Efficacy and Safety of Trans Sodium Crocetinate (TSC) for Treatment of Suspected Stroke (PHAST-TSC)

Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Efficacy and Safety of Trans Sodium Crocetinate (TSC) Administered Onboard Emergency Vehicles for Treatment of Suspected Stroke: PHAST-TSC

This study will assess the potential efficacy and safety of TSC as early treatment for both ischemic and hemorrhagic stroke when administered while subject is in ambulance being transported to hospital.

Study Overview

• Status: Terminated
• Conditions: Stroke, Acute
• Intervention / Treatment: Drug: Trans-Sodium Crocetinate; Other: Placebo

Detailed Description

This is a multicenter, randomized, placebo-controlled, double-blind, parallel group trial of intravenous trans sodium crocetinate (TSC) initiated by emergency medical service (EMS) responders in the field within 2 hours of symptom onset in 160 subjects with acute stroke. The primary objectives of the study are to evaluate the efficacy and safety of field-initiated TSC in improving the long-term functional outcome of subjects with acute stroke.

Subjects with acute stroke will be identified and screened in the ambulance by (EMS) responders who have received training in basic and advanced cardiac life support, stroke recognition, and specific procedures relevant to the proposed study. The EMS responders will contact a Study Neurologist, who will enroll eligible stroke patients into the study. Effort will be made to obtain prospective informed consent in the ambulance when deemed to be feasible. If not feasible, subjects will be enrolled under regulations for exception from explicit informed consent (EFIC) in emergency research circumstances, after public disclosure and community consultation. Written informed consent to continue in the study is obtained from subjects or their legally authorized representatives as soon as possible after hospital arrival.

EMS responders will deliver the single, field, bolus dose of study agent, TSC at 0.25 mg/kg or matched placebo, followed after hospital arrival by standard of care (SOC). No additional study drug will be administered in the hospital. Follow-up assessments will be performed at Emergency Department (ED) arrival, 24 hours, 48 hours, Day 4, Day 30, and Day 90. The study will be performed at up to 30 receiving hospital sites in Los Angeles County, CA, and central Virginia.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 40-85, inclusive
2. Last known well time 15-120 minutes before anticipated study drug injection
3. Suspected stroke identified by the LAPSS
4. Moderate to severe motor deficit, with Los Angeles Motor Scale (LAMS) 2 or higher
5. No seizure

Exclusion Criteria:

1. Coma
2. Rapidly improving neurologic deficit
3. History of seizures or epilepsy
4. Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound the neurological or functional outcome evaluations
5. SBP < 90 or > 220
6. Major head trauma in the last 24 hours
7. Recent stroke within 30 days
8. Known to be pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trans Sodium Crocetinate; Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.	Drug: Trans-Sodium Crocetinate; In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.; Other Names: TSC
Placebo Comparator: Placebo; The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.	Other: Placebo; The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Disability Level on the Modified Rankin Score (mRS)	Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes. 0 = No symptoms at all; = No significant disability despite symptoms; able to carry out all usual duties and activities; = Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; = Moderate disability; requiring some help, but able to walk without assistance; = Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; = Dead	90 days

Collaborators and Investigators

• Sponsor: Diffusion Pharmaceuticals Inc
• Collaborators: University of California, Los Angeles; University of Virginia
• Investigators: Principal Investigator: Andrew Southerland, MD, University of Virginia; Principal Investigator: Nerses Sanossian, MD, University of Southern California; Study Chair: Karen Johnston, MD, University of Virginia; Study Chair: Jeffrey Saver, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• Zachrison KS, Amati V, Schwamm LH, Yan Z, Nielsen V, Christie A, Reeves MJ, Sauser JP, Lomi A, Onnela JP. Influence of Hospital Characteristics on Hospital Transfer Destinations for Patients With Stroke. Circ Cardiovasc Qual Outcomes. 2022 May;15(5):e008269. doi: 10.1161/CIRCOUTCOMES.121.008269. Epub 2022 Apr 4.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2019
• Primary Completion (Actual): October 19, 2020
• Study Completion (Actual): October 19, 2020

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Trans-sodium crocetinate
• Other Study ID Numbers: 100-501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No