Paramedic Treatment of Prolonged Seizures by Intramuscular Versus Intravenous Anticonvulsant Medications (RAMPART)

This study has been completed.
Sponsor:
Collaborators:
Medical University of South Carolina
University of California, San Francisco
Information provided by (Responsible Party):
Robert Silbergleit, University of Michigan
ClinicalTrials.gov Identifier:
NCT00809146
First received: December 15, 2008
Last updated: April 13, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Status Epilepticus
Drug: Intramuscular route of active treatment
Drug: Intravenous route of active treatment
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Number of Subjects With Termination of Seizures at ED Arrival With no Rescue Therapy Given [ Time Frame: Duration of prehospital care, outcome is determined upon arrival at the ED on the day of enrollment (average 20 minutes). ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Subjects With Endotracheal Intubation Within 30 Min After ED Arrival [ Time Frame: anytime before 30 minutes after ED arrival ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects Hospitalized [ Time Frame: at ED disposition on day of enrollment ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects Admitted to an Intensive Care Unit (ICU) [ Time Frame: at time of disposition on day of enrollment ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects With Recurrent Seizure Within 12 Hours After ED Arrival [ Time Frame: within 12 hours after ED arrival ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects With Hypotension [ Time Frame: during hospitalization ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects With IM Injection-site Complications [ Time Frame: during hospitalization ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects With IV Injection-site Complications [ Time Frame: during hospitalization ] [ Designated as safety issue: Yes ]
    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.

  • Length of Intensive Care Unit (ICU) Stay in Days [ Time Frame: during hospitalization ] [ Designated as safety issue: No ]
    Continuous days of initial ICU stay from time of admission

  • Length of Hospital Stay in Days [ Time Frame: during hospitalization ] [ Designated as safety issue: No ]
    Continuous acute care inpatient hospital days from day of admission until discharge


Enrollment: 1023
Study Start Date: June 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intramuscular (IM) anticonvulsant
This group gets active treatment with an anticonvulsant by the intramuscular route of administration.
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.
Other Name: Autoinjector
Active Comparator: Intravenous (IV) anticonvulsant
This group gets active treatment with an anticonvulsant by the intravenous route of administration.
Drug: 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.
Other Name: Ativan

Detailed 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809146

Locations
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85742
United States, California
Stanford University
Palo Alto, California, United States, 94304-5777
University of California-San Francisco
San Francisco, California, United States, 94110
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536-0298
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55414
United States, New York
New York Presbyterian Hospital
New York, New York, United States, 10032
United States, Ohio
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
University of Pennsylvania/York
Philadelphia, Pennsylvania, United States, 19104
Temple University-Main Line
Philadelphia, Pennsylvania, United States, 19140
United States, Texas
University of Texas-Houston
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Robert Silbergleit
Medical University of South Carolina
University of California, San Francisco
Investigators
Principal Investigator: Robert Silbergleit, MD University of Michigan
Principal Investigator: Daniel H Lowenstein, MD University of California, San Francisco
Principal Investigator: Valerie L Durkalski, PhD Medical University of South Carolina
  More Information

Additional Information:
No publications provided by University of Michigan

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert Silbergleit, Principal Investigator, Associate Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT00809146     History of Changes
Other Study ID Numbers: R01NS053031, 5U01NS056975-02
Study First Received: December 15, 2008
Results First Received: March 18, 2012
Last Updated: April 13, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
Status Epilepticus
Emergency Medical Services
Anticonvulsants
Drug Administration Routes
Seizures

Additional relevant MeSH terms:
Status Epilepticus
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014