Direct-to-angio Approach From loCal hOspitals Based on a PoInt-of-care bLOod Test for LVO

Official title

Direct-to-angio Approach From loCal hOspitals Based on a PoInt-of-care bLOod Test for LVO (COPILOT): an Effectiveness Cluster Randomized Crossover Trial

Overview

Direct-to-angio approach from loCal hOspitals based on a PoInt-of-care bLOod Test for LVO (COPILOT) is a multi-center, prospective, cluster-randomized crossover trial that will evaluate if the triage assessment to thrombectomy puncture time is shorter after performing the LVOne testing compared to current management standards in patients with suspected large vessel occlusion.

Detailed description

The COPILOT trial utilizes a cluster randomized crossover design within the Sistema de Salud Menonita (SSM) hospital network to evaluate if early detection of large vessel occlusion (LVO) stroke with a novel blood test can accelerate the time from triage assessment to thrombectomy puncture. It will unfold in three phases:

Phase 0 - Baseline Data Collection (3 months): Before the random allocation, all clusters undergo data collection on baseline characteristics and outcome measures to confirm/set a pre-intervention comparison ground. Phase 0 patients will receive the current standard of care. An interim analysis will check recruitment rates and explore the need for additional clusters for adequate study power.

Phase 1 - Intervention and Control (12 months): Clusters are randomized to either the intervention or control group, with the intervention arm implementing the LVOne test and the control arm continuing standard care without the LVOne test. Data analysts remain blinded to group allocation, while an interim analysis revisits recruitment and primary outcomes to assess whether additional clusters are required.

Phase 2 - Crossover (12 months): Clusters switch roles from Phase 1, allowing every cluster to experience both the intervention and control conditions, facilitating within-cluster comparisons. The nature of the intervention prevents the blinding of participants and staff.

Interventions

• Diagnostic test Diagnostic standard of care
  Participants will receive the diagnostic standard of care: standard laboratory workup, non-contrast brain CT, brain CTA, brain CTP, or brain MRI.
• Diagnostic test LVOne Test
  Participants will receive the LVOne test, which will measure D-dimer and Glial Fibrillary Acidic Protein (GFAP) levels to diagnose acute stroke.

Primary outcome measures

• Change in the time from triage assessment to thrombectomy puncture [Time frame: 24 hours]

Secondary outcome measures (9)

• Time from spoke hospital triage assessment to LVOne test in intervention [Time frame: 24 hours]
• Time from HUB hospital triage assessment to LVOne test in intervention [Time frame: 24 hours]
• Time from HUB hospital triage assessment to thrombectomy puncture [Time frame: 24 hours]
• Thrombectomy rate (proportion of treated LVO) [Time frame: 24 hours]
• Length of hospital stay [Time frame: From date of randomization until the date of discharge or date of death from any cause while patient is in hospital, whichever came first, assessed up to 30 days]
• Length of ICU stay [Time frame: From date of randomization until the date of discharge or date of death from any cause while patient is in hospital, whichever came first, assessed up to 30 days]
• Diagnostic accuracy for LVO detection [Time frame: At the time of initial assessment and confirmed by diagnostic imaging within 24 hours]
• Diagnostic accuracy for intracerebral hemorrhage detection [Time frame: At the time of initial assessment and confirmed by diagnostic imaging within 24 hours]
• Modified Rankin Scale (mRS) [Time frame: At the time of initial assessment, 24 hours, at discharge, 3 months, 6 months, and 12 months]

Eligibility criteria

Inclusion criteria

• Age: 21 to 85 years old
• Language: Speak and understand Spanish or English
• Residence: Resident of Puerto Rico
• Clinical presentation: Suspected acute stroke
• Time of presentation: Monday to Friday, between 8:00 a.m. and 4:00 p.m.
• Time of symptom onset: symptoms are known to have begun within the last 6 hours, OR last known to be well between 6 and 18 hours ago, confirmed by a reliable witness or healthcare professional

Exclusion criteria

• Previous healthcare encounter:
• Already assessed at another hospital, and ambulance admission is a transfer for continuing care OR
• Received thrombolysis therapy before consent (e.g., tPA, alteplase)
• Medical History: diagnosed with any of the following in the past 4 weeks: deep vein thrombosis (DVT), pulmonary embolism (PE), arterial embolism, stroke, transient ischemic attack (TIA), long bone fracture, major trauma, surgery under general anesthesia, or head injury requiring hospital admission within the last 4 weeks.
• Modified Rankin Scale: Pre-stroke mRS ≥ 3
• The patient is a pregnant woman
• The patient is under legal custody or deprived of liberty in penitentiary institutions
• The patient is unable to provide informed consent on their own and whose authorized legal representatives are unavailable in person or by telephone during recruitment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Diagnostic

Study locations

Puerto Rico · 1 center

• Hospital Menonita Caguas — Caguas

Publications

• Malhotra K, Gornbein J, Saver JL. Ischemic Strokes Due to Large-Vessel Occlusions Contribute Disproportionately to Stroke-Related Dependence and Death: A Review. Front Neurol. 2017 Nov 30;8:651. doi: 10.3389/fneur.2017.00651. eCollection 2017. PMID 29250029
• Victor P, Bian E, Mamdouh H, Mohamed GA, Nour HA, Miller K, Singh K, Patel S, Segovis C, Nahab F. Upfront vascular imaging in acute stroke: Impact on thrombectomy transfer time at a primary stroke center. J Stroke Cerebrovasc Dis. 2024 Aug;33(8):107815. doi: 10.1016/j.jstrokecerebrovasdis.2024.107815. Epub 2024 Jun 13. PMID 38878844
• Saver JL. Time is brain--quantified. Stroke. 2006 Jan;37(1):263-6. doi: 10.1161/01.STR.0000196957.55928.ab. Epub 2005 Dec 8. PMID 16339467
• Durrani Y, Gerstl JVE, Murphy D, Harris A, Saali I, Gropen T, Shekhar S, Kappel AD, Patel NJ, Du R, Guardia REA, Vicenty-Padilla JC, Dmytriw AA, Pereira VM, Izzy S, Khan A, Aziz-Sultan MA, Liebeskind DS, Davies JM, Siddiqui AH, Gaude E, Bernstock JD. Prospective Validation of Glial Fibrillary Acidic Protein, d-Dimer, and Clinical Scales for Acute Large-Vessel Occlusion Ischemic Stroke Detection. S PMID 41585381
• Gaude E, Nogueira B, Ladreda Mochales M, Graham S, Smith S, Shaw L, Graziadio S, Ladreda Mochales G, Sloan P, Bernstock JD, Shekhar S, Gropen TI, Price CI. A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes. Diagnostics (Basel). 2021 Jun 22;11(7):1137. doi: 10.3390/diagnostics11071137. PMID 34206615
• Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, Khoury J. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996 Aug;27(8):1304-5. doi: 10.1161/01.str.27.8.1304. PMID 8711791
• Puetz V, Dzialowski I, Hill MD, Subramaniam S, Sylaja PN, Krol A, O'Reilly C, Hudon ME, Hu WY, Coutts SB, Barber PA, Watson T, Roy J, Demchuk AM; Calgary CTA Study Group. Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score. Int J Stroke. 2008 Nov;3(4):230-6. doi: 10.1111/j.1747-4949.2008.00221.x. PMID 18811738
• Bamford J. Clinical examination in diagnosis and subclassification of stroke. Lancet. 1992 Feb 15;339(8790):400-2. doi: 10.1016/0140-6736(92)90085-h. No abstract available. PMID 1346666

Identifiers

NCT: NCT06910163 · 2410303013

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗