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Slow enrollment
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| Name | Class |
|---|---|
| Yale University | OTHER |
| Thomas Jefferson University | OTHER |
| University of Illinois at Chicago | OTHER |
| Wake Forest University Health Sciences |
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The primary objective of the study is to determine the optimal intra-arterial drug treatment regimen for arterial lumen restoration post cerebral vasospasm following aneurysmal subarachnoid hemorrhage. The secondary objective is to evaluate clinical outcome at 90 days post discharge following optimal intra-arterial drug treatment for cerebral vasospasm.
We hypothesize that Intra-arterial (IA) infusion of a combination of multiple vasodilators is more efficacious than single agent treatment cerebral vasospasm therapy.
All procedures done as a part of this study are standard hospital care procedures done to treat cerebral vasospasm and all drugs to be used are FDA approved.
The primary objective of the study is to determine the optimal intra-arterial drug treatment regimen for arterial lumen restoration post cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
The secondary objective is to evaluate clinical outcome at 90 days post discharge following optimal intra-arterial drug treatment for cerebral vasospasm.
This study is a prospective multicenter randomized trial. The primary outcome measure is the Post infusion improvement ratio (PIIR) assessed 10 minutes after completion of the intra-arterial infusion. PIIR is a measure of arterial lumen diameter pre and post intra-arterial drug infusion in the presenting vasospasmic blood vessel.
Modified Rankin score (mRS) at 3 months post hospital discharge will be recorded as a secondary outcome to assess clinical outcome.
The interventions in this study are a part of routine standard of care (SOC) procedures for cerebral vasospasm treatment. Following surgical or endovascular intervention for aneurysmal Subarachnoid Hemorrhage (aSAH) if patients develop cerebral vasospasm refractory to maximal medical management, endovascular treatment by intra-arterial drug infusion of single drug agent or cocktail drug agents will be initiated.
Study participants will be randomly assigned to one of the three treatment groups where one single drug agent or cocktail drug agents will be intra-arterially administered. Pre & post infusion vasospasmic vessel diameters will be compared. The change in diameter will be quantified based on the mean percentage change. Three months post hospital discharge, study participants will be followed up in clinic to evaluate clinical outcome.
The study will require 330 patients in total. The patient population will be hospitalized patients presenting with cerebral vasospasm post aneurysmal subarachnoid hemorrhage.
Subjects will be stratified by randomization into 3 treatment groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nicardipine | Active Comparator | Group 1 : Nicardipine 5mg per circulation intra-arterial injection, Pharmacological angioplasty |
|
| Verapamil | Active Comparator | Group 3: Verapamil 10mg per circulation intra-arterial injection, Pharmacological angioplasty |
|
| Nicardipine + Verapamil + Nitroglycerin | Active Comparator | Group 4 : Nicardipine 5mg + Verapamil 10mg + Nitroglycerin 200mcg in 4cc 5 % dextrose in water , intra-arterial injection, Pharmacological angioplasty |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicardipine | Drug | Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
|
| Measure | Description | Time Frame |
|---|---|---|
| Post Infusion Improvement Ratio (PIIR) | Post infusion improvement ratio (PIIR) = ((B - A) / A) *100 A = pre-infusion blood vessel diameter B = post infusion blood vessel diameter | pre pharmacological angioplasty blood vessel diameter - 0 min, post pharmacological angioplasty blood vessel diameter- 10 min after infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Disability or Dependence in Daily Activities as Assessed by the Modified Rankin Score | The modified Rankin Scale (mRS) is used to assess the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The Modified Rankin Score (mRS) is scored as follows: 0 - No symptoms.
|
| Measure | Description | Time Frame |
|---|---|---|
| Intra-cranial Pressure | Intra-cranial pressure will be measured 1 day prior to vasospasm treatment and 1 day after vasospasm treatment | 1 day prior to procedure & 1 day after the procedure |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peng R Chen, MD | University of Texas Medical School at Houston | Principal Investigator |
| Ketan R Bulsara, MD, MBA | UConn Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale School of Medicine | New Haven | Connecticut | 06520 | United States | ||
| Northwell Health |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18638721 | Background | Dorsch NW, King MT. A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part I: Incidence and effects. J Clin Neurosci. 1994 Jan;1(1):19-26. doi: 10.1016/0967-5868(94)90005-1. | |
| 12744357 | Background | Treggiari MM, Walder B, Suter PM, Romand JA. Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage. J Neurosurg. 2003 May;98(5):978-84. doi: 10.3171/jns.2003.98.5.0978. |
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Of 92 enrolled participants, 91 met inclusion criteria and were randomized to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nicardipine | Group 1 : Nicardipine 5mg per circulation intra-arterial injection, Pharmacological angioplasty Nicardipine: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| FG001 | Verapamil | Group 3: Verapamil 10mg per circulation intra-arterial injection, Pharmacological angioplasty Verapamil: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| FG002 | Nicardipine + Verapamil + Nitroglycerin | Group 4 : Nicardipine 5mg + Verapamil 10mg + Nitroglycerin 200mcg in 4cc 5 % dextrose in water , intra-arterial injection, Pharmacological angioplasty Nicardipine + Verapamil + Nitroglycerin: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Includes all participants who received intervention.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Nicardipine | Group 1 : Nicardipine 5mg per circulation intra-arterial injection, Pharmacological angioplasty Nicardipine: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| BG001 | Verapamil |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Post Infusion Improvement Ratio (PIIR) | Post infusion improvement ratio (PIIR) = ((B - A) / A) *100 A = pre-infusion blood vessel diameter B = post infusion blood vessel diameter | Posted | Count of Participants | Participants | pre pharmacological angioplasty blood vessel diameter - 0 min, post pharmacological angioplasty blood vessel diameter- 10 min after infusion |
|
Up to 3 months
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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 | Nicardipine | Group 1 : Nicardipine 5mg per circulation intra-arterial injection, Pharmacological angioplasty Nicardipine: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Poor prognosis leading to death | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peng Roc Chen, MD | The University of Texas Health Science Center at Houston | 713-486-8016 | Peng.R.Chen@uth.tmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 9, 2021 | Apr 28, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020301 | Vasospasm, Intracranial |
| D013345 | Subarachnoid Hemorrhage |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D009529 | Nicardipine |
| D014700 | Verapamil |
| D005996 | Nitroglycerin |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
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| OTHER |
| Temple University | OTHER |
| Geisinger Clinic | OTHER |
| Northwell Health | OTHER |
| University of Michigan | OTHER |
| Lenox Hill Hospital | OTHER |
| Weatherhead Foundation | UNKNOWN |
| University of California, Irvine | OTHER |
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| Verapamil | Drug | Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
|
| Nicardipine + Verapamil + Nitroglycerin | Drug | Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
|
| 3 months post discharge from hospital |
| Manhasset |
| New York |
| 11030 |
| United States |
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
| Geisinger Clinic | Danville | Pennsylvania | 17822 | United States |
| University of Texas Medical School at Houston | Houston | Texas | 77030 | United States |
| 3176090 | Background | Biller J, Godersky JC, Adams HP Jr. Management of aneurysmal subarachnoid hemorrhage. Stroke. 1988 Oct;19(10):1300-5. doi: 10.1161/01.str.19.10.1300. No abstract available. |
| 3895589 | Background | Kassell NF, Sasaki T, Colohan AR, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke. 1985 Jul-Aug;16(4):562-72. doi: 10.1161/01.str.16.4.562. |
| 18312091 | Background | Keuskamp J, Murali R, Chao KH. High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2008 Mar;108(3):458-63. doi: 10.3171/JNS/2008/108/3/0458. |
| 19057319 | Background | Linfante I, Delgado-Mederos R, Andreone V, Gounis M, Hendricks L, Wakhloo AK. Angiographic and hemodynamic effect of high concentration of intra-arterial nicardipine in cerebral vasospasm. Neurosurgery. 2008 Dec;63(6):1080-6; discussion 1086-7. doi: 10.1227/01.NEU.0000327698.66596.35. |
| 15140728 | Background | Badjatia N, Topcuoglu MA, Pryor JC, Rabinov JD, Ogilvy CS, Carter BS, Rordorf GA. Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. AJNR Am J Neuroradiol. 2004 May;25(5):819-26. |
| 20098322 | Background | Pierot L, Aggour M, Moret J. Vasospasm after aneurysmal subarachnoid hemorrhage: recent advances in endovascular management. Curr Opin Crit Care. 2010 Apr;16(2):110-6. doi: 10.1097/MCC.0b013e3283372ef2. |
| 18239182 | Background | Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008 Mar;39(3):893-8. doi: 10.1161/STROKEAHA.107.492447. Epub 2008 Jan 31. |
Group 3: Verapamil 10mg per circulation intra-arterial injection, Pharmacological angioplasty Verapamil: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| BG002 | Nicardipine + Verapamil + Nitroglycerin | Group 4 : Nicardipine 5mg + Verapamil 10mg + Nitroglycerin 200mcg in 4cc 5 % dextrose in water , intra-arterial injection, Pharmacological angioplasty Nicardipine + Verapamil + Nitroglycerin: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | pounds (lbs) |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Number of Participants with history of hypertension | Count of Participants | Participants |
|
| Number of Participants with history of diabetes mellitus 1 or 2 | Count of Participants | Participants |
|
| Number of participants with morbid obesity | Count of Participants | Participants |
|
| Smoking History | Count of Participants | Participants |
|
| Alcohol History | Count of Participants | Participants |
|
| Substance Abuse History | Count of Participants | Participants |
|
| Number of Participants with History of Hypercholesterolemia | Count of Participants | Participants |
|
| OG002 | Nicardipine + Verapamil + Nitroglycerin | Group 4 : Nicardipine 5mg + Verapamil 10mg + Nitroglycerin 200mcg in 4cc 5 % dextrose in water , intra-arterial injection, Pharmacological angioplasty Nicardipine + Verapamil + Nitroglycerin: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm |
|
|
| Secondary | Disability or Dependence in Daily Activities as Assessed by the Modified Rankin Score | The modified Rankin Scale (mRS) is used to assess the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The Modified Rankin Score (mRS) is scored as follows: 0 - No symptoms.
| Data were not collected from 2 participants from the Nicardipine arm and 5 participants in the Nicardipine + Verapamil + Nitroglycerin arm because the assessment was not administered to them. | Posted | Mean | Standard Deviation | score on a scale | 3 months post discharge from hospital |
|
|
|
| Other Pre-specified | Intra-cranial Pressure | Intra-cranial pressure will be measured 1 day prior to vasospasm treatment and 1 day after vasospasm treatment | Not Posted | 1 day prior to procedure & 1 day after the procedure | Participants |
| 2 |
| 32 |
| 4 |
| 32 |
| 21 |
| 32 |
| EG001 | Verapamil | Group 3: Verapamil 10mg per circulation intra-arterial injection, Pharmacological angioplasty Verapamil: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm | 0 | 31 | 0 | 31 | 13 | 31 |
| EG002 | Nicardipine + Verapamil + Nitroglycerin | Group 4 : Nicardipine 5mg + Verapamil 10mg + Nitroglycerin 200mcg in 4cc 5 % dextrose in water , intra-arterial injection, Pharmacological angioplasty Nicardipine + Verapamil + Nitroglycerin: Pharmacological angioplasty: intra-arterial drug infusion via catheter to treat cerebral vasospasm | 3 | 29 | 5 | 29 | 27 | 29 |
| Subarachnoid hemorrhage leading to death | Nervous system disorders | Non-systematic Assessment |
|
| respiratory failure secondary to Subarachnoid hemorrhage leading to death | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Elevated Intracranial Pressure | Nervous system disorders | Non-systematic Assessment |
|
| Intracranial Hemorrhage | Nervous system disorders | Non-systematic Assessment |
|
| Stroke | Nervous system disorders | Non-systematic Assessment |
|
| recurrent subarachnoid hemorrhage | Nervous system disorders | Non-systematic Assessment |
|
| Acute Posthemorrhagic Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| COVID-19 | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Cerebral Spinal Fluid Leak | Nervous system disorders | Non-systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | Non-systematic Assessment |
|
| Dry Gangrene | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Elevated Intracranial Pressure | Nervous system disorders | Non-systematic Assessment |
|
| Fever | Immune system disorders | Non-systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | Non-systematic Assessment |
|
| Hyponatremia | Renal and urinary disorders | Non-systematic Assessment |
|
| Intracranial Hemorrhage | Nervous system disorders | Non-systematic Assessment |
|
| Aysymptomatic NSTEMI | Cardiac disorders | Non-systematic Assessment |
|
| Periorbital Edema | Infections and infestations | Non-systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Positive Culture | Gastrointestinal disorders | Non-systematic Assessment |
|
| Pseudoaneurysm | Vascular disorders | Non-systematic Assessment |
|
| Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Stroke | Nervous system disorders | Non-systematic Assessment |
|
| Subconjunctival Hemorrhage | Nervous system disorders | Non-systematic Assessment |
|
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D020300 | Intracranial Hemorrhages |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010627 |
| Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009574 | Nitro Compounds |