A Phase 3 interventional study of Intramuscular route of active treatment and Intravenous route of active treatment in Status Epilepticus, sponsored by Robert Silbergleit. Completed at 17 sites in United States. Per ClinicalTrials.gov, last updated 2016-06-17.
Sponsored by Robert Silbergleit · Phase 3, Interventional, and Treatment
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.
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.
126 studies on the registry are indexed under Status Epilepticus; 37 are open to participants now.
This study's enrollment of 1,023 is above the median of 70 across 74 interventional studies indexed under Status Epilepticus.
Browse Status Epilepticus studies →Robert Silbergleit is the lead sponsor of 2 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
This group gets active treatment with an anticonvulsant by the intramuscular route of administration.
Drug: Intramuscular route of active treatment
This group gets active treatment with an anticonvulsant by the intravenous route of administration.
Drug: Intravenous 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.
Also known as: Autoinjector
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
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.
Time frame: Duration of prehospital care, outcome is determined upon arrival at the ED on the day of enrollment (average 20 minutes).
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.
Time frame: anytime before 30 minutes after ED arrival
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.
Time frame: at ED disposition on day of enrollment
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.
Time frame: at time of disposition on day of enrollment
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.
Time frame: within 12 hours after ED arrival
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.
Time frame: participants were followed for the duration of hospital stay, an average of 6 days
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.
Time frame: participants were followed for the duration of hospital stay, an average of 6 days
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.
Time frame: participants were followed for the duration of hospital stay, an average of 6 days
Length of Intensive Care Unit (ICU) Stay in Days
Continuous days of initial ICU stay from time of admission
Time frame: participants were followed for the duration of hospital stay, an average of 6 days
Length of Hospital Stay in Days
Continuous acute care inpatient hospital days from day of admission until discharge
Time frame: participants were followed for the duration of hospital stay, an average of 6 days
Subjects treated for status epilepticus in the prehospital setting by paramedics were enrolled at the scene between June 2009 and January 2011. A total of 1023 subject enrollments represented 893 unique subjects with a reenrollment rate of 13%. RAMPART involved 4314 paramedics, 33 EMS agencies, and 79 receiving hospitals across the United States.
| Milestone | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant |
|---|---|---|
| Started | 448 | 445 |
| Completed | 448 | 445 |
| Not completed | 0 | 0 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects With Termination of Seizures at ED Arrival With no Rescue Therapy Given | 329 | 282 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects With Endotracheal Intubation Within 30 Min After ED Arrival | 63 | 64 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects Hospitalized | 258 | 292 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects Admitted to an Intensive Care Unit (ICU) | 128 | 161 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects With Recurrent Seizure Within 12 Hours After ED Arrival | 51 | 47 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects With Hypotension | 12 | 13 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects With IM Injection-site Complications | 4 | 2 |
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.
| participants | IM Midazolam | IV Lorazepam |
|---|---|---|
| Number of Subjects With IV Injection-site Complications | 0 | 3 |
Continuous days of initial ICU stay from time of admission
| days | IM Midazolam | IV Lorazepam |
|---|---|---|
| Length of Intensive Care Unit (ICU) Stay in Days | 5.7 ± 9.5 | 4.1 ± 4.7 |
Continuous acute care inpatient hospital days from day of admission until discharge
| days | IM Midazolam | IV Lorazepam |
|---|---|---|
| Length of Hospital Stay in Days | 6.7 ± 10.0 | 5.5 ± 6.4 |
Collected over Serious adverse events were collected through subject end of study (emergency department or hospital discharge).. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| IM Midazolam | — | 137/514 (26.7%) | 103/514 (20%) |
| IV Lorazepam | — | 156/509 (30.6%) | 95/509 (18.7%) |
| Event | IM Midazolam | IV Lorazepam |
|---|---|---|
| Respiratory depressionRespiratory, thoracic and mediastinal disorders | 33/514 | 51/509 |
| Depressed level of consciousnessNervous system disorders | 49/514 | 45/509 |
| ConvulsionNervous system disorders | 33/514 | 39/509 |
| Pneumonia/ Aspiration pneumoniaInfections and infestations | 2/514 | 11/509 |
| Mental status changesNervous system disorders | 9/514 | 10/509 |
| Sepsis/SIRS/organ failureInfections and infestations | 8/514 | 8/509 |
| Myocardial infarctionCardiac disorders | 5/514 | 7/509 |
| HypotensionCardiac disorders | 5/514 | 7/509 |
| RhabdomyolysisMusculoskeletal and connective tissue disorders | 5/514 | 5/509 |
| Alcohol/Drug withdrawal syndromeGeneral disorders | 5/514 | 5/509 |
| Event | IM Midazolam | IV Lorazepam |
|---|---|---|
| ConvulsionNervous system disorders | 45/514 | 38/509 |
| Vomiting/NauseaGastrointestinal disorders | 15/514 | 23/509 |
| PyrexiaGeneral disorders | 23/514 | 14/509 |
| Mental status changesNervous system disorders | 20/514 | 20/509 |
| Age, Continuous(years) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| Mean | 43 ± 22 | 44 ± 22 | 43 ± 22 |
| Age, Customized(participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| 0-5 years | 32 | 29 | 61 |
| 6-10 years | 15 | 20 | 35 |
| 11-20 years | 28 | 21 | 49 |
| 21-40 years | 114 | 112 | 226 |
| 41-60 years | 169 | 169 | 338 |
| >61 years | 90 | 94 | 184 |
| Sex: Female, Male(Participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| Female | 198 | 207 | 405 |
| Male | 250 | 238 | 488 |
| Ethnicity (NIH/OMB)(Participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| Hispanic or Latino | 49 | 57 | 106 |
| Not Hispanic or Latino | 310 | 290 | 600 |
| Unknown or Not Reported | 89 | 98 | 187 |
| Race (NIH/OMB)(Participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| American Indian or Alaska Native | 3 | 5 | 8 |
| Asian | 8 | 14 | 22 |
| Native Hawaiian or Other Pacific Islander | 2 | 1 | 3 |
| Black or African American | 229 | 224 | 453 |
| White | 165 | 183 | 348 |
| More than one race | 9 | 5 | 14 |
| Unknown or Not Reported | 32 | 13 | 45 |
| Region of Enrollment(participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| United States | 448 | 445 | 893 |
| Dose tier(participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| children with an estimated weight of 13 to 40 kg | 62 | 59 | 121 |
| Children estimated >40kg and All Adults | 386 | 386 | 772 |
| History of epilepsy(participants) | Intramuscular (IM) Anticonvulsant | Intravenous (IV) Anticonvulsant | Total |
|---|---|---|---|
| Yes | 293 | 295 | 588 |
| No | 111 | 103 | 214 |
| Not documented | 44 | 47 | 91 |
1 further baseline measures are reported on the registry.
This study is completed, as verified in May 2016. You cannot join it, but the record below documents what was studied.
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Robert Silbergleit