Treatment of Refractory Status Epilepticus

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00265616
• Collaborator: (none)
• Enrollment: 23
• Locations: 5
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether propofol or barbiturates should be preferred in the treatment of status epilepticus (continuous seizure activity) refractory to 2 standard antiepileptic agents.

Condition or Disease	Intervention/Treatment	Phase
Status Epilepticus	Drug: propofol; Drug: thiopental/pentobarbital	Phase 3

Detailed Description

Refractory status epilepticus (SE) develops in 31%-44% of patients with SE, with a mortality of 16%-23%. Coma induction is advocated for its management. Propofol and barbiturates are the most used agents, but no comparative study has been performed. In consideration of the uncertainty regarding the relative effectiveness, despite several retrospective data, a prospective investigation is needed.

The objective is to assess the effectiveness (SE control, adverse events) of a first course of propofol versus barbiturates in the treatment of refractory SE, in adults with refractory SE not due to cerebral anoxia.

Comparison: Coma induction with standardized doses of propofol or barbiturates titrated towards burst-suppression on EEG, then assessment of the proportion of patients achieving a control of SE.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Clinical Trial for the Treatment of Refractory Status Epilepticus
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 propofol, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined	Drug: propofol; liquid, mg/kg.h, titrated after EEG; Other Names: Disoprivan
Active Comparator: 2 thiopental/pentobarbital, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined	Drug: thiopental/pentobarbital; liquid, mg/kg.h, titrated after EEG; Other Names: Pentotal /Thiopentone

Outcome Measures

Primary Outcome Measures

1. Refractory Status Epilepticus Controlled With First Course of Study Drug [after return of continuous EEG activity (typically after 36 hours - 5 days)]

   Control of status epilepticus refractory to benzodiazepines and a first antiepileptic drug after administration of the study drug; dichotomous assessment (yes/no)

Secondary Outcome Measures

1. Clinical Outcome at Day 21 [21 days]

   Return to baseline clinical conditions (i.e.: no new handicap, no death)

2. Patients With Infectious Complications Requiring Specific Treatment [10 days]

3. Patients With Hypotension Requiring Specific Treatment [10 days]

4. Patients With Propofol Infusion Syndrome [10 days]

   Propofol infusion syndrome (PRIS) is a severe metabolic alteration with elevation of lactate, CK, and triglycerides.

5. Intubation Time in Survivors [Up to 3 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with refractory status epilepticus not due to cerebral anoxia, needing coma induction for clinical management.

Exclusion Criteria:

• Age < 16 years old.

• Known pregnancy.

• Cerebral anoxia as SE etiology.

• Epilepsia partialis continua (simple partial SE).

• Known intolerance to the study drugs.

• Known mitochondrial disorder, hyperlipidemia, or significant rhabdomyolysis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Inselspital	Bern	BE	Switzerland
4	CHUV	Lausanne	VD	Switzerland
5	Hôpitaux Universitaires de Genève	Geneva		Switzerland

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Andrea O. Rossetti, MD, BrighamHospital/CHUV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Andrea O. Rossetti, MD, Dr, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00265616
• Other Study ID Numbers: RSE study, protocol#62/06
• First Posted: Dec 15, 2005
• Last Update Posted: Apr 9, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Andrea O. Rossetti, MD, Dr, Brigham and Women's Hospital: Refractory status epilepticus,; coma-induction,; treatment,; propofol,; barbiturates,; efficacy,; safety.
• Additional relevant MeSH terms: Status Epilepticus; Pentobarbital; Thiopental; Propofol

Study Results

Participant Flow

Recruitment Details	Rcruitment in participating centers took part between 2006 and 2010.

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG);no maximum doses defined.	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG); no maximum doses defined.
Period Title: Overall Study
STARTED	14	9
COMPLETED	14	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Propofol	Thiopental/Pentobarbital	Total
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	Total of all reporting groups
Overall Participants	14	9	23
Age (Count of Participants)
<=18 years	0 0%	1 11.1%	1 4.3%
Between 18 and 65 years	9 64.3%	4 44.4%	13 56.5%
>=65 years	5 35.7%	4 44.4%	9 39.1%
Sex: Female, Male (Count of Participants)
Female	7 50%	6 66.7%	13 56.5%
Male	7 50%	3 33.3%	10 43.5%
Region of Enrollment (participants) [Number]
United States	5 35.7%	2 22.2%	7 30.4%
Switzerland	9 64.3%	7 77.8%	16 69.6%

Outcome Measures

1. Secondary Outcome

Title	Clinical Outcome at Day 21
Description	Return to baseline clinical conditions (i.e.: no new handicap, no death)
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
Measure Participants	14	9
Number [participants]	5 35.7%	3 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Thiopental/Pentobarbital
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Patients With Infectious Complications Requiring Specific Treatment
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
Measure Participants	14	9
Number [participants]	7 50%	6 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Thiopental/Pentobarbital
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Patients With Hypotension Requiring Specific Treatment
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
Measure Participants	14	9
Number [participants]	7 50%	5 55.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Thiopental/Pentobarbital
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Patients With Propofol Infusion Syndrome
Description	Propofol infusion syndrome (PRIS) is a severe metabolic alteration with elevation of lactate, CK, and triglycerides.
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
Measure Participants	14	9
Number [participants]	1 7.1%	0 0%

5. Primary Outcome

Title	Refractory Status Epilepticus Controlled With First Course of Study Drug
Description	Control of status epilepticus refractory to benzodiazepines and a first antiepileptic drug after administration of the study drug; dichotomous assessment (yes/no)
Time Frame	after return of continuous EEG activity (typically after 36 hours - 5 days)

Outcome Measure Data

Analysis Population Description

Number of patients fulfilling primary outcome criteria

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
Measure Participants	14	9
Number [participants]	6 42.9%	2 22.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Thiopental/Pentobarbital
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Intubation Time in Survivors
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propofol	Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
Measure Participants	14	9
Median (Full Range) [days]	4	13.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Thiopental/Pentobarbital
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Propofol		Thiopental/Pentobarbital
Arm/Group Description	titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)		titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG)
All Cause Mortality
	Propofol		Thiopental/Pentobarbital
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Propofol		Thiopental/Pentobarbital
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		1/9 (11.1%)
Cardiac disorders
propofol infusion syndrome (non fatal)	1/14 (7.1%)	1	0/9 (0%)	0
Gastrointestinal disorders
paralytic ileus (fatal)	0/14 (0%)	0	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Propofol		Thiopental/Pentobarbital
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.