Paramedic Treatment of Prolonged Seizures by Intramuscular Versus Intravenous Anticonvulsant Medications

Status Epilepticus Clinical Trial

— RAMPART  

Official title:

A Double-blind Randomized Clinical Trial of the Efficacy of IM Midazolam Versus IV Lorazepam in the Pre-hospital Treatment of Status Epilepticus by Paramedics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00809146
• Other study ID #: R01NS053031
• Secondary ID: 5U01NS056975-02
• Status: Completed
• Phase: Phase 3
• First received: December 15, 2008
• Last updated: April 13, 2012
• Start date: June 2009
• Est. completion date: January 2011

Study information

• Verified date: April 2012
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The goal of this non-inferiority trial is to determine which type of routine care is the best for paramedics to stop someone from seizing.

Description:

Seizures are a common medical problem. Although they can be frightening to watch, most seizures are brief and stop by themselves. Seizures that don't stop in seconds or minutes are a dangerous life-threatening medical emergency. Paramedics often have medications that can stop seizures, but the best way to give the medicines is not known. Paramedics often give medicine directly into a vein, which is called intravenous (IV) administration. This works well, but can be hard to do in a person who is seizing. It can also take some time and delay treatment. Another way to give the medicine is as a shot given into a muscle, which is called intramuscular (IM) administration. Giving the medicine this way is faster, but it may not stop the seizure as quickly.

This clinical trial, the Rapid Anti-convulsant Medication Prior to ARrival Trial (RAMPART), is designed to figure out whether giving anti-seizure medicine works similarly well and more quickly when given through an IV or when given as a shot in the muscle. Two similar medicines will be used. Both are already used by paramedics in the field and by doctors in the hospital to stop seizures. One is commonly given by IV, and the other is commonly given as a shot in the muscle. In this study, the shot will be given using a device similar to an EpiPen—which is an autoinjector used by people with severe allergies.

Approximately 1,024 persons whose seizures are continuing after emergency medical service (EMS) arrival and who meet all eligibility criteria will be enrolled in the trial. Every participant will be treated with anti-seizure medicine by the paramedics. At random, half the participants will be in one group and half in another. Half the participants will receive the study medicine through an IV and will be given a shot in the muscle without medicine (placebo). The other half will receive the medicine as a shot in the muscle plus an IV without medicine (placebo).

In September 2010, more rapid than expected enrollment made it feasible to increase the sample size of the study from 800 to 1,024 with the already available funding. The goals of the expansion were to enroll more pediatric subjects (since the trial was enrolling slightly fewer than anticipated) and to improve the power of the study to 90%, which was initially desired. It is important to understand that the extended enrollment was not a sample size re-estimation in any way. The opportunity to extend the trial is pragmatic, based solely on the early enrollment success of the trial. It is not informed by the planned interim analyses that have been performed, the results of which remain sequestered, and there have been no unscheduled interim analyses. The firewall that prevents the blinded leadership from any knowledge of the outcome data has been diligently maintained throughout the process of proposing and implementing this extension.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1023
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Paramedics or reliable witnesses verify 5 minutes of either continuous seizure activity or of repeated convulsive seizure activity where the patient does not regain consciousness (operationally defined as meaningful speech or obeying commands) between seizures.

• Patient is still seizing at the time of paramedic treatment with study medications.

• Estimated weight equal to or greater than 13 kg.

• Subject to be transported to a RAMPART participating hospital.

Exclusion Criteria:

• Major trauma as the precipitant of the seizure

• Hypoglycemia (as defined by local EMS protocol or a glucose < 60 mg/dL)

• Known allergy to midazolam or lorazepam

• Cardiac arrest or heart rate (HR) <40 beats per minute

• Sensitivity to benzodiazepines

• Medical alert tag marked with "RAMPART declined"

• Prior treatment of this seizure with diazepam autoinjector as part of another study

• Known pregnancy

• Prisoners

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Status Epilepticus

Intervention

Drug:
• Intramuscular route of active treatment
IM administration by autoinjector of midazolam 5 mg for subjects under estimated weight of 40 kg or midazolam 10 mg for subjects with estimated weight of 40 kg or above, IV administration of matching volume of IV flush.
• Intravenous route of active treatment
IV administration of lorazepam 2 mg for subjects under estimated weight of 40 kg or midazolam 4 mg for subjects with estimated weight of 40 kg or above, IM administration by autoinjector of matching volume of saline.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Wayne State University	Detroit	Michigan
United States	University of Texas-Houston	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	New York Presbyterian Hospital	New York	New York
United States	Stanford University	Palo Alto	California
United States	Temple University-Main Line	Philadelphia	Pennsylvania
United States	University of Pennsylvania/York	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California-San Francisco	San Francisco	California
United States	University of Arizona	Tucson	Arizona

Sponsors (4)

Lead Sponsor	Collaborator
Robert Silbergleit	Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS), University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Termination of Seizures at ED Arrival With no Rescue Therapy Given	The primary outcome was termination of seizures before arrival in the emergency department (ED) without the need for the paramedics to provide rescue therapy. Subjects did not reach the primary outcome if they were having seizures on arrival in the emergency department or if they received rescue medication before arrival. Termination of seizures on arrival was determined according to the clinical judgment of the attending emergency physician and was based on examination of the subjects, their clinical course, and results of any routine diagnostic testing.	Duration of prehospital care, outcome is determined upon arrival at the ED on the day of enrollment (average 20 minutes).	No
Secondary	Number of Subjects With Endotracheal Intubation Within 30 Min After ED Arrival	Endotracheal intubation performed or attempted by EMS or within 30 minutes after ED arrival is abstracted from the ED record physician and nursing records. Endotracheal intubation includes placement of a definitive tracheal airway (oro-, naso-, cricothyroidotomy, or tracheostomy) for support of respirations or protection of airway. Non-definitive and/or non-tracheal airways (oral or nasal airways, laryngeal mask airways, or esophageal obturator airways) are not included if the patient is not subsequently intubated unless specifically deemed to have been used in lieu of tracheal intubation.	anytime before 30 minutes after ED arrival	Yes
Secondary	Number of Subjects Hospitalized	Hospital and ICU admission from the ED, and length of stay, is abstracted from the hospital admission record. ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient.	at ED disposition on day of enrollment	Yes
Secondary	Number of Subjects Admitted to an Intensive Care Unit (ICU)	Hospital and ICU admission from the ED, and length of stay, is abstracted from the hospital admission record. ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient.	at time of disposition on day of enrollment	Yes
Secondary	Number of Subjects With Recurrent Seizure Within 12 Hours After ED Arrival	Acute seizure recurrence is defined as any further convulsive or electrographic seizures occurring in the first 12 hours of hospitalization, if they require additional antiepileptic medications, in subjects that had been determined not to be having seizures on ED arrival.	within 12 hours after ED arrival	Yes
Secondary	Number of Subjects With Hypotension	Acute hypotension is defined as a systolic blood pressure of < 90 mmHg sustained for greater than 5 minutes and for which the patient was treated with a continuous IV infusion of a vasopressor.	during hospitalization	Yes
Secondary	Number of Subjects With IM Injection-site Complications	IM injection site complications are defined as any symptoms or signs of injury or reaction at the site of the study IM injection requiring treatment. This includes extensive hematoma requiring treatment (decompression, pressure dressings, or discontinuation of anticoagulant or antithrombotic medications). Treatment does not include imaging without other interventions. This definition also includes wound infection requiring antibiotic therapy, retained foreign bodies requiring exploration and removal, or other similar wound problems.	during hospitalization	Yes
Secondary	Number of Subjects With IV Injection-site Complications	IV insertion site complications are defined as any symptoms or signs of injury or reaction at the site of the study IV placed by paramedics and used for study medication. This includes thrombosis, phlebitis, or skin infection requiring specific treatment including compresses, antibiotics, or wound care.	during hospitalization	Yes
Secondary	Length of Intensive Care Unit (ICU) Stay in Days	Continuous days of initial ICU stay from time of admission	during hospitalization	No
Secondary	Length of Hospital Stay in Days	Continuous acute care inpatient hospital days from day of admission until discharge	during hospitalization	No

External Links

•   RAMPART Study Public Information Web Site