Exertional Heat Stroke
Conditions
Brief summary
A double-blind, parallel study of Ryanodex for the adjuvant treatment of exertional heat stroke (EHS) compared to current Standard of Care (SOC) for EHS.
Detailed description
Following triage and primary assessment in the emergency medical facility, subjects will be randomized to 1 of 2 treatment arms, SOC plus Ryanodex or SOC only. Subjects will be dosed and followed for up to 6 hours post-randomization. Current SOC is limited to body cooling and supportive measures.
Interventions
DRUGRyanodex and Standard of Care
Ryanodex to be administered as a rapid IV push
OTHERStandard of Care
Body cooling measures and supportive measures
Sponsors
Eagle Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
Ryanodex (dantrolene sodium) for injectable suspension plus Standard of Care
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Core body temperature of greater than or equal to 40.0 degrees C (104 degrees F); recent history of exertional activity; GCS score less than 13; tachycardia -
Exclusion criteria
clinical severe infection; hyperthermia secondary to another condition; endotracheal intubation;; sedative drugs administered prior to or at time of study entry; likelihood of head trauma within 6 months pre-study; positive pregnancy test; history of myocardial infection within 30 days; history of seizure disorder or epilepsy; concomitant or prior use of calcium channel blockers. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization] | 90 minutes post-randomization | The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Treatment duration, up to 6 hours | The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst). |
Countries
Saudi Arabia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ryanodex and Standard of Care In addition to Standard of Care measures, Ryanodex (dantrolene sodium) for injectable suspension; 250 mg/vial will be administered.
Ryanodex and Standard of Care: Ryanodex to be administered as a rapid IV push | 9 |
| Standard of Care Only (SOC) Standard of Care treatment will consist of the immediate start of cooling measures.
Standard of Care: Body cooling measures and supportive measures | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Determined to be ineligible for study | 0 | 1 |
| Overall Study | Investigator Decision | 0 | 4 |
| Overall Study | Transferred to other facility | 1 | 0 |
Baseline characteristics
| Characteristic | Standard of Care Only (SOC) | Ryanodex and Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 11.2 | 55.3 years STANDARD_DEVIATION 7.2 | 54.4 years STANDARD_DEVIATION 9 |
| BMI | 33.2 kg/m^2 STANDARD_DEVIATION 5.7 | 32.4 kg/m^2 STANDARD_DEVIATION 5.9 | 32.7 kg/m^2 STANDARD_DEVIATION 5.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 14 Participants |
| Glasgow Coma Scale Score | 5.5 units on a scale STANDARD_DEVIATION 2.7 | 5.6 units on a scale STANDARD_DEVIATION 2.7 | 5.5 units on a scale STANDARD_DEVIATION 2.6 |
| Height | 159.3 cm STANDARD_DEVIATION 7.7 | 162.8 cm STANDARD_DEVIATION 7.6 | 161.3 cm STANDARD_DEVIATION 7.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Rectal Temperature | 41.3 Degrees Celsius STANDARD_DEVIATION 0.9 | 41.8 Degrees Celsius STANDARD_DEVIATION 1.2 | 41.5 Degrees Celsius STANDARD_DEVIATION 1.1 |
| Region of Enrollment Saudi Arabia | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
| Weight | 84.2 kg STANDARD_DEVIATION 12.9 | 86.1 kg STANDARD_DEVIATION 16.9 | 85.2 kg STANDARD_DEVIATION 14.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 7 / 9 | 5 / 8 |
| serious Total, serious adverse events | 1 / 9 | 2 / 8 |
Outcome results
Primary
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization]
The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst).
Time frame: 90 minutes post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization] | 4 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13 [Time Frame: 90 Minutes Post-randomization] | 2 Participants |
Secondary
Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration]
The GCS is a validated and reliable scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst).
Time frame: Treatment duration, up to 6 hours
Population: the outcome measure data table below is a summary of results showing the cumulative proportion of subjects achieving GCS score ≥13 post-randomization at all planned time points. Data is cumulative therefore the counts in the categories below will not add up to the Number Analyzed.~score ≥ 13 post-randomization at all planned time points in the study is shown
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 at 30 min. post-randomization | 1 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 90 min. post-randomization | 4 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 60 min. post-randomization | 2 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ to 13 after 2 hr.. post-randomization | 5 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 45 min. post-randomization | 1 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 4 hr. post-randomization/follow-up phase | 5 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 75 min. post-randomization | 3 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 at end of study or early termination | 5 Participants |
| Ryanodex and Standard of Care | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 at 15 min post-randomization | 1 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 at end of study or early termination | 2 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 at 15 min post-randomization | 0 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 at 30 min. post-randomization | 0 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 45 min. post-randomization | 0 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 60 min. post-randomization | 1 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 75 min. post-randomization | 2 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 90 min. post-randomization | 2 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ to 13 after 2 hr.. post-randomization | 2 Participants |
| Standard of Care Only (SOC) | Cumulative Incidence of Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) Greater Than or Equal to 13 Over the Course of the Study [Time Frame: Study Duration] | Pts. achieving GCS score ≥ 13 after 4 hr. post-randomization/follow-up phase | 2 Participants |