Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

Brief Summary:
This is a randomized, double-blind, placebo-controlled trial, designed to evaluate the efficacy and safety of SAGE-547 administered as a continuous intravenous infusion to subjects in Super-Refractory Status Epilepticus (SRSE).

Condition or disease Intervention/treatment Phase
Super-Refractory Status Epilepticus Drug: SAGE-547 Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SAGE-547 Injection in the Treatment of Subjects With Super-Refractory Status Epilepticus
Study Start Date : June 2015
Actual Primary Completion Date : July 18, 2017
Actual Study Completion Date : August 11, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: SAGE-547
Intravenous
Drug: SAGE-547
Placebo Comparator: Placebo
Intravenous
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. 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 [ Time Frame: 7 days ]
    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.


Secondary Outcome Measures :
  1. Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression [ Time Frame: Up to 21 days ]
    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.

  2. Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion [ Time Frame: Day 6 ]
    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.

  3. Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression [ Time Frame: Up to 21 days ]
    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.

  4. Change in Clinical Global Impression Scale (CGI) [ Time Frame: Up to 21 days ]
    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.

  5. Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12 [ Time Frame: Up to 21 days ]
    Here, study visits followed by "R" indicate the Open-label Treatment Period.

  6. Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12 [ Time Frame: Up to 21 days ]
    Here, study visits followed by "R" indicate the Open-label Treatment Period.

  7. Number of Separate Episodes of Status Epilepticus Up to Visit 12 [ Time Frame: Up to 21 days ]
    Here, study visits followed by "R" indicate the Open-label Treatment Period.

  8. Number of Participants With a New Diagnosis of Epilepsy After Visit 11 [ Time Frame: Up to 21 days ]
    Here, study visits followed by "R" indicate the Open-label Treatment Period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects two (2) years of age and older
  • Subjects who have:

    • Failed to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial anti-epileptic drug [AED] treatment), according to institution standard of care, and;
    • Failed to respond to at least one second-line agent (e.g., phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam or other urgent control AED), according to institution standard of care, and;
    • Not previously been administered a third-line agent but have been admitted to an intensive care unit with the intent of administering at least one third-line agent for at least 24 hours; or who have previously failed zero, one or more wean attempts from third-line agents and are now on continuous intravenous infusions of one or more third-line agent and in an EEG burst or seizure suppression pattern; or who have previously failed one or more wean attempts from third-line agents and are now either not on a continuous intravenous infusion of at least one third-line agent or are on a continuous intravenous infusion of one or more third-line agent but not in an EEG burst or seizure suppression pattern

Exclusion Criteria:

  • Subjects with SRSE due to anoxic/hypoxic encephalopathy with highly malignant/ malignant EEG features
  • Children (subjects aged less than 17 years) with an encephalopathy due to a rapidly progressing underlying neurological disorder
  • Subjects who have any of the following:

    1. a glomerular filtration rate (GFR) low enough to warrant dialysis but for whatever reason, dialysis is not planned or non-continuous dialysis planned (that would not adequately remove Captisol®);
    2. severe cardiogenic or vasodilatory shock requiring two or more pressors that is not related to third-line agent use;
    3. fulminant hepatic failure;
    4. no reasonable expectation of recovery (for instance, a likely outcome is persistent vegetative state) or life-expectancy, in the experience of the investigator, is less than 30 days.
  • Subjects who are being administered more than three third-line agents concomitantly or in whom the qualifying wean cannot be completed per protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02477618


  Show 173 Study Locations
Sponsors and Collaborators
Sage Therapeutics
Investigators
Layout table for investigator information
Principal Investigator: Eric Rosenthal, MD Massachusetts General Hospital
Principal Investigator: Mark Wainwright, MD, PhD Ann & Robert H Lurie Children's Hospital of Chicago
  Study Documents (Full-Text)

Documents provided by Sage Therapeutics:
Statistical Analysis Plan  [PDF] August 31, 2017
Study Protocol  [PDF] May 3, 2017


Additional Information:
Layout table for additonal information
Responsible Party: Sage Therapeutics
ClinicalTrials.gov Identifier: NCT02477618     History of Changes
Other Study ID Numbers: 547-SSE-301
First Posted: June 23, 2015    Key Record Dates
Results First Posted: May 2, 2019
Last Update Posted: May 2, 2019
Last Verified: April 2019

Additional relevant MeSH terms:
Layout table for MeSH terms
Status Epilepticus
Seizures
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Pregnanolone
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs