Paramedic Treatment of Prolonged Seizures by Intramuscular Versus Intravenous Anticonvulsant Medications

NCT ID: NCT00809146

Last Updated: 2016-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1023 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-01-31

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.

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.

Conditions

Status Epilepticus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intramuscular (IM) anticonvulsant

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

Group Type: ACTIVE_COMPARATOR

Intramuscular route of active treatment

Intervention Type: 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.

Intravenous (IV) anticonvulsant

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

Group Type: ACTIVE_COMPARATOR

Intravenous route of active treatment

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Autoinjector; Ativan

Eligibility 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Robert Silbergleit

OTHER

Sponsor Role: lead

Responsible Party

Robert Silbergleit

Principal Investigator, Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert Silbergleit, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Daniel H Lowenstein, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Valerie L Durkalski, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

University of Arizona

Tucson, Arizona, United States

Stanford University

Palo Alto, California, United States

University of California-San Francisco

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

University of Kentucky

Lexington, Kentucky, United States

University of Maryland

Baltimore, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

Wayne State University

Detroit, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

New York Presbyterian Hospital

New York, New York, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania/York

Philadelphia, Pennsylvania, United States

Temple University-Main Line

Philadelphia, Pennsylvania, United States

University of Texas-Houston

Houston, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35987977 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24001080 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22506949 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22335736 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21967361 (View on PubMed)

Related Links

http://rampart.umich.edu

RAMPART Study Public Information Web Site

Other Identifiers

5U01NS056975-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01NS053031

Identifier Type: -

Identifier Source: org_study_id