Clinical trial NCT02315443: Field Randomization of Nerinetide (NA-1) Therapy in Early Responders
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Intravenous NA-1 Initiated by Paramedics in the Field for Acute Cerebral Ischemia Within Three Hours of Symptom Onset
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Cerebral Ischemia
Keywords: Stroke
Ischemia
Prehospital
NA-1
Modified Rankin Scale
Haemorrhagic stroke
Transient ischemic attack
Nerinetide
Lead sponsor: NoNO Inc.
Sponsor class: INDUSTRY
Collaborators: name: Brain Canada
name: Djavad Mowafaghian Centre for Brain Health
name: Canadian Stroke Network
name: University of Calgary
name: University of Toronto
name: University of British Columbia
name: Genome British Columbia
First posted: 2014-12-11
Enrollment: 532
Sex: ALL
Minimum age (years): 40
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether nerinetide (NA-1) is effective in reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset.

Detailed description: Nerinetide (NA-1) is being developed as an emergency drug aimed at reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset.

The primary objective is to determine the efficacy of nerinetide in reducing global disability in patients with acute stroke. The secondary objectives are to determine the efficacy of nerinetide in reducing functional dependence, reducing mortality rate, reducing worsening of stroke, improving neurological outcome and improving activities of daily living.

The leading safety objectives are to determine the effect of administering a target dose of 2.60 mg/kg (up to a maximum dose of 270 mg) IV infusion of nerinetide within three hours of symptom onset by paramedics in the field on serious adverse events and 90-day mortality.

This trial is a multicenter, randomized, double-blind, placebo-controlled, single dose study initiated prehospital in the ambulance. It is being conducted using Emergency Medical Services (EMS) in Canada. Subjects with suspected acute stroke will be identified in the field by trained paramedics using the approved stroke protocol in use by the local EMS system, and further screened for eligibility and approval by an on-call trial physician. The paramedics will administer the study drug. Upon arrival at the emergency department, subjects will receive standard-of-care.

An Independent Data Monitoring Committee will perform safety reviews of the clinical data.

Eligibility criteria: Inclusion Criteria:

* Provisional diagnosis of acute stroke as identified by paramedics using the local stroke triage tool
* Respiratory rate 12-24 breaths per minute
* Oxygen saturation ≥ 90% on room air
* Systolic blood pressure \< 90 or \> 220 mmHg
* Weight 45-120 kg
* Last seen in usual state of health less than 3 hours before anticipated study drug initiation
* Independently ambulatory with or without devices prior to event
* LAMS score of 2-5 for at least 15 minutes and remains 2-5 at time of randomization

Exclusion Criteria:

* Lack of IV access
* Canadian Triage and Acuity Scale Level 1 and/or uncorrected airway, breathing or significant circulatory problem
* Blood sugar \< 3 mmol/L (\< 55 mg/dL)
* Seizure at onset of symptoms or observed by paramedic
* Glasgow coma score of \<10
* Major head trauma in the last three months
* Recent stroke in the last three months
* Known or presumptive signs of pregnancy or breastfeeding
* Prisoner
* Long term care facility resident
* Known advance directive to not resuscitate
* Known participation in a clinical trial with an investigational drug or device within 30 days preceding this trial
* Pre-existing neurologic, psychiatric, or advanced systemic condition that would preclude obtaining the neurological or functional outcome evaluations

Primary outcomes:
measure: Modified Rankin Scale (mRS) scale
timeFrame: 90 days
Secondary outcomes:
measure: mRS shift analysis
timeFrame: 90 Days or the last rating
measure: Mortality rate
timeFrame: 90 Days
measure: Worsening of stroke rate
timeFrame: 90 Days
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 90 Days or the last rating
measure: Barthel Index
timeFrame: 90 Days or the last rating
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Ambulance Service and British Columbia Emergency Health Services
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital, Vancouver Coastal Health
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Jim Christenson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Richard Swartz, M.D.
role: PRINCIPAL_INVESTIGATOR
References: