Paramedic Treatment of Prolonged Seizures by Intramuscular Versus Intravenous Anticonvulsant Medications

NCT00809146 | Completed Phase 3 Results DMC

• 2 other identifiers: R01NS0530315U01NS056975-02
• Study Type: interventional
• Target: 1,023
• Locations: 1 country
• Sites: 17

Brief 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.

Conditions

Status Epilepticus

Keywords

Status Epilepticus; Emergency Medical Services; Anticonvulsants; Drug Administration Routes; Seizures

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (9)

• Number of Subjects With Endotracheal Intubation Within 30 Min After ED Arrival

  anytime before 30 minutes after ED arrival

• Number of Subjects Hospitalized

  at ED disposition on day of enrollment

• Number of Subjects Admitted to an Intensive Care Unit (ICU)

  at time of disposition on day of enrollment

• Number of Subjects With Recurrent Seizure Within 12 Hours After ED Arrival

  within 12 hours after ED arrival

• Number of Subjects With Hypotension

  participants were followed for the duration of hospital stay, an average of 6 days

Study Arms (2)

Intramuscular (IM) anticonvulsant

ACTIVE COMPARATOR

This group gets active treatment with an anticonvulsant by the intramuscular route of administration.

Drug: Intramuscular route of active treatment

Intravenous (IV) anticonvulsant

ACTIVE COMPARATOR

This group gets active treatment with an anticonvulsant by the intravenous route of administration.

Drug: Intravenous route of active treatment

Interventions

Intramuscular route of active treatment DRUG

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.

Also known as: Autoinjector

Intramuscular (IM) anticonvulsant

Intravenous route of active treatment DRUG

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.

Also known as: Ativan

Intravenous (IV) anticonvulsant

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Robert Silbergleit: lead
• Medical University of South Carolina: collaborator
• University of California, San Francisco: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (17)

University of Arizona

Tucson, Arizona, 85742, United States

Location

Stanford University

Palo Alto, California, 94304-5777, United States

Location

University of California-San Francisco

San Francisco, California, 94110, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0298, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Wayne State University

Detroit, Michigan, 48202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

New York Presbyterian Hospital

New York, New York, 10032, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

University of Pennsylvania/York

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University-Main Line

Philadelphia, Pennsylvania, 19140, United States

Location

University of Texas-Houston

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (5)

• Sherman NA, Silbergleit R, Bengelink EM, Durkalski V, Wolter KD. The Midazolam RAMPART Study Medical Records Project: A Unique Use of Real-World Data in a Complex Collaborative Partnership to Support a New Drug Application. Ther Innov Regul Sci. 2023 Jan;57(1):132-141. doi: 10.1007/s43441-022-00447-4. Epub 2022 Aug 20.

  PMID: 35987977 DERIVED

• Silbergleit R, Lowenstein D, Durkalski V, Conwit R; NETT Investigators. Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus. Epilepsia. 2013 Sep;54 Suppl 6(0 6):74-7. doi: 10.1111/epi.12284.

  PMID: 24001080 DERIVED

• Silbergleit R, Biros MH, Harney D, Dickert N, Baren J; NETT Investigators. Implementation of the exception from informed consent regulations in a large multicenter emergency clinical trials network: the RAMPART experience. Acad Emerg Med. 2012 Apr;19(4):448-54. doi: 10.1111/j.1553-2712.2012.01328.x.

  PMID: 22506949 DERIVED

• Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W; NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591-600. doi: 10.1056/NEJMoa1107494.

  PMID: 22335736 DERIVED

• Silbergleit R, Lowenstein D, Durkalski V, Conwit R; Neurological Emergency Treatment Trials (NETT) Investigators. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia. 2011 Oct;52 Suppl 8(Suppl 8):45-7. doi: 10.1111/j.1528-1167.2011.03235.x.

  PMID: 21967361 DERIVED

Related Links

• RAMPART Study Public Information Web Site

MeSH Terms

Conditions

Status Epilepticus; Seizures

Interventions

Lorazepam

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Robert Silbergleit MD, Principal Investigator
• Organization: University of Michigan

robie@umich.edu

734-232-2142

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Professor

Study Record Dates

• First Submitted: December 15, 2008
• First Posted: December 17, 2008
• Study Start: June 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: June 17, 2016
• Results First Posted: April 13, 2012

Record last verified: 2016-05

Locations

US (17)