THERAPY: Assess the Penumbra System in the Treatment of Acute Stroke

• Sponsor: Penumbra Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01429350
• Collaborator: (none)
• Enrollment: 108
• Locations: 4
• Arms: 2
• Duration (Months): 53
• Patients Per Site: 27
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this trial is to assess the safety and effectiveness of the Penumbra System as an adjunctive treatment to intravenous (IV) recombinant human tissue plasminogen activator (rtPA)in patients with acute ischemic stroke from large vessel occlusion in the brain. IV rtPA is the only drug approved for the treatment of acute ischemic stroke but it does not work very well in cases where the stroke is caused by a large vessel occlusion. The hypothesis being tested is to determine if the addition of a treatment by a mechanical thrombectomy device like the Penumbra System can improve the clinical outcome of the patient over just using IV rtPA alone.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA); Device: Penumbra System	Phase 4

Detailed Description

Current therapies for acute stroke are limited to the intravenous administration of a intravenous (IV) recombinant human tissue plasminogen activator (rtPA) for thrombolysis of the affected cerebral arteries within 3-4.5 hours from symptom onset, and the use of intra-arterial (IA) endovascular mechanical clot retrieval devices within 8 hours from ictus, all of which have limitations as mono therapies. For example, IV rtPA may not be very efficacious in large vessel occlusion and the long term effects of mechanical thrombectomy devices on patient functional outcome is unknown. This is a randomized, concurrent controlled study to assess the safety and effectiveness of the Penumbra System as adjunctive therapy to IV rtPA in the acute intervention of acute ischemic stroke. Patients presenting with symptoms of acute ischemic stroke who have evidence of a large clot burden (clot length > 8mm) in the anterior circulation will be assigned to either IV rtPA therapy alone (0.9mg/kg to a maximum of 90mg) or a combined IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and intra-arterial (IA) adjunctive treatment with the Penumbra System. Each treated patient will be followed and assessed for 3 months after enrollment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The THERAPY Trial: The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IV rtPA IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg	Drug: intravenous (IV) recombinant human tissue plasminogen activator (rtPA); 0.9mg/kg to a maximum of 90mg; Other Names: recombinant tissue plasminogen activator, Alteplase
Experimental: IV rtPA and IA Penumbra System Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System	Device: Penumbra System; The Penumbra System is an aspiration based mechanical thrombectomy device

Outcome Measures

Primary Outcome Measures

1. Good Functional Outcome as Defined by a Modified Rankin Score of 0-2 [90 days]

   The assessor is blinded to patient treatment assignment.

2. Incidence of All Serious Adverse Events [90 days]

   A Serious Adverse Event is defined as an event that: Led to death Led to a serious deterioration in the health of the patient that: Resulted in life-threatening illness or injury Resulted in permanent impairment of a body structure or a body function Required in-patient hospitalization or prolongation of existing hospitalization Resulted in medical or surgical intervention to arrest permanent impairment to body structure or a body function Led to fetal distress, fetal death or a congenital abnormality or birth defect

Secondary Outcome Measures

1. Good Clinical Outcome [30 days]

   Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIH stroke scale score at Discharge, a NIH stroke scale score of 0-1 at Discharge; or a 30-day modified Rankin scale score of 0-2

2. Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage [90 days]

   A symptomatic intracranial hemorrhage is defined as 24 hour CT evidence of an ECASS defined ICH and a 4-point or more worsening of the NIH Stroke Scale score

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. From 18 to 85 years of age

2. Present with symptoms consistent with an acute ischemic stroke and eligible for IV rtPA therapy (patients presenting 3-4.5 hrs from symptom onset are not eligible if they are >80 yrs of age, have a history of stroke and diabetes, anticoagulant use (even if INR is <1.7) and have a NIHSS score >25

3. Evidence of a large vessel occlusion in the anterior circulation with a clot length of 8mm or longer

4. NIH Stroke Scale (NIHSS) score 8 or greater or aphasic at presentation

5. Signed informed consent

Exclusion Criteria:

1. History of stroke in the past 3 months.

2. Females who are pregnant

3. Pre-existing neurological or psychiatric disease that could confound the study results such as a pre-stroke mRS score 1 or greater

4. Known severe allergy to contrast media

5. Uncontrolled hypertension (defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg)

6. CT evidence of the following conditions at randomization:

• Significant mass effect with midline shift

• Any acute ischemic changes in >1/3 of the affected middle cerebral artery territory

• Evidence of intracranial hemorrhage

1. Angiographic evidence of tantem extracranial occlusion or an arterial stenosis proximal to the occlusion that requires treatment prior to thrombus removal. Moderate stenosis not requiring treatment is not an exclusion

2. Angiographic evidence of preexisting arterial injury

3. Rapidly improving neurological status prior to randomization

4. Bilateral stroke

5. Intracranial tumors

6. Known history of cerebral aneurysm or arteriovenous malfunction

7. Known hemorrhagic diathesis, coagulation deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7

8. Baseline platelets <50,000

9. Use of IV heparin in the past 48 hours with PPT >1.5 times the normalized ratio

10. Pre-treatment glucose <50mg/dL or >300mg/dL

11. Life expectancy less than 90 days prior to stroke onset

12. Participation in another clinical investigation that could confound the evaluation of the study device

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Endovascular Surgical Neuroradiology, Swedish Medical Center	Denver	Colorado	United States	80112
2	Department of Neurological Surgery	Gainesville	Florida	United States	32610
3	Neurosurgery, Rush University Medical Center	Chicago	Illinois	United States	60612
4	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Penumbra Inc.

Investigators

• Principal Investigator: J Mocco, MD, MS, Vanderbilt University Medical Center
• Principal Investigator: Pooja Khatri, MD, Department of Neurology, University of Cincinnati
• Principal Investigator: Osama Zaidat, MD, MSc, Neurointerventional Program, Medical College of Wisconsin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Penumbra Inc.
• ClinicalTrials.gov Identifier: NCT01429350
• Other Study ID Numbers: CLP 4338
• First Posted: Sep 7, 2011
• Last Update Posted: Sep 22, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Penumbra Inc.: ischemic stroke; acute intervention; thrombolysis; rtPA; internal carotid artery; middle cerebral artery; mechanical thrombectomy; Penumbra System; clot length; mRS; NIHSS
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Tissue Plasminogen Activator; Plasminogen

Study Results

Participant Flow

Arm/Group Title	IV rtPA	IV rtPA and IA Penumbra System
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg	Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device
Period Title: Overall Study
STARTED	53	55
As-Treated	62	43
Per Protocol	41	37
90 Day	46	50
COMPLETED	46	50
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	IV rtPA	IV rtPA and IA Penumbra System	Total
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg	Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device	Total of all reporting groups
Overall Participants	53	55	108
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70 (10)	67 (11)	68.7 (10.9)
Sex: Female, Male (Count of Participants)
Female	30 56.6%	21 38.2%	51 47.2%
Male	23 43.4%	34 61.8%	57 52.8%

Outcome Measures

1. Primary Outcome

Title	Good Functional Outcome as Defined by a Modified Rankin Score of 0-2
Description	The assessor is blinded to patient treatment assignment.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV rtPA	IV rtPA and IA Penumbra System
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg	Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device
Measure Participants	46	50
Count of Participants [Participants]	14 26.4%	19 34.5%

2. Primary Outcome

Title	Incidence of All Serious Adverse Events
Description	A Serious Adverse Event is defined as an event that: Led to death Led to a serious deterioration in the health of the patient that: Resulted in life-threatening illness or injury Resulted in permanent impairment of a body structure or a body function Required in-patient hospitalization or prolongation of existing hospitalization Resulted in medical or surgical intervention to arrest permanent impairment to body structure or a body function Led to fetal distress, fetal death or a congenital abnormality or birth defect
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

The number of participants here are taken from the as-treated population, where IV tPA alone is 62 which differs from the number of initial participants started based on participant flow. This is due to 9 subjects who were randomized to Penumbra System receiving IV tPA Alone and no Penumbra System was used.

Arm/Group Title	IV rtPA	IV rtPA and IA Penumbra System
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg	Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device
Measure Participants	62	43
Count of Participants [Participants]	30 56.6%	18 32.7%

3. Secondary Outcome

Title	Good Clinical Outcome
Description	Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIH stroke scale score at Discharge, a NIH stroke scale score of 0-1 at Discharge; or a 30-day modified Rankin scale score of 0-2
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

30 day good clinical outcome based on ITT (intent-to-treat) population.

Arm/Group Title	IV rtPA	IV rtPA and IA Penumbra System
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg	Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device
Measure Participants	53	53
Count of Participants [Participants]	17 32.1%	24 43.6%

4. Secondary Outcome

Title	Incidence of Symptomatic and Asymptomatic Intracranial Hemorrhage
Description	A symptomatic intracranial hemorrhage is defined as 24 hour CT evidence of an ECASS defined ICH and a 4-point or more worsening of the NIH Stroke Scale score
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

The number of participants here are taken from the as-treated population, where IV tPA alone is 62 which differs from the number of initial participants started based on participant flow. This is due to 9 subjects who were randomized to Penumbra System receiving IV tPA Alone and no Penumbra System was used.

Arm/Group Title	IV rtPA	IV rtPA and IA Penumbra System
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg	Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device
Measure Participants	62	43
Count of Participants [Participants]	6 11.3%	4 7.3%

Adverse Events

Adverse Event Reporting Description	The number of participants are taken from the as-treated population. Serious Adverse Events: The number of participants are taken from the as-treated population, where IV tPA alone is 62 which differs from the number of initial participants. This is due to 9 subjects who were randomized to Penumbra System receiving IV tPA Alone and no Penumbra System was used.
Arm/Group Title	IV rtPA		IV rtPA and IA Penumbra System
Arm/Group Description	IV infusion of rtPA at 0.9mg/kg to a maximum of 90mg intravenous (IV) recombinant human tissue plasminogen activator (rtPA): 0.9mg/kg to a maximum of 90mg		Dual IV rtPA therapy (0.9mg/kg to a maximum of 90mg) and IA adjunctive treatment with the Penumbra System Penumbra System: The Penumbra System is an aspiration based mechanical thrombectomy device
All Cause Mortality
	IV rtPA		IV rtPA and IA Penumbra System
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IV rtPA		IV rtPA and IA Penumbra System
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/62 (51.6%)		20/43 (46.5%)
Cardiac disorders
Acute myocardial infarction	2/62 (3.2%)		1/43 (2.3%)
Arrhythmia	1/62 (1.6%)		0/43 (0%)
Atrial fibrillation	2/62 (3.2%)		0/43 (0%)
Cardiac arrest	0/62 (0%)		1/43 (2.3%)
Cardiac failure congestive	0/62 (0%)		1/43 (2.3%)
Cardiogenic shock	0/62 (0%)		1/43 (2.3%)
Gastrointestinal disorders
Ventricular fibrillation	1/62 (1.6%)		1/43 (2.3%)
Dysphagia	7/62 (11.3%)		3/43 (7%)
Gastrointestinal haemorrhage	2/62 (3.2%)		1/43 (2.3%)
Haematochezia	0/62 (0%)		1/43 (2.3%)
Hematemesis	2/62 (3.2%)		1/43 (2.3%)
General disorders
Chest pain	1/62 (1.6%)		0/43 (0%)
Thrombosis in device	0/62 (0%)		1/43 (2.3%)
Vessel puncture site haematoma	0/62 (0%)		1/43 (2.3%)
Infections and infestations
Enterocolitis infectious	1/62 (1.6%)		0/43 (0%)
Pneumonia	0/62 (0%)		1/43 (2.3%)
Sepsis	1/62 (1.6%)		2/43 (4.7%)
Urinary tract infection	1/62 (1.6%)		0/43 (0%)
Injury, poisoning and procedural complications
Gun shot wound	1/62 (1.6%)		0/43 (0%)
Metabolism and nutrition disorders
Malnutrition	0/62 (0%)		1/43 (2.3%)
Nervous system disorders
Aphasia	0/62 (0%)		1/43 (2.3%)
Brain oedema	3/62 (4.8%)		1/43 (2.3%)
Carotid artery occlusion	0/62 (0%)		1/43 (2.3%)
Cerebral haemorrhage	1/62 (1.6%)		0/43 (0%)
Cerebrovascular accident	6/62 (9.7%)		1/43 (2.3%)
Haemorrhage intracranial	3/62 (4.8%)		2/43 (4.7%)
Haemorrhagic transformation stroke	1/62 (1.6%)		0/43 (0%)
Intraventricular haemorrhage	1/62 (1.6%)		0/43 (0%)
Ischaemic stroke	0/62 (0%)		1/43 (2.3%)
Partial seizures	1/62 (1.6%)		0/43 (0%)
Subarachnoid haemorrhage	0/62 (0%)		2/43 (4.7%)
Psychiatric disorders
Mental status changes	0/62 (0%)		1/43 (2.3%)
Renal and urinary disorders
Haematuria	0/62 (0%)		1/43 (2.3%)
Renal failure	1/62 (1.6%)		0/43 (0%)
Renal failure acute	2/62 (3.2%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/62 (0%)		1/43 (2.3%)
Pneumonia aspiration	0/62 (0%)		1/43 (2.3%)
Pulmonary embolism	1/62 (1.6%)		0/43 (0%)
Respiratory failure	3/62 (4.8%)		3/43 (7%)
Vascular disorders
Deep vein thrombosis	1/62 (1.6%)		0/43 (0%)
Haemorrhage	1/62 (1.6%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	IV rtPA		IV rtPA and IA Penumbra System
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/62 (93.5%)		42/43 (97.7%)
Blood and lymphatic system disorders
Anaemia	4/62 (6.5%)		8/43 (18.6%)
Anaemia macrocytic	0/62 (0%)		1/43 (2.3%)
Leukocytosis	5/62 (8.1%)		4/43 (9.3%)
Leukopenia	2/62 (3.2%)		0/43 (0%)
Thrombocytopenia	2/62 (3.2%)		2/43 (4.7%)
Thrombocytosis	1/62 (1.6%)		0/43 (0%)
Cardiac disorders
Acute Myocardial Infarction	4/62 (6.5%)		1/43 (2.3%)
Aortic valve sclerosis	0/62 (0%)		1/43 (2.3%)
Arrhythmia	1/62 (1.6%)		0/43 (0%)
Atrial Fibrillation	11/62 (17.7%)		10/43 (23.3%)
Atrial flutter	1/62 (1.6%)		1/43 (2.3%)
Atrial thrombosis	1/62 (1.6%)		0/43 (0%)
Atrioventricular block first degree	0/62 (0%)		1/43 (2.3%)
Bradycardia	4/62 (6.5%)		2/43 (4.7%)
Cardiac arrest	0/62 (0%)		1/43 (2.3%)
Cardiac failure congestive	0/62 (0%)		4/43 (9.3%)
Cardiogenic shock	0/62 (0%)		1/43 (2.3%)
Cardiomegaly	0/62 (0%)		1/43 (2.3%)
Diastolic dysfunction	0/62 (0%)		2/43 (4.7%)
Extrasystoles	1/62 (1.6%)		0/43 (0%)
Heart valve incompetence	0/62 (0%)		1/43 (2.3%)
Left valve incomptence	0/62 (0%)		1/43 (2.3%)
Left atrial dilatation	0/62 (0%)		1/43 (2.3%)
Mitral valve calcification	0/62 (0%)		1/43 (2.3%)
Palpitations	1/62 (1.6%)		0/43 (0%)
Sinus tachycardia	1/62 (1.6%)		0/43 (0%)
Supraventricular tachycardia	0/62 (0%)		2/43 (4.7%)
Tachycardia	1/62 (1.6%)		0/43 (0%)
Ventricular extrasystoles	0/62 (0%)		1/43 (2.3%)
Ventricular fibrillation	1/62 (1.6%)		1/43 (2.3%)
Ventricular hypokinesia	0/62 (0%)		1/43 (2.3%)
Ventricular tachycardia	0/62 (0%)		3/43 (7%)
Congenital, familial and genetic disorders
Atrial septal defect	1/62 (1.6%)		0/43 (0%)
Congenital cystic kidney disease	0/62 (0%)		1/43 (2.3%)
Ear and labyrinth disorders
Ear pain	0/62 (0%)		1/43 (2.3%)
Eye disorders
Conjunctivitis	0/62 (0%)		1/43 (2.3%)
Dry Eye	1/62 (1.6%)		0/43 (0%)
Eye pain	1/62 (1.6%)		0/43 (0%)
Gastrointestinal disorders
Abdominal distension	1/62 (1.6%)		0/43 (0%)
Abdominal pain	1/62 (1.6%)		0/43 (0%)
Constipation	9/62 (14.5%)		6/43 (14%)
Diarrhoea	4/62 (6.5%)		2/43 (4.7%)
Dysphagia	9/62 (14.5%)		5/43 (11.6%)
Gastritis	1/62 (1.6%)		1/43 (2.3%)
Gastrointestinal haemorrhage	3/62 (4.8%)		1/43 (2.3%)
Gastrooesophageal reflux disease	1/62 (1.6%)		0/43 (0%)
Gingival bleeding	1/62 (1.6%)		0/43 (0%)
Haematochezia	0/62 (0%)		1/43 (2.3%)
Hematesis	1/62 (1.6%)		0/43 (0%)
Mouth haemorrhage	1/62 (1.6%)		0/43 (0%)
Nausea	7/62 (11.3%)		1/43 (2.3%)
General disorders
Peptic ulcer	1/62 (1.6%)		0/43 (0%)
Vomiting	3/62 (4.8%)		1/43 (2.3%)
Asthenia	0/62 (0%)		1/43 (2.3%)
Chest pain	4/62 (6.5%)		0/43 (0%)
Facial pain	0/62 (0%)		1/43 (2.3%)
Fatigue	0/62 (0%)		1/43 (2.3%)
Impaired healing	1/62 (1.6%)		0/43 (0%)
Oedema	1/62 (1.6%)		0/43 (0%)
Oedema peripheral	1/62 (1.6%)		0/43 (0%)
Pain	1/62 (1.6%)		2/43 (4.7%)
Pyrexia	7/62 (11.3%)		5/43 (11.6%)
Thrombosis in device	0/62 (0%)		1/43 (2.3%)
Unevaluable event	0/62 (0%)		1/43 (2.3%)
Vessel puncture site haematoma	1/62 (1.6%)		1/43 (2.3%)
Vessel puncture site haemorrhage	1/62 (1.6%)		0/43 (0%)
Hypovolaemia	1/62 (1.6%)		0/43 (0%)
Immune system disorders
Hypersensitivity	1/62 (1.6%)		0/43 (0%)
Infections and infestations
Bronchitis	0/62 (0%)		1/43 (2.3%)
Bronchopneumonia	0/62 (0%)		1/43 (2.3%)
Candidiasis	0/62 (0%)		1/43 (2.3%)
Cellulitis	1/62 (1.6%)		1/43 (2.3%)
Clostridal infection	0/62 (0%)		1/43 (2.3%)
Clostridium difficile colitis	2/62 (3.2%)		0/43 (0%)
Enterocolitis infectious	1/62 (1.6%)		0/43 (0%)
Eosophageal candiasis	0/62 (0%)		1/43 (2.3%)
Oral candiasis	3/62 (4.8%)		1/43 (2.3%)
Oral infection	1/62 (1.6%)		0/43 (0%)
Parotitis	0/62 (0%)		1/43 (2.3%)
Pneumonia	2/62 (3.2%)		1/43 (2.3%)
Sepsis	1/62 (1.6%)		2/43 (4.7%)
Sinusitis	0/62 (0%)		1/43 (2.3%)
Upper respiratory tract infection	1/62 (1.6%)		1/43 (2.3%)
Urinary tract infection	16/62 (25.8%)		12/43 (27.9%)
Injury, poisoning and procedural complications
Contusion	0/62 (0%)		2/43 (4.7%)
Fall	2/62 (3.2%)		3/43 (7%)
Gun shot wound	1/62 (1.6%)		0/43 (0%)
Haematuria traumatic	1/62 (1.6%)		0/43 (0%)
Incision site complication	1/62 (1.6%)		0/43 (0%)
Incision site haemorrhage	0/62 (0%)		1/43 (2.3%)
Incision site hypoaesthesia	1/62 (1.6%)		0/43 (0%)
Joint dislocation	0/62 (0%)		1/43 (2.3%)
Laceration	1/62 (1.6%)		1/43 (2.3%)
Procedural nausea	1/62 (1.6%)		0/43 (0%)
Scrotal haematoma	0/62 (0%)		1/43 (2.3%)
Subdural haemorrhage	1/62 (1.6%)		0/43 (0%)
Tongue injury	0/62 (0%)		1/43 (2.3%)
Transfusion reaction	0/62 (0%)		1/43 (2.3%)
Wound	1/62 (1.6%)		0/43 (0%)
Investigations
Activated partial thromboplastin time prolonged	0/62 (0%)		1/43 (2.3%)
Antithrombin III decreased	1/62 (1.6%)		0/43 (0%)
Blood calcium decreased	0/62 (0%)		1/43 (2.3%)
Blood magnesium decreased	1/62 (1.6%)		0/43 (0%)
Body temperature increased	0/62 (0%)		1/43 (2.3%)
Electrocardiogram QT prolonged	1/62 (1.6%)		0/43 (0%)
Haemoglobin decreased	1/62 (1.6%)		0/43 (0%)
Hepatic enzyme increased	2/62 (3.2%)		1/43 (2.3%)
Troponin increased	0/62 (0%)		2/43 (4.7%)
White blood cell count increased	1/62 (1.6%)		0/43 (0%)
Metabolism and nutrition disorders
Dehydration	1/62 (1.6%)		1/43 (2.3%)
Diabetes mellitus	0/62 (0%)		1/43 (2.3%)
Dyslipidaemia	0/62 (0%)		1/43 (2.3%)
Electrolyte imbalance	2/62 (3.2%)		0/43 (0%)
Gout	1/62 (1.6%)		0/43 (0%)
Hyperchloraemia	1/62 (1.6%)		0/43 (0%)
Hypercholesterolaemia	2/62 (3.2%)		1/43 (2.3%)
Hyperglycaemia	4/62 (6.5%)		4/43 (9.3%)
Hyperkalaemia	2/62 (3.2%)		0/43 (0%)
Hyperlipidaemia	2/62 (3.2%)		4/43 (9.3%)
Hypernatraemia	2/62 (3.2%)		3/43 (7%)
Hypertriglyceridaemia	0/62 (0%)		1/43 (2.3%)
Hypervolaemia	1/62 (1.6%)		0/43 (0%)
Hypocalcaemia	2/62 (3.2%)		1/43 (2.3%)
Hypochloraemia	0/62 (0%)		1/43 (2.3%)
Hypoglycaemia	2/62 (3.2%)		0/43 (0%)
Hypokalaemia	12/62 (19.4%)		11/43 (25.6%)
Hypomagnesaemia	3/62 (4.8%)		5/43 (11.6%)
Hyponatraemia	3/62 (4.8%)		0/43 (0%)
Hypophosphataemia	2/62 (3.2%)		1/43 (2.3%)
Malnutrition	1/62 (1.6%)		5/43 (11.6%)
Metabolic acidosis	1/62 (1.6%)		1/43 (2.3%)
Vitamin B12 deficiency	0/62 (0%)		1/43 (2.3%)
Vitamin D deficiency	1/62 (1.6%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/62 (0%)		2/43 (4.7%)
Back pain	0/62 (0%)		1/43 (2.3%)
Muscle spasms	1/62 (1.6%)		0/43 (0%)
Muscular weakness	0/62 (0%)		1/43 (2.3%)
Musculoskeletal stiffness	0/62 (0%)		1/43 (2.3%)
Myalgia	1/62 (1.6%)		0/43 (0%)
Neck pain	1/62 (1.6%)		2/43 (4.7%)
Pain in extremity	3/62 (4.8%)		3/43 (7%)
Nervous system disorders
Aphasia	0/62 (0%)		1/43 (2.3%)
Basal ganglia haemorrhage	0/62 (0%)		1/43 (2.3%)
Brain oedema	9/62 (14.5%)		5/43 (11.6%)
Carotid artery dissection	0/62 (0%)		1/43 (2.3%)
Carotid artery occlusion	0/62 (0%)		1/43 (2.3%)
Cerebellar infarction	0/62 (0%)		1/43 (2.3%)
Cerebral artery embolism	0/62 (0%)		1/43 (2.3%)
Cerebral artery occlusion	1/62 (1.6%)		0/43 (0%)
Cerebral artery stenosis	0/62 (0%)		1/43 (2.3%)
Cerebral haemorrhage	1/62 (1.6%)		0/43 (0%)
Cerebral infarction	1/62 (1.6%)		0/43 (0%)
Cerebral thrombosis	0/62 (0%)		1/43 (2.3%)
Cerebrovascular accident	7/62 (11.3%)		1/43 (2.3%)
Cerebrovascular spasm	0/62 (0%)		4/43 (9.3%)
Complex regional pain syndrome	1/62 (1.6%)		0/43 (0%)
Convulsion	2/62 (3.2%)		2/43 (4.7%)
Dementia Alzheimer's type	1/62 (1.6%)		0/43 (0%)
Dizziness	2/62 (3.2%)		0/43 (0%)
Haemorrhage intracranial	19/62 (30.6%)		14/43 (32.6%)
Haemorrhagic cerebral infarction	1/62 (1.6%)		1/43 (2.3%)
Haemorrhagic transformation stroke	2/62 (3.2%)		1/43 (2.3%)
Headache	8/62 (12.9%)		6/43 (14%)
Hydrocephalus	8/62 (12.9%)		6/43 (14%)
Hypertonia	0/62 (0%)		1/43 (2.3%)
Hypoaesthesia	2/62 (3.2%)		1/43 (2.3%)
Intracranial pressure increased	2/62 (3.2%)		0/43 (0%)
Intraventricular haemorrhage	1/62 (1.6%)		0/43 (0%)
Ischaemic stroke	0/62 (0%)		1/43 (2.3%)
Lethargy	1/62 (1.6%)		1/43 (2.3%)
Loss of consciousness	1/62 (1.6%)		0/43 (0%)
Memory impairment	1/62 (1.6%)		0/43 (0%)
Neurological decompensation	0/62 (0%)		1/43 (2.3%)
Neuropathy peripheral	1/62 (1.6%)		0/43 (0%)
Partial seizures	1/62 (1.6%)		1/43 (2.3%)
Somnolence	2/62 (3.2%)		1/43 (2.3%)
Stroke in evolution	1/62 (1.6%)		1/43 (2.3%)
Subarachnoid haemorrhage	0/62 (0%)		3/43 (7%)
Syncope	0/62 (0%)		1/43 (2.3%)
Psychiatric disorders
Agitation	0/62 (0%)		3/43 (7%)
Anxiety	1/62 (1.6%)		1/43 (2.3%)
Anxiety disorder	1/62 (1.6%)		0/43 (0%)
Confusional state	0/62 (0%)		1/43 (2.3%)
Delirium	0/62 (0%)		1/43 (2.3%)
Depression	7/62 (11.3%)		5/43 (11.6%)
Hallucination	0/62 (0%)		1/43 (2.3%)
Insomnia	5/62 (8.1%)		0/43 (0%)
Mental status changes	2/62 (3.2%)		3/43 (7%)
Restlessness	0/62 (0%)		1/43 (2.3%)
Sleep disorder	0/62 (0%)		1/43 (2.3%)
Calculus urinary	0/62 (0%)		1/43 (2.3%)
Renal and urinary disorders
Cystitis noninfective	0/62 (0%)		1/43 (2.3%)
Haematuria	0/62 (0%)		3/43 (7%)
Incontinence	1/62 (1.6%)		1/43 (2.3%)
Renal failure	2/62 (3.2%)		0/43 (0%)
Renal failure acute	3/62 (4.8%)		2/43 (4.7%)
Renal impairment	0/62 (0%)		1/43 (2.3%)
Reproductive system and breast disorders
Urinary retention	0/62 (0%)		3/43 (7%)
Benign prostatic hyperplasia	1/62 (1.6%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/62 (0%)		1/43 (2.3%)
Acute respiratory failure	1/62 (1.6%)		1/43 (2.3%)
Atelectasis	0/62 (0%)		1/43 (2.3%)
Chronic obstructive pulmonary disease	0/62 (0%)		1/43 (2.3%)
Cough	1/62 (1.6%)		0/43 (0%)
Diaphragmatic hernia	0/62 (0%)		1/43 (2.3%)
Dyspnoea	1/62 (1.6%)		0/43 (0%)
Epistaxis	1/62 (1.6%)		0/43 (0%)
Hyperventilation	1/62 (1.6%)		0/43 (0%)
Hypoxia	1/62 (1.6%)		0/43 (0%)
Lung infiltration	0/62 (0%)		1/43 (2.3%)
Nasal congestion	1/62 (1.6%)		0/43 (0%)
Pleural effusion	1/62 (1.6%)		0/43 (0%)
Pneumonia aspiration	4/62 (6.5%)		5/43 (11.6%)
Pulmonary congestion	1/62 (1.6%)		2/43 (4.7%)
Pulmonary embolism	3/62 (4.8%)		0/43 (0%)
Pulmonary oedema	1/62 (1.6%)		0/43 (0%)
Respiratory failure	3/62 (4.8%)		3/43 (7%)
Wheezing	1/62 (1.6%)		1/43 (2.3%)
Skin and subcutaneous tissue disorders
Blister	0/62 (0%)		1/43 (2.3%)
Ecchymosis	1/62 (1.6%)		0/43 (0%)
Rash	1/62 (1.6%)		1/43 (2.3%)
Skin lesion	1/62 (1.6%)		0/43 (0%)
Skin ulcer	0/62 (0%)		1/43 (2.3%)
Vascular disorders
Accelerated hypertension	2/62 (3.2%)		0/43 (0%)
Deep vein thrombosis	3/62 (4.8%)		0/43 (0%)
Haematoma	1/62 (1.6%)		0/43 (0%)
Haemorrhage	1/62 (1.6%)		0/43 (0%)
Hypertension	4/62 (6.5%)		6/43 (14%)
Hypotension	5/62 (8.1%)		9/43 (20.9%)
Orthostatic hypotension	2/62 (3.2%)		1/43 (2.3%)
Peripheral arterial occlusive disease	0/62 (0%)		1/43 (2.3%)
Thrombophlebitis	1/62 (1.6%)		0/43 (0%)
Thrombophlebitis superficial	1/62 (1.6%)		0/43 (0%)
Thrombosis	0/62 (0%)		1/43 (2.3%)
Vascular calcification	0/62 (0%)		1/43 (2.3%)
Vasospasm	0/62 (0%)		7/43 (16.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.