Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of NA-1 in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) (ESCAPE-NA1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02930018
Recruitment Status : Recruiting
First Posted : October 11, 2016
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
University of Calgary
Information provided by (Responsible Party):
NoNO Inc.

Brief Summary:
The ESCAPE-NA-1 study is designed to determine the safety and efficacy of the neuroprotectant, NA-1, in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation who are selected for endovascular revascularization.

Condition or disease Intervention/treatment Phase
Stroke, Acute Drug: NA-1, 2.6 mg/kg Drug: Placebo Phase 3

Detailed Description:

Trial Objectives:

The primary objective is to determine the efficacy of the neuroprotectant, NA-1, in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation selected for rapid endovascular revascularization.

The secondary objectives are to determine the efficacy of NA-1 in:

  • Reducing functional dependence
  • Improving neurological outcome
  • Improving activities of daily living
  • Reducing mortality rate The leading safety objectives are to determine the effect of administering a dose of 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous (IV) infusion of NA-1 to subject with acute stroke who are selected for endovascular revascularization on serious adverse events (SAEs) and 90-day mortality.

Trial Design:

This study is a Phase 3, randomized, multicentre, blinded, placebo-controlled, parallel group, single-dose design. Subjects harboring an acute ischemic stroke and who are selected for endovascular revascularization in accordance with local institutional practices and who harbor a small established infarct core and with good collateral circulation will be given a single, 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous dose of NA-1 or placebo as soon as they are deemed to have met the enrollment criteria and with the intention of starting administration within 30 minutes of randomization. The randomization will be by stochastic minimization to balance baseline factors.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Placebo Comparator: Placebo
Drug vehicle only
Drug: Placebo
Placebo Comparator: Placebo
Other Name: Drug vehicle only

Experimental: NA-1, 2.6 mg/kg
Single intravenous infusion of NA-1 over 10 ± 1 minutes
Drug: NA-1, 2.6 mg/kg
Single intravenous infusion of NA-1 over 10 ± 1 minutes
Other Name: Tat-NR2B9c




Primary Outcome Measures :
  1. Modified Rankin Score (mRS) [ Time Frame: 90 Days ]
    Overall proportion of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS


Secondary Outcome Measures :
  1. mRS Shift Analysis [ Time Frame: 90 Days or the last rating ]
    Shift of one or more categories to reduced functional dependence analyzed across the whole distribution of scores on the mRS at Day 90 or the last rating.

  2. NIHSS [ Time Frame: 90 Days or the last rating ]
    Proportion of subjects with good neurological outcome, as defined by a score of 0-2 on the NIHSS at Day 90 or the last rating.

  3. Barthel Index [ Time Frame: 90 Days or the last rating ]
    Proportion of subjects with functional independence in activities of daily living, as defined by a score of ≥ 95 on the BI at Day 90 or the last rating.

  4. Mortality Rate [ Time Frame: 90 Days ]
    A reduction in mortality rate, as defined by event rate (%) for mortality over the 90-day study period

  5. Functional Independence based on mRS [ Time Frame: 90 Days or the last rating ]
    Proportion of subjects with functional independence, as defined by a score of 0-1 on the mRS at Day 90 or the last rating.


Other Outcome Measures:
  1. EQ-5D-5L [ Time Frame: 90 Days or the last rating ]
    Health-related quality of life, as measured by the EQ-5D-5L at Day 90 or the last rating.

  2. Stroke Volume [ Time Frame: 24 hour follow up ]
    Volume of stroke as measured by MRI. If NCCT was done instead of MRI, Volume of stroke will be derived from hypodense areas.

  3. Test of language function [ Time Frame: 90 Days ]
    Cognitive outcome - The 15-item Boston Naming Test (BNT15)

  4. Test of hemi-spatial neglect [ Time Frame: 90 Days ]
    Cognitive Outcome - Sunnybrook hemi-spatial neglect procedure (SNAP)

  5. Global test of cognitive function. Scale from 0 to 30 points. [ Time Frame: 90 Days ]
    Cognitive outcome - The Montreal Cognitive Assessment (MoCA)

  6. Functional outcome based on mRS [ Time Frame: 30 days ]
    The proportion of subjects experiencing a favorable functional outcome 30 days post-randomization, defined as 0 to 2 on the mRS.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute ischemic stroke (AIS) for immediate endovascular treatment
  2. Age 18 or greater.
  3. Onset (last-seen-well) time to randomization time within 12 hours.
  4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS) > 5 at the time of randomization.
  5. Pre-stroke (24 hours prior to stroke onset) independent functional status in activities of daily living with modified Barthel Index (BI) > 90 (95 or 100). Patient must be living in their own home, apartment or seniors lodge where no nursing care is required.
  6. Confirmed symptomatic intracranial occlusion, based on multiphase or dynamic computerized tomographic angiography (CTA), at one or more of the following locations: Intracranial carotid T/L, M1 middle cerebral artery (MCA). Functionally, when defining the M1 or the M2, the bulk of the MCA territory must be ischemic.
  7. Non-contrast computed tomography (NCCT) and CTA (multiphase or dynamic) for trial eligibility performed or repeated at ESCAPE-NA1 stroke centre with endovascular suite on-site.
  8. Endovascular treatment with declared first endovascular approach as either stent retriever or aspiration device, and intended to be initiated (arterial access) within 60 minutes of baseline/qualifying NCCT and to first recanalization of 90 minutes. Study drug intended to be administered within 60 minutes of the baseline/qualifying NCCT.
  9. Signed informed consent from subject or legally authorized representative or, if required to enable inclusion by applicable national laws and regulations and the applicable independent review boards/Ethics Committee requirements for obtaining consent, from the investigator after consultation with an independent physician who is not otherwise participating in the trial.

Exclusion Criteria:

  1. Evidence of a large core of established infarction defined as ASPECTS 0-4.
  2. Evidence of absence of collateral circulation on CTA (Collateral score of 0 or 1).
  3. Intent to use any endovascular device other than a stent retriever or clot aspiration device or intra-arterial medications as the initial thrombectomy approach.
  4. Intent to use any intravenous thrombolytic other than alteplase if intravenous thrombolysis is planned.
  5. No femoral pulses, very difficult endovascular access or extreme tortuosity of great vessels that is predicted to result in an inability to deliver timely endovascular therapy. Direct common carotid or radial/brachial/axillary access is permissible.
  6. Estimated or known weight > 120 kg or < 45 kg.
  7. Pregnancy; if a woman is of childbearing potential a urine or serum beta human chorionic gonadotropin (β-hCG) test is positive, or breastfeeding.
  8. Severe contrast allergy or absolute contraindication to iodinated contrast preventing endovascular intervention, including any contraindications listed in the prescribing information approved by local authorities (e.g., patients with decompensated heart failure as a contraindication for the use of VISIPAQUE™ 270 in Germany).
  9. Clinical history, past imaging or clinical judgment suggests that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
  10. Prior enrolment in the ESCAPE-NA1 trial or prior receipt of NA-1 for any reason.
  11. Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or if known a creatinine clearance < 29 mL/min.
  12. Patient has a severe or fatal comorbid illness that will prevent improvement or follow-up.
  13. Patient cannot complete follow-up treatment due to co-morbid non-fatal illness or they are known to be a visitor to the city or any other known reason for which follow-up would be impossible (e.g. incarcerated in a federal prison).
  14. Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding study inclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02930018


Contacts
Layout table for location contacts
Contact: Michael Tymianski, MD PhD 416-603-5899 mtymianski@nonoinc.ca
Contact: Kathy Heard, MSc 416-603-5481 kheard@nonoinc.ca

  Hide Study Locations
Locations
Layout table for location information
United States, California
Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Sidney Starkman, MD         
California Pacific Medical Center - Davies Campus Active, not recruiting
San Francisco, California, United States, 94114
Providence Little Company of Mary Medical Center Torrance Recruiting
Torrance, California, United States, 90503
Contact: Jason Tarpley, MD         
United States, Colorado
Swedish Medical Center Recruiting
Englewood, Colorado, United States, 80110
Contact: Donald Frei, MD         
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Joseph Schindler, MD         
United States, Florida
Baptist Health Medical Center Recruiting
Jacksonville, Florida, United States, 32207
Contact: Eric Sauvageau, MD         
United States, Georgia
Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
Contact: Raul Noguiera, MD         
WellStar Health Systems Recruiting
Marietta, Georgia, United States, 30060
Contact: Rishi Gupta, MD         
United States, Illinois
Rush University Medical Center Completed
Chicago, Illinois, United States, 60612
United States, Massachusetts
University of Massachusetts Medical School Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Ajit Puri, MD         
United States, Missouri
Saint Luke's Hospital of Kansas City Recruiting
Kansas City, Missouri, United States, 64111
Contact: Coleman Martin, MD         
United States, New York
NYU Lutheran Medical Center Recruiting
Brooklyn, New York, United States, 11220
Contact: David Turkel-Parrella, MD         
United States, North Carolina
Novant Health Forsyth Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27103
Contact: Don Heck         
United States, Ohio
Riverside Radiology Recruiting
Columbus, Ohio, United States, 43214
Contact: Ronald Budzik, MD         
United States, Pennsylvania
Abington Memorial Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19001
Contact: Hana Choe, MD         
UPMC Presbyterian Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Ashutosh Jadhav, MD         
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Ryan McTaggart         
United States, Tennessee
Chattanooga Center for Neurologic Research Recruiting
Chattanooga, Tennessee, United States, 37403
Contact: Ruchir Shah         
United States, Texas
Valley Baptist Medical Center Not yet recruiting
Harlingen, Texas, United States, 78550
Contact: Ameer Hassan         
United States, Washington
Swedish Medical Center- Cherry Hill Campus Active, not recruiting
Seattle, Washington, United States, 98122
Australia
Royal Adelaide Hospital Recruiting
Adelaide, Australia
Contact: Timothy Kleinig, MD         
Royal Melbourne Hospital Recruiting
Parkville, Australia
Contact: Bruce Campbell, MD       Bruce.Campbell@mh.org.au   
Canada, Alberta
University of Calgary - Foothills Medical Centre Recruiting
Calgary, Alberta, Canada, T2N2T9
Contact: Andrew M Demchuk, MD       ademchuk@ucalgary.ca   
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Brian Buck, MD         
Canada, British Columbia
Vancouver Stroke Program Research Office/ Vancouver General Hosptial Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Thalia Field, MD         
Canada, Nova Scotia
Queen Elizabeth II Health Science Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Contact: Stephen Phillips, MD         
Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Demetrios Sahlas, MD         
London Health Sciences Centre- University Hospital Recruiting
London, Ontario, Canada, N6A 5A5
Contact: Jennifer Mandzia, MD         
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1Y 4E9
Contact: Dar Dowlatshahi, MD         
Sunnybrook Health Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Richard Swartz, MD         
St Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Daniel Selchen, MD         
University Health Network - Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Frank Silver, MD         
Canada, Quebec
CHUM Hopital Notre-Dame Recruiting
Montréal, Quebec, Canada, H2L 4M1
Contact: Alexandre Poppe, MD         
Montreal Neurological Institute and Hospital Recruiting
Montréal, Quebec, Canada, H3A1A1
Contact: Jeanne Teitelbaum, MD         
CHU de Quebec- Universite Laval- Hopital de l'Enfant-Jesus Recruiting
Quebec City, Quebec, Canada, G1J 1Z4
Contact: Marie-Christine Camden, MD         
Canada, Saskatchewan
Royal University Hospital Recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Contact: Michael Kelly, MD         
Germany
Universitätsklinikum Carl Gustav Carus Dresdner Neurovaskulares Centrum Recruiting
Dresden, Germany, 01307
Contact: Volker Puetz, MD         
Klinik für Radiologie und Neuroradiologie Recruiting
Essen, Germany, D - 45131
Contact: Rene Chapot         
University Medical Center Goettingen Recruiting
Göttingen, Germany, 37075
Contact: Marios Psychogios, MD         
Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany
Contact: Götz Thomalla, MD       thomalla@uke.de   
Neurologische Klinik, Universität Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Simon Nagel         
Ireland
Beaumont Hospital Recruiting
Dublin, Ireland
Contact: John Thornton, MD       johnthornton@beaumont.ie   
Mater Hospital Recruiting
Dublin, Ireland
Contact: Seán Murphy, MD         
Korea, Republic of
Dongsan Medical Centre Active, not recruiting
Daegu, Korea, Republic of
Inha University Hospital Recruiting
Incheon, Korea, Republic of
Contact: Joung-Ho Rha, MD         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Oh-Young Bang, MD         
Yonsei Univ, Severence Recruiting
Seoul, Korea, Republic of
Contact: Ji-Hoe Heo, MD         
Sweden
Skåne University Hospital Active, not recruiting
Lund, Sweden
Karolinksa Institutet Active, not recruiting
Stockholm, Sweden, 17176
United Kingdom
Royal Victoria Hospital Recruiting
Belfast, United Kingdom
Contact: Paul Burns, MD       paul.burns@belfasttrust.hscni.net   
Sponsors and Collaborators
NoNO Inc.
University of Calgary
Investigators
Layout table for investigator information
Principal Investigator: Michael D Hill, MD MSc University of Calgary

Publications:

Layout table for additonal information
Responsible Party: NoNO Inc.
ClinicalTrials.gov Identifier: NCT02930018     History of Changes
Other Study ID Numbers: NA-1-007
First Posted: October 11, 2016    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NoNO Inc.:
Acute Ischemic Stroke
Endovascular Thrombectomy
Neuroprotection
Tat-NR2B9c
NA-1

Additional relevant MeSH terms:
Layout table for MeSH terms
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases