Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intravenous Lacosamide Compared With Fosphenytoin in the Treatment of Patients With Frequent Nonconvulsive Seizures (TRENdS)

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: NCT01458522
Recruitment Status : Completed
First Posted : October 25, 2011
Results First Posted : June 11, 2018
Last Update Posted : June 11, 2018
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Aatif Husain, Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Nonconvulsive Seizures
Interventions Drug: fPHT
Drug: LCM
Enrollment 74
Recruitment Details 173 participants consented. 74 participants were randomized.
Pre-assignment Details 37 participants randomized to LCM, however 2 participants did not receive drug. 37 participants were randomized to fPHT and everyone received drug.
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description

LCM bolus of 400 mg administered over 30 minutes. If further bolus is required, 200 mg is administered. Regardless of whether the subject received a rebolus, they will begin receiving a maintenance dose 12 hrs after initial dose. Daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached end of 1st treatment arm and will crossover and receive the other drug. If any of the following did not occur the subject will be considered completed.

Subject has another seizure within 24 hrs following the 2-hr post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hrs following 2-hr post bolus observation-only period.

Subject experiences an AE that precludes further use of the 1st study drug. If crossover occurs, the subject will start over with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug. If any of the following did NOT occur the subject will be considered completed.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Period Title: Overall Study
Started 37 37
Received First Drug 35 35
Crossover to Second Drug 15 10
Completed [1] 34 26
Not Completed 3 11
Reason Not Completed
Withdrawal by Subject             2             2
Physician Decision             1             9
[1]
Completed all assigned intervention & observation. Not all subjects were assigned to crossover.
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM Total
Hide Arm/Group Description

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Total of all reporting groups
Overall Number of Baseline Participants 37 37 74
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants 37 participants 74 participants
63.8  (12.1) 63.4  (20.4) 63.6  (16.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
Female 17 21 38
Male 20 16 36
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
White 26 32 58
Black or African American 9 3 12
Asian 2 2 4
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 37 participants 37 participants 74 participants
37 37 74
1.Primary Outcome
Title Percentage of Subjects Who Experience no Nonconvulsive Seizures (NCS) for 24 Hours Following Treatment With LCM vs. fPHT, as Measured by Continuous Electroencephalography (cEEG) Monitoring.
Hide Description Percentage of subjects who experience no nonconvulsive seizures (NCS) for 24 hours (after the 2-hour observation-only period) following treatment with LCM vs. fPHT, as measured by continuous electroencephalography (cEEG) monitoring with blinded review.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Data are reported for the percentage of participants without a nonconvulsive seizure event in the period prior to crossover.
Arm/Group Title LCM 400mg fPHT 20mg PE/kg
Hide Arm/Group Description:
LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.
fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.
Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
19
  54.3%
22
  62.9%
2.Secondary Outcome
Title Percentage of Subjects Who Require a Rebolus of the Initial Antiepileptic Drugs (AED) to Control Nonconvulsive Seizures (NCS) in the LCM vs fPHT Arms.
Hide Description The percentage of subjects who require a rebolus of the initial antiepileptic drug (AED) to control nonconvulsive seizures (NCS) in the LCM vs fPHT arms.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Data are reported for the percentage of participants who require a rebolus of the initial antiepileptic drugs (AED) to control nonconvulsive seizures (NCS) in the LCM vs fPHT arms in the period prior to crossover.
Arm/Group Title LCM 400mg fPHT 20mg PE/kg
Hide Arm/Group Description:
LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.
fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.
Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
16
  45.7%
13
  37.1%
3.Secondary Outcome
Title Number of Subjects Who Required a Second Antiepileptic Drug (AED) to Control Nonconvulsive Seizures (NCS)
Hide Description Number of subjects who required a second antiepileptic drug (AED) to control nonconvulsive seizures (NCS)
Time Frame 24-26 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who crossed over to second drug
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
15
  42.9%
10
  28.6%
4.Secondary Outcome
Title Seizure Burden Change From Baseline to End of Initial Treatment
Hide Description Absolute change in seizure time (defined as the number of minutes of electrographic seizure (ESz) activity per hour) before treatment and at the end of the first treatment arm. If less than 1 hour of recording time is available, seizure time will be extrapolated to 1 hour. The maximum amount of time that can be used to determine baseline seizure time is 6 hours.
Time Frame Baseline, 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had satisfactory EEG data (sometimes EEG leads would come off)
Arm/Group Title LCM 400mg fPHT 20mg PE/kg
Hide Arm/Group Description:
LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.
fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.
Overall Number of Participants Analyzed 32 29
Mean (Standard Deviation)
Unit of Measure: min/hour
-0.58  (0.950) -0.54  (0.828)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LCM 400mg, fPHT 20mg PE/kg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.512
Comments [Not Specified]
Method Poisson regression model
Comments [Not Specified]
5.Secondary Outcome
Title Seizure Burden Change From Baseline to End of Crossover, Excluding Initial Treatment Arm
Hide Description Absolute change defined as the number of minutes of ESz activity per hour before treatment and at the end of the second treatment arm. This measure does not evaluate seizure activity in the first treatment arm. If less than 1 hour of recording time is available, seizure time will be extrapolated to 1 hour.
Time Frame baseline, 26-68 hours
Hide Outcome Measure Data
Hide Analysis Population Description
participants who had satisfactory EEG data (sometimes EEG leads would come off)
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 11 9
Mean (Standard Deviation)
Unit of Measure: min/hour
-0.78  (0.486) -0.83  (0.346)
6.Secondary Outcome
Title Time of First Bolus to End of Seizures After Initial Treatment Arm, Time From Crossover to End of Seizures in Crossover Treatment Arm
Hide Description Time of first bolus to end of seizures after initial treatment arm, time from crossover to end of seizures in crossover treatment arm
Time Frame time of first bolus to end of seizures after initial treatment arm, time from crossover to end of seizures in crossover treatment arm
Hide Outcome Measure Data
Hide Analysis Population Description
participants who had satisfactory EEG data (sometimes EEG leads would come off)
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug. If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug. If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 35 34
Mean (Standard Deviation)
Unit of Measure: hours
Initial Treatment Number Analyzed 35 participants 34 participants
8.4  (13.08) 9.8  (11.84)
Crossover Treatment Number Analyzed 14 participants 10 participants
8.2  (11.05) 1.7  (3.46)
7.Secondary Outcome
Title Number of Predefined Adverse Events (AE) After Treatment Arm 1 Administration
Hide Description Number of predefined adverse events (AE) after treatment arm 1 administration. These predefined adverse events include Patients with at least one AE of interest, Cardiac disorders, investigations, suspected hypersensitivity reactions, vascular disorders, and hypotension.
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who received treatment arm 1
Arm/Group Title LCM 400mg fPHT 20mg PE/kg
Hide Arm/Group Description:
LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.
fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.
Overall Number of Participants Analyzed 35 35
Measure Type: Number
Unit of Measure: Number of predefined AEs
4 5
8.Secondary Outcome
Title Percentage of Subjects in Whom Study Drug is Withdrawn Early After Treatment With Treatment Arm 1
Hide Description Percentage of subjects in whom study drug is withdrawn early after treatment with treatment arm 1
Time Frame baseline to end of treatment arm 1
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title LCM Treatment fPHT Treatment
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 35 35
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.7%
3
   8.6%
9.Secondary Outcome
Title Days in the Intensive Care Unit/Hospital
Hide Description Data was acquired in a manner consistent with determining if one treatment arm (LCM first, then fPHT versus fPHT first, then LCM) resulted in more days of hospitalization than the other over the course of the study.
Time Frame initial bolus to end of study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 37 37
Mean (Standard Deviation)
Unit of Measure: days
Days in ICU 7.4  (8.36) 6.5  (8.73)
Days in hospital 12.7  (7.63) 12.5  (10.03)
10.Secondary Outcome
Title Change in Functional Status as Measured by the Functional Disability Scale at Day 7 to 9 Postrandomization and Day 30 Post-randomization in the LCM vs fPHT Arms.
Hide Description Change in functional status as measured by the Functional Disability Scale, using a 0-29 rating (0=w/o disability; 29=extreme vegetative state) at Day 7 to 9 postrandomization and Day 30 post-randomization in the LCM first, then fPHT versus fPHT first, then LCM arms. Data was analyzed in a manner consistent with determining if one treatment arm resulted in a greater change in functional status than the other.
Time Frame Baseline to day 7-9, baseline to day 30
Hide Outcome Measure Data
Hide Analysis Population Description
participants who completed the Functional Disability Scale
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 20 28
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from baseline to day 7-9 Number Analyzed 20 participants 28 participants
-4.1  (7.64) 0.3  (4.52)
Change from baseline to day 30 Number Analyzed 14 participants 20 participants
-8.5  (11.73) -3.7  (5.01)
11.Secondary Outcome
Title Percentage of All Subjects Who Have Had a Seizure, Are on Antiepileptic Drug (AED) Therapy, and Are Alive/Dead at Day 30
Hide Description Percentage of all subjects who have had a seizure, are on antiepileptic drug (AED) therapy, and are alive and dead at day 30. Data was acquired in a manner consistent with determining if one treatment arm (LCM first, then fPHT versus fPHT first, then LCM) resulted in a greater effect on seizures, antiepileptic drug (AED) use, and survival at day 30 after the acute treatment period. The acute treatment period could range from 6 to 30 hours.
Time Frame both acute treatment periods to 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title LCM First, Then fPHT fPHT First, Then LCM
Hide Arm/Group Description:

LCM treatment arm, a bolus of 400 mg will be administered over 30 minutes. If a further bolus is required, 200 mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400 mg or 600 mg) divided into 2 doses.

If after initial treatment and any of the following occurs, subject will have reached the end of the first treatment arm and will “cross over” and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period.

fPHT treatment arm, a bolus of 20 mg PE/kg will be administered at a rate of no greater than 75 mg PE/minute. If a further bolus is required, 5 mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5 mg PE/kg divided into 2 doses.

If after initial treatment and any of the following occurs, the subject will have reached the end of the first treatment arm and will "cross over" and begin receiving the other drug.

Subject has another seizure within 24 hours following the 2-hour post-rebolus observation-only period.

Subject dose not receive a rebolus but has a seizure within 24 hours following 2-hour post bolus observation-only period.

Subject experiences an AE that precludes further use of the first study drug.

If crossover occurs, the subject will "start over" with the second drug, going through the same observation-only period, rebolusing (if necessary).

Overall Number of Participants Analyzed 45 50
Measure Type: Number
Unit of Measure: percentage of participants
any seizure within 30 days after acute tx period 27.4 38.9
AED use within 30 days after acute tx period 82.2 74.0
Died within 30 days after randomization 15.5 16.0
Time Frame Adverse event data was collected for 30 days after last dose of study drug (approximately 30-32 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Participants Receiving LCM 400mg All Participants Receiving fPHT 20mg PE/kg
Hide Arm/Group Description Participants who receive a bolus of 400mg administered over 30 minutes. If a further bolus is required, 200mg will be administered. Regardless of whether the subject received a rebolus, he or she will begin receiving a maintenance dose 12 hours after the initial dose. The daily maintenance dose will be the same as the total bolus (400mg or 600mg) divided into 2 doses. Participants who receive a bolus of 20mg PE/kg administered at a rate no greater than 75mg PE/minute. If a further bolus is required, 5mg PE/kg will be administered. The daily maintenance dose for fPHT will be 5mg PE/kg divided into 2 doses.
All-Cause Mortality
All Participants Receiving LCM 400mg All Participants Receiving fPHT 20mg PE/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   7/45 (15.56%)   8/50 (16.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
All Participants Receiving LCM 400mg All Participants Receiving fPHT 20mg PE/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   10/45 (22.22%)   13/50 (26.00%) 
Cardiac disorders     
Bradycardia   1/45 (2.22%)  0/50 (0.00%) 
Atrial tachycardia   0/45 (0.00%)  1/50 (2.00%) 
Infections and infestations     
Herpes simplex encephalitis   0/45 (0.00%)  1/50 (2.00%) 
Sepsis   0/45 (0.00%)  1/50 (2.00%) 
Septic shock   0/45 (0.00%)  1/50 (2.00%) 
Encephalitis viral   0/45 (0.00%)  1/50 (2.00%) 
Injury, poisoning and procedural complications     
Subdural haematoma   2/45 (4.44%)  1/50 (2.00%) 
Toxicity to various agents   0/45 (0.00%)  2/50 (4.00%) 
Nervous system disorders     
Cerebral hemorrhage   2/45 (4.44%)  1/50 (2.00%) 
Neurological decompensation   1/45 (2.22%)  0/50 (0.00%) 
Grand mal convulsion   0/45 (0.00%)  1/50 (2.00%) 
Haemorrhage intracranial   0/45 (0.00%)  1/50 (2.00%) 
Haemorrhagic stroke   0/45 (0.00%)  1/50 (2.00%) 
Intracranial pressure increased   0/45 (0.00%)  1/50 (2.00%) 
Renal and urinary disorders     
Renal failure   0/45 (0.00%)  1/50 (2.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure   2/45 (4.44%)  1/50 (2.00%) 
respiratory failure   1/45 (2.22%)  0/50 (0.00%) 
Vascular disorders     
Hypotension   2/45 (4.44%)  2/50 (4.00%) 
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 0%
All Participants Receiving LCM 400mg All Participants Receiving fPHT 20mg PE/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   22/45 (48.89%)   27/50 (54.00%) 
Blood and lymphatic system disorders     
Thrombocytopenia   0/45 (0.00%)  1/50 (2.00%) 
Cardiac disorders     
Bradycardia   2/45 (4.44%)  2/50 (4.00%) 
Atrial tachycardia   0/45 (0.00%)  1/50 (2.00%) 
Gastrointestinal disorders     
Dysphagia   1/45 (2.22%)  0/50 (0.00%) 
Vomiting   0/45 (0.00%)  2/50 (4.00%) 
Dysphagia   0/45 (0.00%)  1/50 (2.00%) 
General disorders     
Infusion site extravasation   0/45 (0.00%)  1/50 (2.00%) 
Pyrexia   1/45 (2.22%)  0/50 (0.00%) 
Immune system disorders     
Hypersensitivity   0/45 (0.00%)  1/50 (2.00%) 
Infections and infestations     
Urinary tract infection   1/45 (2.22%)  0/50 (0.00%) 
Herpes simplex encephalitis   0/45 (0.00%)  1/50 (2.00%) 
Sepsis   0/45 (0.00%)  1/50 (2.00%) 
Septic shock   0/45 (0.00%)  1/50 (2.00%) 
Encephalitis viral   0/45 (0.00%)  1/50 (2.00%) 
Pneumonia   0/45 (0.00%)  1/50 (2.00%) 
Injury, poisoning and procedural complications     
Subdural haematoma   2/45 (4.44%)  1/50 (2.00%) 
Incorrect route of drug administration   0/45 (0.00%)  1/50 (2.00%) 
Toxicity to various agents   0/45 (0.00%)  2/50 (4.00%) 
Investigations     
Alanine aminotransferase increased   1/45 (2.22%)  0/50 (0.00%) 
Aspartate aminotransferase increased   1/45 (2.22%)  0/50 (0.00%) 
Heart rate abnormal   1/45 (2.22%)  0/50 (0.00%) 
Weight decreased   1/45 (2.22%)  0/50 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage   2/45 (4.44%)  1/50 (2.00%) 
Neurological decompensation   1/45 (2.22%)  0/50 (0.00%) 
Grand mal convulsion   0/45 (0.00%)  1/50 (2.00%) 
Haemorrhage intracranial   0/45 (0.00%)  1/50 (2.00%) 
Haemorrhagic stroke   0/45 (0.00%)  1/50 (2.00%) 
Intracranial pressure increased   0/45 (0.00%)  1/50 (2.00%) 
Renal and urinary disorders     
Renal failure   0/45 (0.00%)  1/50 (2.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure   2/45 (4.44%)  1/50 (2.00%) 
Epistaxis   1/45 (2.22%)  0/50 (0.00%) 
Respiratory failure   3/45 (6.67%)  0/50 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash pruritic   1/45 (2.22%)  1/50 (2.00%) 
rash   0/45 (0.00%)  2/50 (4.00%) 
Vascular disorders     
hypotension   2/45 (4.44%)  4/50 (8.00%) 
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Name/Title: Aatif M. Husain, M.D.
Organization: Duke University
Phone: 919-668-8700
Responsible Party: Aatif Husain, Duke University
ClinicalTrials.gov Identifier: NCT01458522     History of Changes
Other Study ID Numbers: Pro00033295
Pro00037794 ( Other Identifier: Duke Site Protocol Number )
DCRI-CEMC101.01
First Submitted: October 20, 2011
First Posted: October 25, 2011
Results First Submitted: June 1, 2017
Results First Posted: June 11, 2018
Last Update Posted: June 11, 2018