Trial Outcomes & Findings for Efficacy and Safety of Ryanodex® (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS) (NCT NCT02513095)
NCT ID: NCT02513095
Last Updated: 2021-06-29
Results Overview
Number of subjects achieving a Glasgow Coma Scale(GCS) ≥ 13 at or prior to 90 minutes post-randomization. The Glasgow Coma Scale (GCS) is a reliable and objective way of recording the initial and subsequent level of consciousness in a person after a brain injury. The range of total GCS score is 3 to15 where a higher GCS score represents a better outcome. The scores of subscales are summed to determine the total score\*. A GCS score of 13-15 is considered Mild impairment of consciousness; a GCS score of 9-12 is considered Moderate impairment of consciousness; and a GCS score of 3-8 is considered Severe. \*Subscales: Eyes Response -Spontaneous=4; To sound =3; To Pressure=2; None=1; not tested. Verbal Response- Oriented=5; Confused=4; Words=3; Sounds=2; None-1; Not tested. Motor Response: Obeys Commands=6; Localizes=5; Normal Flexion=4; Abnormal Flexion=3; Extension=2; None=1; Not tested.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
90 minutes post-randomization
Results posted on
2021-06-29
Participant Flow
Due to the life-threatening nature of EHS, eligible subjects were immediately randomized to enter the study Treatment Phase (up to 120 minutes duration)
Participant milestones
| Measure |
Active
Ryanodex plus Standard of Care
|
Control
Standard of Care Only
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
|
Overall Study
Treatment Phase - Up to 120 Minutes
|
17
|
17
|
|
Overall Study
COMPLETED
|
17
|
17
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of Ryanodex® (EGL-4104) as Adjuvant Treatment in Subjects With Exertional Heat Stroke (EHS)
Baseline characteristics by cohort
| Measure |
Ryanodex Plus Standard of Care
n=17 Participants
Ryanodex (dantrolene sodium) for injectable suspension administered as an IV bolus, in addition to standard of care (SOC) treatment.
Dantrolene sodium for injectable suspension: Ryanodex will be administered as a rapid IV push as a single doses of 2 mg/kg or as 1 mg/kg.
|
Standard of Care Only (SOC)
n=17 Participants
Standard of Care (SOC) treatment only, consisting of body cooling and supportive measures implemented immediately.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Glasgow Coma Scale
|
6.1 units on a scale
STANDARD_DEVIATION 3.98 • n=5 Participants
|
5.9 units on a scale
STANDARD_DEVIATION 3.18 • n=7 Participants
|
6.0 units on a scale
STANDARD_DEVIATION 3.55 • n=5 Participants
|
PRIMARY outcome
Timeframe: 90 minutes post-randomizationNumber of subjects achieving a Glasgow Coma Scale(GCS) ≥ 13 at or prior to 90 minutes post-randomization. The Glasgow Coma Scale (GCS) is a reliable and objective way of recording the initial and subsequent level of consciousness in a person after a brain injury. The range of total GCS score is 3 to15 where a higher GCS score represents a better outcome. The scores of subscales are summed to determine the total score\*. A GCS score of 13-15 is considered Mild impairment of consciousness; a GCS score of 9-12 is considered Moderate impairment of consciousness; and a GCS score of 3-8 is considered Severe. \*Subscales: Eyes Response -Spontaneous=4; To sound =3; To Pressure=2; None=1; not tested. Verbal Response- Oriented=5; Confused=4; Words=3; Sounds=2; None-1; Not tested. Motor Response: Obeys Commands=6; Localizes=5; Normal Flexion=4; Abnormal Flexion=3; Extension=2; None=1; Not tested.
Outcome measures
| Measure |
Ryanodex Plus Standard of Care
n=17 Participants
Ryanodex plus Standard of Care. Ryanodex will be administered as a rapid IV push as a single doses of 2 mg/kg or as 1 mg/kg.
|
Standard of Care
n=17 Participants
Standard of Care Only
|
|---|---|---|
|
Number of Subjects Achieving Recovery of Level of Consciousness Defined as a Glasgow Coma Scale (GCS) GCS ≥ 13
|
5 Participants
|
2 Participants
|
Adverse Events
Ryanodex
Serious events: 4 serious events
Other events: 17 other events
Deaths: 1 deaths
Standard of Care Only (SOC)
Serious events: 3 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ryanodex
n=17 participants at risk
Ryanodex (dantrolene sodium) for injectable suspension administered as an IV bolus, in addition to standard of care (SOC) treatment.
Dantrolene sodium for injectable suspension: Ryanodex will be administered as a rapid IV push as a single doses of 2 mg/kg or as 1 mg/kg.
|
Standard of Care Only (SOC)
n=17 participants at risk
Standard of Care (SOC) treatment only, consisting of body cooling and supportive measures implemented immediately.
|
|---|---|---|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Cardiac disorders
Cardiac Arrest
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Cardiac disorders
Cardio-Respiratory Arrest
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Metabolism and nutrition disorders
Diabetic Ketoacidosis
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
11.8%
2/17 • Number of events 2 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
Other adverse events
| Measure |
Ryanodex
n=17 participants at risk
Ryanodex (dantrolene sodium) for injectable suspension administered as an IV bolus, in addition to standard of care (SOC) treatment.
Dantrolene sodium for injectable suspension: Ryanodex will be administered as a rapid IV push as a single doses of 2 mg/kg or as 1 mg/kg.
|
Standard of Care Only (SOC)
n=17 participants at risk
Standard of Care (SOC) treatment only, consisting of body cooling and supportive measures implemented immediately.
|
|---|---|---|
|
Gastrointestinal disorders
Dysphagia
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Gastrointestinal disorders
Nausea
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
General disorders
Chills
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
17.6%
3/17 • Number of events 3 • .Up to 30 days post-discharge.
|
|
Investigations
Alanine Aminotransferase Increased
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Investigations
Aspartate Aminotransferase Increased
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
11.8%
2/17 • Number of events 2 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Investigations
Hepatic Enzyme Increased
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Investigations
Oxygen Saturation Decreased
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Investigations
Platelet Count Decreased
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
11.8%
2/17 • Number of events 2 • .Up to 30 days post-discharge.
|
|
Investigations
White Blood Cell Count Increased
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Investigations
Dehydration
|
11.8%
2/17 • Number of events 2 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Investigations
Hypoglycemia
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Nervous system disorders
Amnesia
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Nervous system disorders
Somnolence
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Psychiatric disorders
Agitation
|
11.8%
2/17 • Number of events 2 • .Up to 30 days post-discharge.
|
17.6%
3/17 • Number of events 3 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma Exacerbation
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
11.8%
2/17 • Number of events 2 • .Up to 30 days post-discharge.
|
35.3%
6/17 • Number of events 6 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
0.00%
0/17 • .Up to 30 days post-discharge.
|
|
Vascular disorders
Hypotension
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
5.9%
1/17 • Number of events 1 • .Up to 30 days post-discharge.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI has no right to discuss/publish/disclose the trial data.
- Publication restrictions are in place
Restriction type: OTHER