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A Study With SAGE-547 for Super-Refractory Status Epilepticus

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ClinicalTrials.gov Identifier: NCT02477618
Recruitment Status : Completed
First Posted : June 23, 2015
Results First Posted : May 2, 2019
Last Update Posted : May 2, 2019
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Super-Refractory Status Epilepticus
Interventions Drug: SAGE-547
Drug: Placebo
Enrollment 132
Recruitment Details Participants took part in the study at 122 investigative sites in Canada, United States, Austria, Denmark, Estonia, Finland, France, Germany, Israel, Italy, Serbia, Spain and United Kingdom from 31 July 2015 to 11 August 2017.
Pre-assignment Details Participants 2 years of age and older with Super-Refractory Status Epilepticus were eligible. One participant in the placebo group was erroneously given SAGE-547 and was, therefore, included in the SAGE- 547 group.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment. SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Period Title: Overall Study
Started 65 67
Intent-to-Treat Analysis Set 66 66
Completed [1] 50 53
Not Completed 15 14
Reason Not Completed
Completed Visits but Discontinued Drug             2             1
Died in Double-Blind Treatment Period             11             11
Adverse Event             1             1
Transferred Away from Study Site             1             0
Left Study Site for Rehabilitation             0             1
[1]
Participants who completed both study drug and study visits.
Arm/Group Title Placebo SAGE-547 Total
Hide Arm/Group Description Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment. SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration. Total of all reporting groups
Overall Number of Baseline Participants 65 67 132
Hide Baseline Analysis Population Description
The Safety Analysis Set included all participants who had an infusion of blinded study drug initiated. One participant in the placebo group was erroneously given SAGE-547 and was, therefore, included in the SAGE-547 group.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 67 participants 132 participants
37.8  (22.69) 41.3  (23.89) 39.6  (23.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 67 participants 132 participants
Female
30
  46.2%
35
  52.2%
65
  49.2%
Male
35
  53.8%
32
  47.8%
67
  50.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 67 participants 132 participants
White
47
  72.3%
45
  67.2%
92
  69.7%
Black
14
  21.5%
13
  19.4%
27
  20.5%
Asian
3
   4.6%
5
   7.5%
8
   6.1%
Other
1
   1.5%
4
   6.0%
5
   3.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 67 participants 132 participants
Hispanic or Latino
10
  15.4%
6
   9.0%
16
  12.1%
Not Hispanic or Latino
55
  84.6%
61
  91.0%
116
  87.9%
1.Primary Outcome
Title Number of Participants Able to be Weaned Off All Third-Line Agents Prior to End of Double-Blind SAGE-547 or Placebo Infusion, and Remain Off All Third-Line Agents for ≥ 24 Hours Following the End of SAGE-547 or Placebo Infusion
Hide Description Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression electroencephalogram (EEG) pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG. A responder was a participant who was able to be weaned off all third-line agents prior to the end of the SAGE-547 or placebo infusion and remain off all third-line agents for >=24 hours after the end of the study drug infusion. The primary analysis was a comparison between SAGE-547 and placebo of the proportion of responders.
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Measure Type: Count of Participants
Unit of Measure: Participants
28
  42.4%
29
  43.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.878
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.056
Confidence Interval (2-Sided) 95%
0.527 to 2.118
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression
Hide Description Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG. A responder was a participant who was able to be weaned off all third-line agents prior to the end of the SAGE-547 or placebo infusion and remain off all third-line agents for >=24 hours after the end of the study drug infusion. The primary analysis was a comparison between SAGE-547 and placebo of the proportion of responders.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, overall number of participants analyzed (N) indicates participants analyzed for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 28 29
Median (Full Range)
Unit of Measure: days
13.500
(0.06 to 18.00)
14.000
(0.18 to 16.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.636
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.747
Confidence Interval (2-Sided) 95%
0.222 to 2.507
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion
Hide Description Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG.
Time Frame Day 6
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Measure Type: Count of Participants
Unit of Measure: Participants
45
  68.2%
38
  57.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.623
Confidence Interval (2-Sided) 95%
0.303 to 1.282
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression
Hide Description Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, overall number of participants analyzed (N) indicates participants analyzed for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 45 38
Median (Full Range)
Unit of Measure: days
7.000
(0.00 to 20.00)
15.000
(0.00 to 19.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.328
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.683
Confidence Interval (2-Sided) 95%
0.318 to 1.466
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Clinical Global Impression Scale (CGI)
Hide Description The CGI scale was used to integrate several sources of information into a single rating of a participant’s condition. The CGI was rated on a 7-point scale, from a minimum of 0 to a maximum of 7, where 0 = Not assessed; 1 = Normal, not at all ill; 2 = Borderline physically ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill participants. A negative change from baseline indicates improvement. A positive change from baseline indicates worsening. Here, study visits followed by “R” indicate the Open-label Treatment Period.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, number of participants analyzed (N) indicates participants with available data at each time point for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Mean (Standard Deviation)
Unit of Measure: units on scale
Baseline Number Analyzed 66 participants 65 participants
6.0  (0.89) 5.9  (1.31)
Visit 12 Number Analyzed 33 participants 32 participants
-1.0  (1.42) -0.6  (1.91)
Visit 12R Number Analyzed 18 participants 20 participants
-0.7  (1.36) -0.5  (1.19)
6.Secondary Outcome
Title Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12
Hide Description Here, study visits followed by “R” indicate the Open-label Treatment Period.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, number of participants analyzed (N) indicates participants with available data at each time point for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Mean (Standard Deviation)
Unit of Measure: days
Visit 12 Number Analyzed 41 participants 40 participants
10.05  (6.738) 11.15  (6.058)
Visit 12R Number Analyzed 25 participants 26 participants
11.08  (6.557) 9.23  (6.345)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.339
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.583
Confidence Interval (2-Sided) 95%
0.193 to 1.763
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12
Hide Description Here, study visits followed by “R” indicate the Open-label Treatment Period.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, number of participants analyzed (N) indicates participants with available data at each time point for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Mean (Standard Deviation)
Unit of Measure: days
Visit 12 Number Analyzed 41 participants 40 participants
8.22  (7.289) 7.50  (6.626)
Visit 12R Number Analyzed 25 participants 26 participants
7.52  (7.054) 6.08  (5.932)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.817
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.086
Confidence Interval (2-Sided) 95%
0.539 to 2.189
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Separate Episodes of Status Epilepticus Up to Visit 12
Hide Description Here, study visits followed by “R” indicate the Open-label Treatment Period.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, number of participants analyzed (N) indicates participants with available data at each time point for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Mean (Standard Deviation)
Unit of Measure: episodes
Visit 12 Number Analyzed 9 participants 5 participants
1.3  (0.50) 1.4  (0.55)
Visit 12R Number Analyzed 5 participants 8 participants
2.2  (2.17) 1.0  (0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, SAGE-547
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.567
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.9 to 0.5
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With a New Diagnosis of Epilepsy After Visit 11
Hide Description Here, study visits followed by “R” indicate the Open-label Treatment Period.
Time Frame Up to 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-Treat Analysis Set included all participants who had an infusion of blinded study drug initiated. Here, number of participants analyzed (N) indicates participants with available data at each time point for this outcome measure.
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description:
Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment.
SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
Overall Number of Participants Analyzed 66 66
Measure Type: Count of Participants
Unit of Measure: Participants
Visit 12 Number Analyzed 34 participants 34 participants
0
   0.0%
5
  14.7%
Visit 12R Number Analyzed 20 participants 23 participants
5
  25.0%
3
  13.0%
Time Frame Up to approximately 27 days
Adverse Event Reporting Description The Safety Analysis Set included all subjects who had an infusion of blinded study drug initiated.
 
Arm/Group Title Placebo SAGE-547
Hide Arm/Group Description Placebo was administered over the course of 6 days, beginning with a 1-hour dose rate equivalent to 300 micrograms per kilogram per hour (μg/kg/h) of the active arm loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment), which included a step-wise taper during the last 24 hours of treatment. SAGE-547 Injection was administered over the course of 6 days, beginning with a 1-hour 300 μg/kg/h loading dose, followed by a maintenance period achieving a maximum of 90 μg/kg/h (double-blind treatment) or 150 μg/kg/h (open-label treatment), both of which included a step-wise taper during the last 24 hours of treatment. Eligible participants, who did not respond to blinded study treatment, were allowed to enter an Open-label Treatment Period of identical duration.
All-Cause Mortality
Placebo SAGE-547
Affected / at Risk (%) Affected / at Risk (%)
Total   12/65 (18.46%)   17/67 (25.37%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo SAGE-547
Affected / at Risk (%) Affected / at Risk (%)
Total   22/65 (33.85%)   27/67 (40.30%) 
Cardiac disorders     
Cardiac arrest  1  4/65 (6.15%)  5/67 (7.46%) 
Cardio-respiratory arrest  1  1/65 (1.54%)  1/67 (1.49%) 
Pulseless electrical activity  1  1/65 (1.54%)  1/67 (1.49%) 
Atrial flutter  1  0/65 (0.00%)  1/67 (1.49%) 
Bradycardia  1  0/65 (0.00%)  1/67 (1.49%) 
Bundle branch block  1  0/65 (0.00%)  1/67 (1.49%) 
Torsade de pointes  1  0/65 (0.00%)  1/67 (1.49%) 
Ventricular fibrillation  1  0/65 (0.00%)  1/67 (1.49%) 
Nodal rhythm  1  1/65 (1.54%)  0/67 (0.00%) 
Ventricular tachycardia  1  1/65 (1.54%)  0/67 (0.00%) 
Congenital, familial and genetic disorders     
Mitochondrial DNA mutation  1  0/65 (0.00%)  1/67 (1.49%) 
Endocrine disorders     
Diabetes insipidus  1  2/65 (3.08%)  0/67 (0.00%) 
Eye disorders     
Mydriasis  1  1/65 (1.54%)  0/67 (0.00%) 
Pupil fixed  1  1/65 (1.54%)  0/67 (0.00%) 
Gastrointestinal disorders     
Intestinal ischaemia  1  1/65 (1.54%)  1/67 (1.49%) 
Abdominal compartment syndrome  1  0/65 (0.00%)  1/67 (1.49%) 
Ileus  1  0/65 (0.00%)  1/67 (1.49%) 
Melaena  1  0/65 (0.00%)  1/67 (1.49%) 
Rectal haemorrhage  1  0/65 (0.00%)  1/67 (1.49%) 
Intra-abdominal haemorrhage  1  1/65 (1.54%)  0/67 (0.00%) 
General disorders     
Hypothermia  1  0/65 (0.00%)  1/67 (1.49%) 
Device related thrombosis  1  1/65 (1.54%)  0/67 (0.00%) 
Hyperthermia  1  1/65 (1.54%)  0/67 (0.00%) 
Multiple organ dysfunction syndrome  1  1/65 (1.54%)  0/67 (0.00%) 
Hepatobiliary disorders     
Cholestasis  1  0/65 (0.00%)  1/67 (1.49%) 
Cirrhosis alcoholic  1  1/65 (1.54%)  0/67 (0.00%) 
Hepatic failure  1  1/65 (1.54%)  0/67 (0.00%) 
Hepatic function abnormal  1  1/65 (1.54%)  0/67 (0.00%) 
Infections and infestations     
Septic shock  1  2/65 (3.08%)  3/67 (4.48%) 
Pneumonia  1  3/65 (4.62%)  1/67 (1.49%) 
Sepsis  1  2/65 (3.08%)  1/67 (1.49%) 
Pneumonia staphylococcal  1  0/65 (0.00%)  1/67 (1.49%) 
Serratia sepsis  1  1/65 (1.54%)  0/67 (0.00%) 
Subdural empyema  1  1/65 (1.54%)  0/67 (0.00%) 
Urosepsis  1  1/65 (1.54%)  0/67 (0.00%) 
Injury, poisoning and procedural complications     
Subdural haematoma  1  1/65 (1.54%)  2/67 (2.99%) 
Brain herniation  1  3/65 (4.62%)  1/67 (1.49%) 
Nerve injury  1  0/65 (0.00%)  1/67 (1.49%) 
Investigations     
Transaminases increased  1  1/65 (1.54%)  1/67 (1.49%) 
Electrocardiogram QT prolonged  1  0/65 (0.00%)  1/67 (1.49%) 
Hepatic enzyme increased  1  0/65 (0.00%)  1/67 (1.49%) 
Nuclear magnetic resonance imaging brain abnormal  1  0/65 (0.00%)  1/67 (1.49%) 
Liver function test abnormal  1  1/65 (1.54%)  0/67 (0.00%) 
Metabolism and nutrition disorders     
Metabolic acidosis  1  1/65 (1.54%)  1/67 (1.49%) 
Hyperkalaemia  1  0/65 (0.00%)  1/67 (1.49%) 
Propofol infusion syndrome  1  1/65 (1.54%)  0/67 (0.00%) 
Nervous system disorders     
Brain oedema  1  1/65 (1.54%)  2/67 (2.99%) 
Status epilepticus  1  2/65 (3.08%)  1/67 (1.49%) 
Cerebral atrophy  1  0/65 (0.00%)  1/67 (1.49%) 
Cerebral infarction  1  0/65 (0.00%)  1/67 (1.49%) 
Posterior reversible encephalopathy syndrome  1  0/65 (0.00%)  1/67 (1.49%) 
Cerebral ischaemia  1  1/65 (1.54%)  0/67 (0.00%) 
Haemorrhage intracranial  1  1/65 (1.54%)  0/67 (0.00%) 
Product Issues     
Device dislocation  1  0/65 (0.00%)  1/67 (1.49%) 
Psychiatric disorders     
Delirium  1  1/65 (1.54%)  0/67 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  0/65 (0.00%)  1/67 (1.49%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/65 (1.54%)  2/67 (2.99%) 
Acute respiratory failure  1  0/65 (0.00%)  1/67 (1.49%) 
Hypoxia  1  0/65 (0.00%)  1/67 (1.49%) 
Obstructive airways disorder  1  0/65 (0.00%)  1/67 (1.49%) 
Pleural effusion  1  0/65 (0.00%)  1/67 (1.49%) 
Pneumothorax  1  0/65 (0.00%)  1/67 (1.49%) 
Acute respiratory distress syndrome  1  1/65 (1.54%)  0/67 (0.00%) 
Pulmonary oedema  1  1/65 (1.54%)  0/67 (0.00%) 
Respiratory arrest  1  1/65 (1.54%)  0/67 (0.00%) 
Skin and subcutaneous tissue disorders     
Drug reaction with eosinophilia and systemic symptoms  1  0/65 (0.00%)  1/67 (1.49%) 
Angioedema  1  1/65 (1.54%)  0/67 (0.00%) 
Surgical and medical procedures     
Withdrawal of life support  1  7/65 (10.77%)  11/67 (16.42%) 
Vascular disorders     
Hypotension  1  1/65 (1.54%)  2/67 (2.99%) 
Neurogenic shock  1  1/65 (1.54%)  0/67 (0.00%) 
1
Term from vocabulary, MedDRA v19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo SAGE-547
Affected / at Risk (%) Affected / at Risk (%)
Total   58/65 (89.23%)   60/67 (89.55%) 
Blood and lymphatic system disorders     
Anaemia  1  7/65 (10.77%)  12/67 (17.91%) 
Leukocytosis  1  3/65 (4.62%)  4/67 (5.97%) 
Thrombocytopenia  1  7/65 (10.77%)  3/67 (4.48%) 
Cardiac disorders     
Tachycardia  1  4/65 (6.15%)  8/67 (11.94%) 
Atrial fibrillation  1  2/65 (3.08%)  5/67 (7.46%) 
Sinus tachycardia  1  0/65 (0.00%)  4/67 (5.97%) 
Gastrointestinal disorders     
Diarrhoea  1  7/65 (10.77%)  12/67 (17.91%) 
Constipation  1  8/65 (12.31%)  10/67 (14.93%) 
Vomiting  1  2/65 (3.08%)  5/67 (7.46%) 
Abdominal distension  1  0/65 (0.00%)  4/67 (5.97%) 
General disorders     
Pyrexia  1  21/65 (32.31%)  19/67 (28.36%) 
Hyperthermia  1  1/65 (1.54%)  5/67 (7.46%) 
Peripheral swelling  1  0/65 (0.00%)  4/67 (5.97%) 
Oedema  1  4/65 (6.15%)  3/67 (4.48%) 
Hypothermia  1  4/65 (6.15%)  1/67 (1.49%) 
Infections and infestations     
Urinary tract infection  1  14/65 (21.54%)  13/67 (19.40%) 
Pneumonia  1  11/65 (16.92%)  13/67 (19.40%) 
Fungal infection  1  1/65 (1.54%)  4/67 (5.97%) 
Sepsis  1  4/65 (6.15%)  3/67 (4.48%) 
Investigations     
Aspartate aminotransferase increased  1  6/65 (9.23%)  5/67 (7.46%) 
Lipase increased  1  6/65 (9.23%)  5/67 (7.46%) 
Alanine aminotransferase increased  1  5/65 (7.69%)  4/67 (5.97%) 
Blood potassium decreased  1  1/65 (1.54%)  4/67 (5.97%) 
White blood cell count increased  1  0/65 (0.00%)  4/67 (5.97%) 
Electrocardiogram QT prolonged  1  4/65 (6.15%)  3/67 (4.48%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  11/65 (16.92%)  10/67 (14.93%) 
Hypophosphataemia  1  6/65 (9.23%)  8/67 (11.94%) 
Metabolic acidosis  1  2/65 (3.08%)  8/67 (11.94%) 
Hypernatraemia  1  6/65 (9.23%)  6/67 (8.96%) 
Hyponatraemia  1  4/65 (6.15%)  5/67 (7.46%) 
Hyperglycaemia  1  1/65 (1.54%)  5/67 (7.46%) 
Hyperammonaemia  1  0/65 (0.00%)  5/67 (7.46%) 
Fluid overload  1  2/65 (3.08%)  4/67 (5.97%) 
Hypocalcaemia  1  7/65 (10.77%)  3/67 (4.48%) 
Psychiatric disorders     
Agitation  1  4/65 (6.15%)  5/67 (7.46%) 
Renal and urinary disorders     
Haematuria  1  1/65 (1.54%)  4/67 (5.97%) 
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  8/65 (12.31%)  14/67 (20.90%) 
Atelectasis  1  4/65 (6.15%)  5/67 (7.46%) 
Pulmonary oedema  1  4/65 (6.15%)  3/67 (4.48%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  8/65 (12.31%)  5/67 (7.46%) 
Erythema  1  2/65 (3.08%)  4/67 (5.97%) 
Rash  1  2/65 (3.08%)  4/67 (5.97%) 
Vascular disorders     
Hypertension  1  6/65 (9.23%)  8/67 (11.94%) 
Hypotension  1  10/65 (15.38%)  6/67 (8.96%) 
Deep vein thrombosis  1  4/65 (6.15%)  3/67 (4.48%) 
1
Term from vocabulary, MedDRA v19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Results Point of Contact
Name/Title: Helen Colquhoun, MD - Vice President, Medical Science
Organization: Sage Therapeutics
Phone: (617) 229-5234
Responsible Party: Sage Therapeutics
ClinicalTrials.gov Identifier: NCT02477618     History of Changes
Other Study ID Numbers: 547-SSE-301
First Submitted: June 2, 2015
First Posted: June 23, 2015
Results First Submitted: April 11, 2019
Results First Posted: May 2, 2019
Last Update Posted: May 2, 2019