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

• Sponsor: Diffusion Pharmaceuticals Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03763929
• Collaborator: University of California, Los Angeles (Other), University of Virginia (Other)
• Enrollment: 6
• Locations: 2
• Arms: 2
• Actual Duration (Months): 13.9
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke, Acute	Drug: Trans-Sodium Crocetinate; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter, randomized, placebo-controlled, double-blind, parallel groupMulticenter, randomized, placebo-controlled, double-blind, parallel group
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: TSC injections will be prepared and injected by unblinded personnel on each ambulance. All other study personnel will be blinded
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 22, 2019
• Actual Primary Completion Date: Oct 19, 2020
• Actual Study Completion Date: Oct 19, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Global Disability Level on the Modified Rankin Score (mRS) [90 days]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	University of Virginia	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• Diffusion Pharmaceuticals Inc
• 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

Study Documents (Full-Text)

• Study Protocol - Nov 18, 2019

More Information

Publications

None provided.

• Responsible Party: Diffusion Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT03763929
• Other Study ID Numbers: 100-501
• First Posted: Dec 4, 2018
• Last Update Posted: Jun 18, 2021
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Stroke; Trans-sodium crocetinate

Study Results

Participant Flow

Arm/Group Title	Trans Sodium Crocetinate	Placebo
Arm/Group Description	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. 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.	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. Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.
Period Title: Overall Study
STARTED	2	4
COMPLETED	2	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Trans Sodium Crocetinate	Placebo	Total
Arm/Group Description	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. 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.	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. Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.	Total of all reporting groups
Overall Participants	2	4	6
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	74.0	63.8	67.2
Sex: Female, Male (Count of Participants)
Female	1 50%	2 50%	3 50%
Male	1 50%	2 50%	3 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 25%	1 16.7%
Not Hispanic or Latino	2 100%	3 75%	5 83.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 25%	1 16.7%
White	2 100%	3 75%	5 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	4 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Global Disability Level on the Modified Rankin Score (mRS)
Description	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
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Trans Sodium Crocetinate	Placebo
Arm/Group Description	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. 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.	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. Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.
Measure Participants	2	3
Median (Full Range) [score on a scale]	2.5	3.0

Adverse Events

Time Frame	Adverse event data were collected from the start of study drug administration through the end of the Day 90 follow-up visit.
Arm/Group Title	Trans Sodium Crocetinate		Placebo
Arm/Group Description	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. 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.		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. Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.
All Cause Mortality
	Trans Sodium Crocetinate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		1/4 (25%)
Serious Adverse Events
	Trans Sodium Crocetinate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/4 (50%)
Infections and infestations
Pneumonia	0/2 (0%)	0	1/4 (25%)	1
Nervous system disorders
Hemorrhagic Transformation of Infarct	1/2 (50%)	1	0/4 (0%)	0
Cerebral Edema	0/2 (0%)	0	2/4 (50%)	2
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	0/2 (0%)	0	1/4 (25%)	1
Vascular disorders
Hypotension	0/2 (0%)	0	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Trans Sodium Crocetinate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		4/4 (100%)
Blood and lymphatic system disorders
Hypochromic Anemia	0/2 (0%)	0	1/4 (25%)	1
Gastrointestinal disorders
Constipation	0/2 (0%)	0	2/4 (50%)	2
Nausea	0/2 (0%)	0	1/4 (25%)	1
General disorders
Pain	0/2 (0%)	0	1/4 (25%)	1
Pyrexia	0/2 (0%)	0	1/4 (25%)	1
Injury, poisoning and procedural complications
Ankle Fracture	0/2 (0%)	0	1/4 (25%)	1
Fall	0/2 (0%)	0	1/4 (25%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/2 (0%)	0	2/4 (50%)	2
Nervous system disorders
Headache	0/2 (0%)	0	1/4 (25%)	1
Hemiparesis	0/2 (0%)	0	1/4 (25%)	1
Psychiatric disorders
Agitation	0/2 (0%)	0	1/4 (25%)	1
Anxiety	0/2 (0%)	0	1/4 (25%)	1
Renal and urinary disorders
Urinary Retention	1/2 (50%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/2 (0%)	0	1/4 (25%)	1
Increased Bronchial Secretion	0/2 (0%)	0	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Pruritis	0/2 (0%)	0	1/4 (25%)	1

Limitations/Caveats

The trial was early terminated after 6 subjects were enrolled due to logistical issues surrounding the COVID-19 pandemic. Due to this low enrollment number, the statistical plan outlined in the protocol was not utilized. Data listings and tables were instead created, which captured data on the 6 subjects in a descriptive manner. Therefore, no substantive conclusions could be drawn.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.