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
The Frontier Trial – Field Randomization of NA-1 Treatment In Early Responders
A stroke is a brain attack. A stroke is caused by a sudden blockage of a blood vessel supplying the brain (ischemic), or bleeding into or around the brain (hemorrhagic). Most strokes (85%) are ischemic. Stroke should be treated as a medical emergency because there is a critical time, a “therapeutic window”, which may vary from minutes to a few hours in which a stroke can be reversed or mitigated. Acute ischemic stroke can be treated with medicines to unblock the artery and with urgent surgery to unblock the artery. Both are highly time sensitive treatments. The phrase “time is brain” emphasizes that brain tissue is rapidly and irretrievably lost as stroke progresses and that early intervention is critical to improve a stroke victim's outcome. Medicines that could slow or halt the progression of damage to the brain after a brain artery is blocked could substantially benefit patients. This what NA-1 does. NA-1 is being developed as an emergency drug aimed at reducing global disability in patients with acute cerebral ischemia if administered within three hours of symptom onset.
The main goal of the study is to determine the efficacy of NA-1 in reducing global disability in patients with acute stroke.
Other goals of the study are to determine the efficacy of NA-1 in:
- Reducing functional dependence.
- Improving neurological outcome.
- Increasing the proportion of aborted strokes.
- Improving activities of daily living.
Study Design and Setting:
This trial is a multicenter, randomized, double-blind, placebo-controlled, single dose study initiated prehospital in the ambulance. It is being conducted using the Emergency Medical Services (EMS) of Toronto and Peel Region, ON and Vancouver, BC, Canada, as well as one U.S. jurisdiction. Subjects with suspected acute stroke will be identified in the field by licensed, trained paramedics using the approved stroke protocol in use by the local EMS system and further screened with components of the modified Los Angeles Prehospital Stroke Scale (mLAPSS) to increase sensitivity of identifying likely stroke patients. Stroke severity will be graded by the Los Angeles Motor Scale (LAMS) and then approved for the study by an on-call physician-investigator by cellular phone. The paramedics will then begin study drug administration. Upon arrival at the emergency department (ED), subjects will receive standard-of-care treatment, including thrombolytic or endovascular therapy, as appropriate.
Study Sample Size:
A total of 558 subjects with suspected acute stroke, who meet the criteria used by participating EMS for urgent transport to a stroke center, between the ages of 40-95 years, weighing between 45-120 kg, and with a neurological deficit present for ≥ 15 minutes will be randomized in this study within three hours of symptom onset.
We are set to begin recruitment for the study in March 2015.
Study website: www.frontiertrial.com or www.frontiertrial.ca
Study Sponsor: http://www.nonoinc.ca/page2/page2.html
More information on this study can be found at the following links:
Heart and Stroke Foundation 2015 Stroke Report
Heart and stroke
This study has been registered on clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT02315443
Frequently Ask Questions:
What is the Frontier Study?
Currently, paramedics use a provincial stroke protocol to identify eligible patients and transport them to a stroke care centre. All stroke patients will continue to receive the current standard of care. In addition, the FRONTIER study is designed to examine whether a drug known as NA-1 will minimize the impact of a stroke when given by paramedics. Once in hospital, patients will continue to receive standard stroke care.
The study involves paramedics of Peel, Toronto and Vancouver as well as stroke centres at St. Michael’s Hospital, Sunnybrook Health Sciences Centre, Toronto Western Hospital, Trillium Health Partners - Mississauga Hospital and Vancouver General Hospital. It is supported by a Multi-Investigator Research Initiative grant from the Brain Canada Foundation and sponsored by NoNO Inc.
How and why did Peel and Toronto Regional Paramedic Services and British Columbia Emergency Health Services become involved in the study?
Research is an important driver of any medical advancement. As key partners in emergency care, paramedic involvement in research is one way that we deliver on our community commitment to promote safety, decrease suffering and save lives.
What’s involved in being part of a study like this?
It takes a team of dedicated people to bring the idea of a study like this to life. Our education and research staff has been working with everyone from the researchers, drug developers, our logistics department and our management and frontline paramedics to manage all the educational and logistical requirements that need to happen so that eligible stroke patients are enrolled into this study.
Why are you administering a drug without patient consent?
Stroke kills two million brain cells per minute. Given the immediate nature of emergency stroke care, Health Canada and the Research Ethics Boards at the centres participating in this trial have deferred consent to the in-hospital setting once the medical emergency is under control.
How will I know if I’ve been enrolled in the trial?
Patients enrolled in the study will receive a follow up visit by hospital staff within 48 hours of their arrival in hospital. For more information, please see how Study Overview section.
What are the side effects of this drug?
With any drug there are side effects. Studies to date have shown no long-term side effects; minor side effects of the drug have included symptoms such as headache, nausea, vomiting and lowering of the blood pressure which resolve with usual care.
If I’m having a stroke, can I request or refuse the drug?
In an emergency like a stroke, time is critical. Paramedics assess patients to be able to provide stroke care which may or may not include enrolling a patient into this study. Patients have the right to refuse medical care including participation in the study at any point during treatment.
Why was my dad taken to a stroke centre, but not enrolled in the study?
All stroke patients who meet the provincial stroke protocol are taken to a Regional stroke centre. In order to determine whether the drug NA-1 is effective, only patients who meet the additional study criteria.
For more information please contact the Rescu research study group at 1-888-707-3015.