Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04462536




Registration number
NCT04462536
Ethics application status
Date submitted
2/07/2020
Date registered
8/07/2020
Date last updated
11/09/2023

Titles & IDs
Public title
Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis
Scientific title
A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis
Secondary ID [1] 0 0
NA-1-009
Universal Trial Number (UTN)
Trial acronym
ESCAPE-NEXT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke, Acute 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Nerinetide

Placebo comparator: Placebo - Vehicle only

Experimental: Nerinetide - Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes


Treatment: Drugs: Placebo
Vehicle only

Treatment: Drugs: Nerinetide
Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with independent functioning on the modified Rankin Scale (mRS), as defined by a score of 0-2
Timepoint [1] 0 0
90 days
Secondary outcome [1] 0 0
Mortality rate, as defined by event rate (percent) for mortality over the 90-day study period.
Timepoint [1] 0 0
90 days
Secondary outcome [2] 0 0
Number of participants exhibiting a worsening of their index stroke.
Timepoint [2] 0 0
90 days
Secondary outcome [3] 0 0
A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the mRS at Day 90 post randomization.
Timepoint [3] 0 0
90 days
Secondary outcome [4] 0 0
Number of participants with good neurological outcome, as defined by a score of 0-2 on the NIHSS at Day 90 post randomization.
Timepoint [4] 0 0
90 days

Eligibility
Key inclusion criteria
1. Acute ischemic stroke (AIS) selected for emergency endovascular treatment.
2. Age 18 years or greater.
3. Onset (last-known-well) time to randomization time within 12 hours.
4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS):

1. NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA) occlusion; or
2. NIHSS > 10 for M2-MCA occlusion.
5. Confirmed symptomatic intracranial occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA. Tandem extracranial carotid and intracranial occlusions are permitted.
6. Pre-stroke (24 hours prior to stroke onset) independent functional status in activities of daily living with modified Barthel Index (BI) = 95. Patient must be living without requiring nursing care.
7. Qualifying imaging performed less than 2 hours prior to randomization.
8. Consent process completed as per national laws and regulation and the applicable ethics committee requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treated with a tissue plasminogen activator (e.g., alteplase or tenecteplase) within 24 hours before randomization.
2. Determination by the treating physician, based on current treatment guidelines and medical evidence, that treatment with a plasminogen activator is indicated.
3. Large core of established infarction defined as ASPECTS 0-4.
4. Absent or poor collateral circulation on qualifying imaging (e.g. collateral score of 0 or 1).
5. Any intracranial hemorrhage on the qualifying imaging.
6. Planned use of an endovascular device not having approval or clearance by the relevant regulatory authority.
7. Endovascular thrombectomy procedure is completed as defined by the presence of TICI 2c/3 reperfusion or completion of groin / arterial closure.
8. Clinical history, past imaging or clinical judgment suggesting that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
9. Estimated or known weight > 120 kg (264 lbs).
10. Pregnancy/Lactation; female, with positive urine or serum beta human chorionic gonadotropin (ß-hCG) test, or breastfeeding.
11. Known prior receipt of nerinetide for any reason, including prior enrolment in this ESCAPE-NEXT trial.
12. Severe known renal impairment defined as requiring renal replacement therapy (hemo- or peritoneal dialysis).
13. Severe or fatal comorbid illness that will prevent improvement or follow up.
14. Inability to complete follow-up treatment to Day 90.
15. Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding trial inclusion.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2023
Sample size
Target
Accrual to date
Final
850
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Gold Coast University Hospital - Gold Coast
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [6] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
- Gold Coast
Recruitment postcode(s) [5] 0 0
- Murdoch
Recruitment postcode(s) [6] 0 0
- Nedlands
Recruitment postcode(s) [7] 0 0
- Newcastle
Recruitment postcode(s) [8] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Rhode Island
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
State/province [18] 0 0
Nova Scotia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Canada
State/province [21] 0 0
Saskatchewan
Country [22] 0 0
Germany
State/province [22] 0 0
Aachen
Country [23] 0 0
Germany
State/province [23] 0 0
Altenburg
Country [24] 0 0
Germany
State/province [24] 0 0
Augsburg
Country [25] 0 0
Germany
State/province [25] 0 0
Bochum
Country [26] 0 0
Germany
State/province [26] 0 0
Bonn
Country [27] 0 0
Germany
State/province [27] 0 0
Dortmund
Country [28] 0 0
Germany
State/province [28] 0 0
Dresden
Country [29] 0 0
Germany
State/province [29] 0 0
Essen
Country [30] 0 0
Germany
State/province [30] 0 0
Frankfurt
Country [31] 0 0
Germany
State/province [31] 0 0
Freiburg
Country [32] 0 0
Germany
State/province [32] 0 0
Göttingen
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Heidelberg
Country [35] 0 0
Germany
State/province [35] 0 0
Kiel
Country [36] 0 0
Germany
State/province [36] 0 0
Leipzig
Country [37] 0 0
Germany
State/province [37] 0 0
München
Country [38] 0 0
Germany
State/province [38] 0 0
Münster
Country [39] 0 0
Germany
State/province [39] 0 0
Nürnberg
Country [40] 0 0
Germany
State/province [40] 0 0
Oldenburg
Country [41] 0 0
Germany
State/province [41] 0 0
Stuttgart
Country [42] 0 0
Germany
State/province [42] 0 0
Tübingen
Country [43] 0 0
Germany
State/province [43] 0 0
Würzburg
Country [44] 0 0
Italy
State/province [44] 0 0
Bologna
Country [45] 0 0
Italy
State/province [45] 0 0
Firenze
Country [46] 0 0
Italy
State/province [46] 0 0
Genoa
Country [47] 0 0
Italy
State/province [47] 0 0
Milan
Country [48] 0 0
Italy
State/province [48] 0 0
Napoli
Country [49] 0 0
Netherlands
State/province [49] 0 0
Amsterdam
Country [50] 0 0
Netherlands
State/province [50] 0 0
Maastricht
Country [51] 0 0
Netherlands
State/province [51] 0 0
Rotterdam
Country [52] 0 0
Norway
State/province [52] 0 0
Oslo
Country [53] 0 0
Norway
State/province [53] 0 0
Stavanger
Country [54] 0 0
Norway
State/province [54] 0 0
Tromsø
Country [55] 0 0
Singapore
State/province [55] 0 0
Singapore
Country [56] 0 0
Switzerland
State/province [56] 0 0
Aarau
Country [57] 0 0
Switzerland
State/province [57] 0 0
Basel
Country [58] 0 0
Switzerland
State/province [58] 0 0
Bern

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
NoNO Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Calgary
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael D. Hill, MD MSc
Address 0 0
Study Principal Investigator, University of Calgary
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04462536