak S, Ullman N, Carhuapoma JR, Hanley DF, Ziai W. Early Quantification of Hematoma Hounsfield Units on Noncontrast CT in Acute Intraventricular Hemorrhage Predicts Ventricular Clearance after Intraventricular Thrombolysis. AJNR Am J Neuroradiol. 2015 Sep;36(9):1609-15. doi: 10.3174/ajnr.A4393. Epub 2015 Jul 30. | |
| 23463422 |
| Label | URL |
|---|---|
| CLEAR III Website | View source |
Not provided
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Recruitment began for protocol stage 1 in August 2005 and ended for protocol stage 2 on February 6, 2008. Subjects were screened by clinical stroke service personnel in the Emergency Department or by direct transfer from an outside hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.3 mg Rt-PA q12h | Stage 1 (Dose Finding) |
| FG001 | 1.0 mg Rt-PA q12h | Stage 1 (Dose Finding) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
90 day follow-up visit mRS score. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) |
| 90 days |
| 90 Day Follow-Up Glasgow Outcome Scale (GOS) Score | 90 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | 90 days |
| 180 Day Follow-Up Modified Rankin Scale (mRS) Score | 180 day follow-up visit mRS score. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | 180 days |
| 180 Day Follow-Up Glasgow Outcome Scale (GOS) Score | 180 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | 180 days |
| Los Angeles |
| California |
| 90059 |
| United States |
| Standford Medical Center | Palo Alto | California | 94394 | United States |
| Hartford Hospital | Hartford | Connecticut | 06102 | United States |
| Loyola University Medical Center | Maywood | Illinois | 60153 | United States |
| Via Christi Regional Medical Center | Wichita | Kansas | 67214 | United States |
| University of Maryland Medical Systems | Baltimore | Maryland | 21202 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| St. Louis University | St Louis | Missouri | 63110 | United States |
| Albany Medical Center | Albany | New York | 12208 | United States |
| Mt. Sinai Medical Center | New York | New York | 10029 | United States |
| University of Cincinnati | Cincinnati | Ohio | 45267 | United States |
| Temple University | Philadelphia | Pennsylvania | 19140 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| University of Texas HSC, San Antonio | San Antonio | Texas | 78229 | United States |
| University of Virginia, Charlottesville | Charlottesville | Virginia | 22908 | United States |
| INOVA Fairfax Medical Center | Fairfax | Virginia | 22042 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Foothills Medical Centre | Calgary | Alberta | T2N 2T9 | Canada |
| University of Heidelberg | Heidelberg | 69120 | Germany |
| Newcastle General Hospital | Newcastle upon Tyne | NE4 6BE | United Kingdom |
| Ziai W, Moullaali T, Nekoovaght-Tak S, Ullman N, Brooks JS, Morgan TC, Hanley DF. No exacerbation of perihematomal edema with intraventricular tissue plasminogen activator in patients with spontaneous intraventricular hemorrhage. Neurocrit Care. 2013 Jun;18(3):354-61. doi: 10.1007/s12028-013-9826-1. |
| 23370203 | Derived | Morgan TC, Dawson J, Spengler D, Lees KR, Aldrich C, Mishra NK, Lane K, Quinn TJ, Diener-West M, Weir CJ, Higgins P, Rafferty M, Kinsley K, Ziai W, Awad I, Walters MR, Hanley D; CLEAR and VISTA Investigators. The Modified Graeb Score: an enhanced tool for intraventricular hemorrhage measurement and prediction of functional outcome. Stroke. 2013 Mar;44(3):635-41. doi: 10.1161/STROKEAHA.112.670653. Epub 2013 Jan 31. |
| 22474059 | Derived | Webb AJ, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF. Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke. 2012 Jun;43(6):1666-8. doi: 10.1161/STROKEAHA.112.650523. Epub 2012 Apr 3. |
| 22382155 | Derived | Ziai WC, Muschelli J, Thompson CB, Keyl PM, Lane K, Shao S, Hanley DF. Factors affecting clot lysis rates in patients with spontaneous intraventricular hemorrhage. Stroke. 2012 May;43(5):1234-9. doi: 10.1161/STROKEAHA.111.641050. Epub 2012 Mar 1. |
| 21940973 | Derived | Herrick DB, Ziai WC, Thompson CB, Lane K, McBee NA, Hanley DF. Systemic hematologic status following intraventricular recombinant tissue-type plasminogen activator for intraventricular hemorrhage: the CLEAR IVH Study Group. Stroke. 2011 Dec;42(12):3631-3. doi: 10.1161/STROKEAHA.111.625749. Epub 2011 Sep 22. |
| FG002 |
| 1.0 mg Rt-PA q8h |
Stage 2 (Dose Optimization) |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 0.3 mg Rt-PA q12h | Stage 1 (Dose Finding) |
| BG001 | 1.0 mg Rt-PA q12h | Stage 1 (Dose Finding) |
| BG002 | 1.0 mg Rt-PA q8h | Stage 2 (Dose Optimization) |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 30-day Mortality | The number of subjects who died at or before the 30-day follow-up visit were determined as a measure of safety. If more than 50% of the subjects died at or before the 30-day follow-up visit, the study would have been stopped for full DSMB review. | Posted | Number | Number of participants | 30 days |
|
|
| |||||||||||||||||||||||||||||||||
| Primary | Incidence of Bacterial Ventriculitis, Meningitis | The incidence of bacterial ventriculitis/meningitis was recorded to determine the safety of intraventricular administration of rt-PA. If 30% or more subjects experienced this event, the study would have been stopped for full DSMB review. | Posted | Number | Number of participants | 30 days |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Rate of Symptomatic Bleeding Events | The rate of symptomatic brain bleeding events were recorded to determine the safety of intraventricular administrations of rt-PA. If 35% or more subjects experienced a symptomatic bleeding event prior to the 30-day follow-up visit, the study would have been stopped for a full DSMB review. | Posted | Number | participants | 30-days |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Average Daily Percentage Clot Size Resolution Over the First 3 Days | Daily IVH clot volume resolution, as a percentage of stability CT IVH volume, averaged over the first 3 days, determined by CT scans | Posted | Mean | Full Range | Percent of stability CT volume resolved | 3 days |
|
| |||||||||||||||||||||||||||||||||
| Secondary | 90 Day Follow-Up Modified Rankin Scale (mRS) Score | 90 day follow-up visit mRS score. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | Posted | Median | Full Range | mRS score | 90 days |
|
| |||||||||||||||||||||||||||||||||
| Secondary | 90 Day Follow-Up Glasgow Outcome Scale (GOS) Score | 90 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | Posted | Median | Full Range | GOS score | 90 days |
|
| |||||||||||||||||||||||||||||||||
| Secondary | 180 Day Follow-Up Modified Rankin Scale (mRS) Score | 180 day follow-up visit mRS score. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | Posted | Median | Full Range | mRS score | 180 days |
|
| |||||||||||||||||||||||||||||||||
| Secondary | 180 Day Follow-Up Glasgow Outcome Scale (GOS) Score | 180 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected) | Posted | Median | Full Range | GOS score | 180 days |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.3 mg Rt-PA q12h | Stage 1 (Dose Finding) | 3 | 8 | 7 | 8 | ||
| EG001 | 1.0 mg Rt-PA q12h | Stage 1 (Dose Finding) | 2 | 8 | 8 | 8 | ||
| EG002 | 1.0 mg Rt-PA q8h | Stage 2 (Dose Optimization) | 11 | 36 | 32 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accidental Extubation | Respiratory, thoracic and mediastinal disorders |
| |||
| Cardiac Arrest | Cardiac disorders |
| |||
| Cerebral Infarction | Nervous system disorders |
| |||
| Hemorrhage new catheter tract >5 mm with mass effect, symptomatic | Nervous system disorders |
| |||
| Hydrocephalus, Communicating | Nervous system disorders |
| |||
| ICH Hemorrhage, new symptomatic | Nervous system disorders |
| |||
| IVH Hemorrhage enlargement - asymptomatic | Nervous system disorders |
| |||
| IVH Hemorrhage enlargement - symptomatic | Nervous system disorders |
| |||
| IVH hemorrhage, new symptomatic | Nervous system disorders |
| |||
| Myocardial Infarction | Cardiac disorders |
| |||
| Seizure | Nervous system disorders |
| |||
| Suspected cardiac or pulmonary embolism | Respiratory, thoracic and mediastinal disorders |
| |||
| Tracheal stricture | Respiratory, thoracic and mediastinal disorders |
| |||
| Ventilatory failure, mechanical | Respiratory, thoracic and mediastinal disorders |
| |||
| Ventriculitis, Bacterial | Nervous system disorders |
| |||
| Ventriculitis, non-bacterial | Nervous system disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Renal Failure | Renal and urinary disorders |
| |||
| Adult Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders |
| |||
| Anemia | Blood and lymphatic system disorders |
| |||
| Aspiration | Respiratory, thoracic and mediastinal disorders |
| |||
| Atelectasis | Respiratory, thoracic and mediastinal disorders |
| |||
| Atrial Fibrillation | Cardiac disorders |
| |||
| Bacteremia | Blood and lymphatic system disorders |
| |||
| Bradycardia | Cardiac disorders |
| |||
| Brain Edema / Swelling | Nervous system disorders |
| |||
| CSF Leak | Nervous system disorders |
| |||
| Cerebral Infarction | Nervous system disorders |
| |||
| Cerebral infarction, extension | Nervous system disorders |
| |||
| Congestive Heart Failure | Cardiac disorders |
| |||
| Decreased Level of counciousness | Nervous system disorders |
| |||
| Decubitus ulcer | Skin and subcutaneous tissue disorders |
| |||
| Diarrhea | Renal and urinary disorders |
| |||
| Edema (metabolic causes) | Metabolism and nutrition disorders |
| |||
| Encephalopathy | Nervous system disorders |
| |||
| Fever of unknown origin | General disorders |
| |||
| Headache | Nervous system disorders |
| |||
| Hemorrhage enl, cath tract >5mm w/o mass, asym | Nervous system disorders |
| |||
| Hemorrhage enlargement, catheter tract > 5 mm with mass effect, asymptomatic | Nervous system disorders |
| |||
| Hemorrhage, new catheter tract <= 5 mm, asymptomatic | Nervous system disorders |
| |||
| Hemorrhage, new catheter tract > 5 mm with mass effect, asymptomatic | Nervous system disorders |
| |||
| Hemorrhage, new catheter tract > 5 mm with mass effect, symptomatic | Nervous system disorders |
| |||
| Herniation, Brain | Nervous system disorders |
| |||
| Hydrocephalus, Obstructive | Nervous system disorders |
| |||
| Hydrocephalus, communicating | Nervous system disorders |
| |||
| Hyperglycemia | Blood and lymphatic system disorders |
| |||
| Hypertension | Cardiac disorders |
| |||
| Hypokalemia | Blood and lymphatic system disorders |
| |||
| Hyponatremia | Blood and lymphatic system disorders |
| |||
| Hypoxemia | Blood and lymphatic system disorders |
| |||
| ICH hemorrhage enlargement, asymptomatic | Nervous system disorders |
| |||
| ICH hemorrhage, new asymptomatic | Nervous system disorders |
| |||
| ICH hemorrhage, new symptomatic | Nervous system disorders |
| |||
| IVH hemorrhage enlargement - asymptomatic | Nervous system disorders |
| |||
| Increased Blood Urea Nitrogen | Blood and lymphatic system disorders |
| |||
| Increased midline shift | Nervous system disorders |
| |||
| Intracranial hypertension | Nervous system disorders |
| |||
| Peri-hemorrhagic ischemic change | Nervous system disorders |
| |||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders |
| |||
| Pneumonia | Respiratory, thoracic and mediastinal disorders |
| |||
| Pneumonia, aspiration | Respiratory, thoracic and mediastinal disorders |
| |||
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders |
| |||
| SAH Hemorrhage, new asymptomatic | Nervous system disorders |
| |||
| Siezure | Nervous system disorders |
| |||
| Sinus tachycardia | Cardiac disorders |
| |||
| Skin Exanthema | Infections and infestations |
| |||
| Tracheitis | Respiratory, thoracic and mediastinal disorders |
| |||
| Urinary tract infection | Renal and urinary disorders |
| |||
| Ventilatory failure | Respiratory, thoracic and mediastinal disorders |
| |||
| Ventriculitis, bacterial | Nervous system disorders |
| |||
| Ventriculitis, non-bacterial | Nervous system disorders |
|
The PI shall provide the sponsor with a copy of any proposed publication for review and comment thirty (30) days prior to submission. JHU may request a delay in publication, not to exceed 90 days if it is necessary to protect any intellectual property.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniel F. Hanley, MD | Johns Hopkins University | 410-614-6996 | dhanley@jhmi.edu |
| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| D005343 | Fibrinolytic Agents |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
| D050299 | Fibrin Modulating Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D006401 | Hematologic Agents |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
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| Canada |
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| Germany |
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| United Kingdom |
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