TREVO2: Randomized Trial Evaluating Performance of the Trevo Retriever Versus the Merci Retriever in Acute Ischemic Stroke

• Sponsor: Stryker Neurovascular (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01270867
• Collaborator: (none)
• Enrollment: 178
• Location: 1
• Arms: 2
• Duration (Months): 12.9
• Patients Per Site Per Month: 13.8

Study Details

Study Description

Brief Summary

To determine if the Trevo Retriever is as good or better than the Merci Retriever in restoring blood flow to the brain of a patient experiencing an acute ischemic stroke in a large vessel.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Device: Mechanical Thrombectomy	N/A

Detailed Description

The TREVO 2 protocol was designed to assess the safety and effectiveness of the Trevo Retriever device and determine if it is substantially equivalent to the predicate Merci Retriever. The trial utilized a Primary Effectiveness Endpoint of revascularization and a composite Primary Safety Endpoint that included procedure-related serious adverse events occurring within 24 hours of the procedure. Subjects who presented to enrolling centers with large ischemic strokes were screened for eligibility in the study. If a subject met eligibility criteria, then Informed Consent was obtained prior to commencing the angiogram. If all inclusion/exclusion criteria were confirmed, including the angiographic criteria, then the subject was randomized.The Primary Effectiveness Endpoint was successful revascularization of the target occlusion, using the TICI score. Success was determined by the central Core Lab.The Primary Safety Endpoint is a composite endpoint, described in the protocol as the "Incidence of procedure-related serious adverse events (PRSAEs) through 24 hours post procedure (-6/+12 hours) defined as: vascular perforation or intramural arterial dissection, symptomatic ICH, embolization to a previously uninvolved territory, access site complication requiring surgical repair or blood transfusion, intra-procedural mortality, device failure (in vivo breakage), or any other complications judged by the Clinical Events Committee (CEC) to be related to the procedure."

Study Design

• Study Type: Interventional
• Actual Enrollment: 178 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Thrombectomy REvascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO 2)
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Merci Retriever Merci Retriever is the predicate product that received FDA clearance in 2004. Merci Retriever a first generation mechanical thrombectomy device intended to remove clot and restore blood flow in a neurovascular vessel in the setting of acute ischemic stroke.	Device: Mechanical Thrombectomy; Each arm will use either Merci or Trevo as the primary Mechanical Thrombectomy device.
Experimental: Trevo Stentriever Trevo Retriever is a second generation mechanical thrombectomy device intended to remove clot and restore blood flow in a neurovascular vessel in the setting of acute ischemic stroke. The Trevo Retriever is a type of stent, specifically design to allow for clot integration into the device. The clot in the retriever is then removed and blood flow is restored.	Device: Mechanical Thrombectomy; Each arm will use either Merci or Trevo as the primary Mechanical Thrombectomy device.

Outcome Measures

Primary Outcome Measures

1. Primary Efficacy Endpoint [acute/procedural]

   Revascularization of the occluded territory, defined as at least TICI 2 flow in the treated territory after use of the assigned device. Thrombolysis in Cerebral Infarction (TICI) grading system for perfusion (ie blood flow through a vessel) Grade 0:No Perfusion. No antegrade flow beyond the point of occlusion. Grade 1:Penetration With Minimal Perfusion. Grade 2:Partial Perfusion. Grade 2a:Only partial filling (<2/3) of the entire vascular territory is visualized. Grade 2b:Complete filling of all of the expected vascular territory is visualized, but slower ... Grade 3:Complete Perfusion. For complete info see Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B et al. (2003) Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke 34: e109-e137.10.1161/01.STR.0000082721.62796.09 PubMed: 12869717[PubMed]

2. Primary Safety Endpoint [within 24 hours of procedure]

   Incidence of procedure-related serious adverse events (PRSAEs) through 24 hours post procedure (-6/+12 hours).

Secondary Outcome Measures

1. Secondary Endpoint [90 days]

   Good clinical outcomes at 90 days, as assessed by mRS (a "good" clinical outcome is defined as mRS </= 2) mRS 0-2 indicates functional independence 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead. https://en.wikipedia.org/wiki/Modified_Rankin_Sca

2. Secondary Endpoint [procedure through 90 days]

   All cause mortality at 90 days

3. Secondary Endpoint [24 hours]

   Incidence of asymptomatic intracranial hemorrhages (ICH) within 24 (-6/+12) hours post procedure

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Patient presenting with clinical signs and symptoms consistent with a diagnosis of

Acute Ischemic Stroke, and:

• Patient has failed IV t-PA therapy Or

• Patient is contraindicated for IV t-PA administration

• NIHSS 8 < NIHSS < 29

• Anticipated life expectancy of at least 6 months

• No significant pre-stroke disability (mRS < 1)

• Written informed consent to participate given by patient or legal representative

• Angiographic confirmation of a persistent large vessel occlusion in the internal carotid, middle cerebral (M1 and/or M2 segments), basilar and/or vertebral arteries

• Treatable within 8 hours of symptom onset, defined as the first pass being made with the assigned study device

Key Exclusion Criteria:

• Abnormal blood pressure and/or blood coagulation lab values

• Pregnancy

• Patient participating in another investigational drug or device study

• More than 1/3 of MCA or equivalent in non-MCA territory

• Baseline evidence of significant mass effect with midline shift, or hemorrhage, or intracranial tumor

• Bilateral stroke

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health Sciences University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Stryker Neurovascular

Investigators

• Principal Investigator: Raul G Nogueira, MD, Emory University
• Principal Investigator: Helmi Lutsep, MD, Oregon Health and Science University
• Principal Investigator: Wade Smith, MD, PhD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• American Stroke Association

Publications

None provided.

• Responsible Party: Stryker Neurovascular
• ClinicalTrials.gov Identifier: NCT01270867
• Other Study ID Numbers: DQR0038
• First Posted: Jan 5, 2011
• Last Update Posted: Aug 3, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Stryker Neurovascular: Ischemia; Stroke; Ischemic Stroke; Mechanical Thrombectomy; Brain; Brain clot; Cerebrovascular disease; Recanalization; Revascularization
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia

Study Results

Participant Flow

Arm/Group Title	Merci Retriever	Trevo Stentriever
Arm/Group Description	Patients who were randomized to the Merci Retriever	Patients who were randomized to the Trevo Stentriever
Period Title: Overall Study
STARTED	90	88
COMPLETED	89	88
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Merci Retriever	Trevo Stentriever	Total
Arm/Group Description	Patients who were randomized to the Merci Retriever	Patients who were randomized to the Trevo Stentriever	Total of all reporting groups
Overall Participants	90	88	178
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.0 (14.7)	67.4 (13.9)	67.2 (14.2)
Sex: Female, Male (Count of Participants)
Female	54 60%	48 54.5%	102 57.3%
Male	36 40%	40 45.5%	76 42.7%
Region of Enrollment (participants) [Number]
United States	89 98.9%	88 100%	177 99.4%
Spain	1 1.1%	0 0%	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Primary Efficacy Endpoint
Description	Revascularization of the occluded territory, defined as at least TICI 2 flow in the treated territory after use of the assigned device. Thrombolysis in Cerebral Infarction (TICI) grading system for perfusion (ie blood flow through a vessel) Grade 0:No Perfusion. No antegrade flow beyond the point of occlusion. Grade 1:Penetration With Minimal Perfusion. Grade 2:Partial Perfusion. Grade 2a:Only partial filling (<2/3) of the entire vascular territory is visualized. Grade 2b:Complete filling of all of the expected vascular territory is visualized, but slower ... Grade 3:Complete Perfusion. For complete info see Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B et al. (2003) Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke 34: e109-e137.10.1161/01.STR.0000082721.62796.09 PubMed: 12869717[PubMed]
Time Frame	acute/procedural

Outcome Measure Data

Analysis Population Description

Intent to treat analysis was performed. The non-inferiority hypothesis was tested with Blackwelder's method, assuming a one-sided alpha=0.025 and a clinically relevant non-inferiority margin of 10%.

Arm/Group Title	Merci Retriever	Trevo Stentriever
Arm/Group Description	Patients who were randomized to receive the Merci Retriever.	Patients who were randomized to receive the Trevo Stentriever.
Measure Participants	90	88
Number [participants]	54 60%	76 86.4%

2. Primary Outcome

Title	Primary Safety Endpoint
Description	Incidence of procedure-related serious adverse events (PRSAEs) through 24 hours post procedure (-6/+12 hours).
Time Frame	within 24 hours of procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Merci Retriever	Trevo Stentriever
Arm/Group Description	Patients who were randomized to receive the Merci Retriever.	Patients who were randomized to receive the Trevo Stentriever.
Measure Participants	90	88
Number [participants]	21 23.3%	13 14.8%

3. Secondary Outcome

Title	Secondary Endpoint
Description	Good clinical outcomes at 90 days, as assessed by mRS (a "good" clinical outcome is defined as mRS </= 2) mRS 0-2 indicates functional independence 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead. https://en.wikipedia.org/wiki/Modified_Rankin_Sca
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Merci Retriever	Trevo Stentriever
Arm/Group Description	Patients who were randomized to receive the Merci Retriever.	Patients who were randomized to receive the Trevo Stentriever.
Measure Participants	87	85
Number [participants]	19 21.1%	34 38.6%

4. Secondary Outcome

Title	Secondary Endpoint
Description	All cause mortality at 90 days
Time Frame	procedure through 90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Merci Retriever	Trevo Stentriever
Arm/Group Description	Patients who were randomized to receive the Merci Retriever.	Patients who were randomized to receive the Trevo Stentriever.
Measure Participants	89	88
Number [participants]	21 23.3%	29 33%

5. Secondary Outcome

Title	Secondary Endpoint
Description	Incidence of asymptomatic intracranial hemorrhages (ICH) within 24 (-6/+12) hours post procedure
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Merci Retriever	Trevo Stentriever
Arm/Group Description	Patients who were randomized to receive the Merci Retriever.	Patients who were randomized to receive the Trevo Stentriever.
Measure Participants	90	88
Number [participants]	48 53.3%	36 40.9%

Adverse Events

Time Frame	Each subject was followed for 90 days; The study period was 1 year.
Adverse Event Reporting Description	A study specific AE classification system was used to categorize Site Reported AEs and SAEs. The study used an independent clinical events committee, CT and MRI imaging core laboratory, a separate angiography core laboratory, and an independent data safety and monitoring board (DSMB) to ensure appropriate oversight and analysis.
Arm/Group Title	Merci Retriever		Trevo Stentriever
Arm/Group Description	Patients who were randomized to receive the Merci Retriever.		Patients who were randomized to receive the Trevo Stentriever.
All Cause Mortality
	Merci Retriever		Trevo Stentriever
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Merci Retriever		Trevo Stentriever
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/90 (43.3%)		41/88 (46.6%)
Cardiac disorders
Arrhythmia - Tachycardia	0/90 (0%)	0	1/88 (1.1%)	1
Atrial Fibrillation	1/90 (1.1%)	1	0/88 (0%)	0
Cardiac Arrest	0/90 (0%)	0	1/88 (1.1%)	1
Cardiopulmonary Arrest	0/90 (0%)	0	1/88 (1.1%)	1
Chest Pain	0/90 (0%)	0	2/88 (2.3%)	2
Congestive Heart Failure	1/90 (1.1%)	1	1/88 (1.1%)	1
Hypotension - Sustained - Tx	1/90 (1.1%)	1	2/88 (2.3%)	2
Stress Cardiomyopathy	1/90 (1.1%)	1	0/88 (0%)	0
Gastrointestinal disorders
GI Bleed	2/90 (2.2%)	2	0/88 (0%)	0
Other	1/90 (1.1%)	1	0/88 (0%)	0
Occult Blood	1/90 (1.1%)	1	1/88 (1.1%)	1
General disorders
Drug Reaction	1/90 (1.1%)	1	1/88 (1.1%)	1
Fever	1/90 (1.1%)	1	0/88 (0%)	0
Positive Cultures	0/90 (0%)	0	1/88 (1.1%)	1
Events With an Outcome of Death	2/90 (2.2%)	2	1/88 (1.1%)	1
Infections and infestations
Sepsis	1/90 (1.1%)	1	1/88 (1.1%)	1
Metabolism and nutrition disorders
Electrolyte Imbalance	0/90 (0%)	0	1/88 (1.1%)	1
Other	0/90 (0%)	0	1/88 (1.1%)	1
Musculoskeletal and connective tissue disorders
Joint/Extremity Pain	0/90 (0%)	0	1/88 (1.1%)	1
Nervous system disorders
Acute Mental Status Change/Confusion	1/90 (1.1%)	1	0/88 (0%)	0
Cerebral Edema	8/90 (8.9%)	8	10/88 (11.4%)	11
Headache	0/90 (0%)	0	1/88 (1.1%)	1
Dysphagia (Difficulty Swallowing)	4/90 (4.4%)	4	1/88 (1.1%)	1
Transient Ischemic Attack (TIA)	0/90 (0%)	0	2/88 (2.3%)	2
Hydrocephalus	0/90 (0%)	0	1/88 (1.1%)	1
IVH	0/90 (0%)	0	1/88 (1.1%)	1
SAH	5/90 (5.6%)	5	3/88 (3.4%)	3
ICH - HI -1	4/90 (4.4%)	4	0/88 (0%)	0
ICH - HI -2	1/90 (1.1%)	1	1/88 (1.1%)	1
ICH - PH1	5/90 (5.6%)	5	5/88 (5.7%)	5
ICH - PH2	3/90 (3.3%)	3	3/88 (3.4%)	3
Neurologic Decline	2/90 (2.2%)	2	5/88 (5.7%)	5
New Ischemic Stroke	0/90 (0%)	0	1/88 (1.1%)	1
Late ICH	2/90 (2.2%)	2	2/88 (2.3%)	2
Depression	1/90 (1.1%)	1	0/88 (0%)	0
Progression of index Stroke	6/90 (6.7%)	6	8/88 (9.1%)	8
Seizure - New Onset	1/90 (1.1%)	1	0/88 (0%)	0
Unresponsiveness	0/90 (0%)	0	1/88 (1.1%)	1
Renal and urinary disorders
Urinary Tract Infection	1/90 (1.1%)	1	1/88 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Hemoptysis (bloody sputum)	1/90 (1.1%)	1	0/88 (0%)	0
Pleural Effusion	0/90 (0%)	0	1/88 (1.1%)	1
Pneumonia	1/90 (1.1%)	1	2/88 (2.3%)	2
Pulmonary Emboli	0/90 (0%)	0	1/88 (1.1%)	1
Respiratory Arrest	1/90 (1.1%)	1	0/88 (0%)	0
Respiratory Distress	1/90 (1.1%)	1	7/88 (8%)	7
Respiratory Failure - Acute	13/90 (14.4%)	13	3/88 (3.4%)	3
Shortness of Breath	0/90 (0%)	0	1/88 (1.1%)	1
Tachypnea	0/90 (0%)	0	1/88 (1.1%)	1
Skin and subcutaneous tissue disorders
Other	0/90 (0%)	0	1/88 (1.1%)	1
Surgical and medical procedures
Access Site Complication	0/90 (0%)	0	2/88 (2.3%)	2
Intramural Arterial Dissection	1/90 (1.1%)	1	0/88 (0%)	0
Vascular disorders
Reocclusion at the site of original occlusion or proximal to original occlusion	1/90 (1.1%)	1	0/88 (0%)	0
Deep Vein Thrombosis (DVT)	1/90 (1.1%)	1	3/88 (3.4%)	3
Other (Not Including Serious) Adverse Events
	Merci Retriever		Trevo Stentriever
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/90 (81.1%)		71/88 (80.7%)
Blood and lymphatic system disorders
Anemia	17/90 (18.9%)	17	14/88 (15.9%)	14
Cardiac disorders
Arrhythmia - Tachycardia	4/90 (4.4%)	4	5/88 (5.7%)	5
Atrial Fibrillation	6/90 (6.7%)	6	9/88 (10.2%)	9
Gastrointestinal disorders
Constipation	5/90 (5.6%)	5	2/88 (2.3%)	2
Nausea and Vomiting (Non-Neuro)	3/90 (3.3%)	3	8/88 (9.1%)	8
General disorders
Fever	5/90 (5.6%)	5	4/88 (4.5%)	4
Positive Cultures	7/90 (7.8%)	7	3/88 (3.4%)	3
Metabolism and nutrition disorders
Hyperglycemia	10/90 (11.1%)	10	8/88 (9.1%)	8
Electrolyte Imbalance	24/90 (26.7%)	32	15/88 (17%)	22
Musculoskeletal and connective tissue disorders
Joint/Extremity Pain	10/90 (11.1%)	13	5/88 (5.7%)	5
Nervous system disorders
Cerebral Edema	8/90 (8.9%)	8	4/88 (4.5%)	4
Headache	8/90 (8.9%)	8	8/88 (9.1%)	9
Dysphagia (Difficulty Swallowing)	20/90 (22.2%)	20	14/88 (15.9%)	14
SAH	8/90 (8.9%)	8	1/88 (1.1%)	1
ICH - HI -1	7/90 (7.8%)	7	7/88 (8%)	7
ICH - PH1	8/90 (8.9%)	8	4/88 (4.5%)	4
Neurologic Decline	6/90 (6.7%)	6	0/88 (0%)	0
Renal and urinary disorders
Urinary Tract Infection	18/90 (20%)	19	14/88 (15.9%)	15
Hematuria	1/90 (1.1%)	2	6/88 (6.8%)	6
Urinary Retention	5/90 (5.6%)	5	3/88 (3.4%)	3
Respiratory, thoracic and mediastinal disorders
Pneumonia	21/90 (23.3%)	22	9/88 (10.2%)	10
Pulmonary Edema	5/90 (5.6%)	5	4/88 (4.5%)	4
Respiratory Failure - Acute	6/90 (6.7%)	6	3/88 (3.4%)	3
Vascular disorders
Deep Vein Thrombosis (DVT)	12/90 (13.3%)	12	9/88 (10.2%)	10

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.