Clinical Trials

Current Trials

ACCESS - Early versus Standard to Cardiac Catheterization Lab Activation in Resuscitated Cardiac Arrest Survivors with Non-ST Segment Elevation MI

Public Notification of an Exception to the Requirements for Informed Consent under Emergency Circumstances for a Cardiac Arrest Research Study

This announcement serves as public notification of a Cardiac Arrest research study that will begin January 2018 and will be performed in Minneapolis and St Paul Minnesota (and several other US locations) using the DHHS research regulations allowing exception to informed consent in emergency research circumstances.  The study will include all adult victims of ventricular fibrillation out-of-hospital cardiac arrest (an irregular heart rhythm that does not pump blood) who are transported to participating Twin Cites hospitals.  All patients will receive standard resuscitation care.  The only difference for this study will be that half of the patients will be randomized (a 50 - 50 chance, similar to “flipping a coin”) to go directly to the cardiac catheterization lab (CCL) and the other half will be transported directly to the Intensive Care Unit (ICU).

Cardiac arrest is the sudden loss of pulse and breathing. Cardiopulmonary resuscitation (CPR) is typically performed until normal heart function can be restored. The purpose of this research study is to determine if more of these patients do better if initially transported to the CCL or initially transported to the ICU for consultation by a cardiologist. Patients who are known to have a clot in their heart arteries are taken to the “cardiac cath lab” in order to have an invasive procedure (called “catheterization”) to remove the clot and restore blood flow to their heart. Patients are known to have a clot if there are certain signs on their electrocardiogram (ECG). However, previous research has shown that patients that have an out-of-hospital cardiac arrest due to ventricular fibrillation (an irregular heart rhythm that does not pump blood) may be likely to have a clot in their heart arteries but not have signs of a clot on their ECG.

All research contains risks.  Risks common to both treatments are infection, damage to the liver, damage to the heart with low blood pressure, damage to multiple organs in the body, seizures, repeated cardiac arrest, survival to hospital discharge with decreased function, and death. Risks associated with catheterization are heart attack (caused by the catheterization), stroke (caused by the catheterization), injury to the catheterized artery, tear in the heart or heart artery, fluid or blood around the heart, bleeding requiring blood transfusion, kidney damage (caused by contrast dye), and death (as a direct complication of catheterization). The risks of these complications generally occur less than 1 out of 100 times. Patients who are initially transported to the CCL have an increased risk of having catheterization performed without having an actual clot in their heart arteries. Patients who are initially transported to the ICU have an increased risk of delayed catheterization to remove a potential clot in their heart arteries.

The information that is obtained from this study may be useful scientifically and possibly helpful to others.  The benefit that may reasonably be expected from participating in this study is improved treatments for out-of-hospital ventricular fibrillation cardiac arrest or an increased chance of survival, but these potential benefits are not guaranteed.  There are no financial risks or benefits for study participation.  For this study, both treatment arms are standards of care. The study team will make every effort to protect your personal health information and keep it confidential, but it is possible that an unauthorized person might see it.  The scientific or medical information not identifiable with a patient resulting from the study will be presented at meetings and published so that the information can be useful to others. 

The DHHS has implemented regulations allowing an exception to informed consent under emergency research circumstances where acquiring written informed consent is impossible and there is reasonable scientific evidence to suggest a possible benefit from a new intervention. These regulations require public notification to inform the community that a research project will be done that may impact members of the local population.  This notification must be made prior to the initiation of the study, which will begin January 2018, and continue through 2021.  Public notification will also occur after the study is completed.

This study meets the regulatory federal guidelines for exception to informed consent under emergency circumstances because informed consent cannot be obtained from a victim of sudden cardiac arrest.  Interested parties with questions or concerns or those who do not wish to participate in this trial and would like to request an opt-out bracelet, are encouraged to contact the principal investigator, Demetris Yannopoulos, MD, or visit the WEB site at https://www.dom.umn.edu/divisions/cardiovascular/division-sections/resuscitation-clinical-research/access.   Feedback from the community may be used to further modify the design of the study.

Minnesota Participating Hospitals:

  • University of Minnesota Medical Center Fairview
  • Southdale Hospital
  • Hennepin County Medical Center
  • Regions Hospital
  • Methodist Hospital  
  • St Joes Hospital

HOBIT - Hyperbaric Oxygen Brain Injury Treatment Trial

There continues to be an overarching problem of high mortality and poor outcome for victims of severe traumatic brain injury (TBI). Preclinical and clinical investigations indicate that hyperbaric oxygen (HBO2) has a positive impact on reducing brain injury and improving outcomes in severe TBI. By markedly increasing oxygen (O2) delivery to the traumatized brain, HBO2 can reverse the lack of O2 that precipitates cellular energy failure and subsequent brain cell death. In past clinical investigations, HBO2 in comparison to standard care has significantly improved energy production in the brain and improved clinical outcome. However, prior to a formal phase III definitive efficacy study, important information is required regarding optimizing the HBO2 treatment schedule to be instituted in terms of pressure and frequency and other parameters. The lungs in severe TBI patients have frequently been compromised by direct lung injury and/or acquired ventilator pneumonia and are susceptible to O2 toxicity. It is essential to determine the most effective HBO2 dose schedule without producing O2 toxicity and clinical complications.

Hyperbaric Oxygen Brain Injury Treatment Trial (HOBIT) is a proposed adaptive clinical trial designed to answer these questions and to provide important data to plan a definitive phase III efficacy trial. Primary aims of this trial are to select, patients with severe TBI, the combination of HBO2 treatment parameters that is most likely to demonstrate improvement in the outcome of severe TBI patients in a subsequent phase III trial. Also, the trial will determine, patients with severe TBI, whether there is a > 50% probability of HBO2 treatment demonstrating improvement in the outcome of severe TBI in a subsequent confirmatory phase III trial. This trial will enroll 200 subjects over 3 1/2 years. This trial is supported and sponsored by the SIREN-NETT Network which is funded by the National Institutes of Neurologic Disease and Stroke to conduct clinical trials such as the one described. 

Minnesota SIREN Hub Participating Hospitals:

  • Hennepin County Medical Center
  • University of Iowa Hospital and Clinics
  • University of Nebraska Medical Center

CLOVERS - Crystalloid Liberal or Fluid Restrictive Resuscitation in Sepsis

The CLOVERS trial is a phase 3, randomized, nonblinded, multicenter study to determine the impact of a restrictive fluids strategy (vasopressors first followed by rescue fluids) as compared to a liberal fluid strategy (fluids first followed by rescue vasopressors) on 90-day in-hospital mortality in patients with sepsis-induced hypotension.

BOOST-3- Brain Oxygen Optimization in Severe Traumatic Brain Injury-3 Trial

Traumatic brain injury (TBI) is a major cause of death and disability in developed societies. Every year, approximately 3.5 million Americans sustain a TBI, of which 50,000 die, and another 300,000 are hospitalized and survive the injury. This proposed study focuses on the most severely injured of this group, approximately 27,000 Americans each year who experience prolonged coma from a TBI, and require sophisticated care in neurological Intensive Care Units. This group experiences high rates of mortality and morbidity, and only 20% make a good recovery resulting in an enormous psychosocial burden on patients, their families, and society. This study proposes to determine whether a treatment protocol based on brain tissue oxygen monitoring, using technology that has been available for over 10 years, improves neurologic outcome in this most severely injured group of patients. BOOST-3 will enroll 1094 subjects.

 

A study of emergency care involving victims of severe brain trauma is to be performed in this area.

Regions Hospital (St. Paul, MN), in affiliation with the University of Minnesota, is conducting a research study to learn if either of two strategies for monitoring and treating patients with severe traumatic brain injury in the intensive care unit (ICU) is more likely to help them get better.  Because head injury is a life threatening condition requiring immediate treatment, some patients will be enrolled without consent if a family member or representative is not rapidly available. Before the study starts, we will consult with the community. We welcome your feedback and questions.  For more information or to decline participation in this study, please visit boost3trial.org or contact our study staff at 651-254-3744.

Primary Investigator: Dr. Michael Brogan, MD 

Study Coordinator: Jenny Koops

Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) Network

The Department of Emergency Medicine has received a National Institute of Health (NIH) grant for the successor of NETT, the SIREN clinical research network. This grant is to sustain and grow a network to improve the emergency care of patients within the emergency department or within emergency medical services (prehospital) by executing large multicenter clinical trials.

Learn More


Completed Trials

Neurological Emergencies Treatment Trials (NETT) Network

The Department of Emergency Medicine has received a National Institutes of Health (NIH) grant for a second five-year cycle of the project called Neurological Emergencies Treatment Trials (NETT) Network.  The grant is to sustain and grow a network to improve the emergency care of patients with neurological emergencies by executing clinical trials.  NETT will transition to SIREN in late 2017.

SHINE - Stroke Hyperglycemia Insulin Network Effort

This is a multicenter, prospective, randomized, controlled trial, with blinded outcomes. It aims to determine the efficacy and provide further safety data on the use of insulin infusion therapy for glucose control in hyperglycemic acute ischemic stroke patients. Treatment with insulin infusion will be given within 12 hours of symptom onset. The primary outcome to be assessed at 90 days will be the difference in favorable outcome measured by the Modified Rankin Scale score in the insulin infusion group compared to the control group. The rates of symptomatic hypoglycemia with prolonged neurological worsening as well as asymptomatic hypoglycemia will be assessed. The secondary outcomes will assess additional neurological and functional outcomes. This highly collaborative research program is nearly guaranteed to advance the field of stroke care.

The SHINE trial was closed to enrollment in August 2018.

Minnesota NETT Hub participating hospitals:

  • Hennepin County Medical Center
  • University of Kansas Medical Center
  • University of Minnesota Medical Center - Fairview

POINT - Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial

POINT is a randomized, double-blind, multicenter trial to determine whether clopidogrel 75mg/day (after a loading dose of 600mg) is effective in improving survival free from major ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death) at 90 days when initiated within 12 hours time last known free of new ischemic symptoms of TIA or minor ischemic stroke in subjects receiving aspirin 50-325mg/day.

The POINT trial was completed March of 2018, the published results were presented at the European Stroke Conference in May 2018. The published article can be found here.

Minnesota NETT Hub participating hospitals:

  • Abbott Northwestern Hospital
  • Hennepin County Medical Center
  • Mayo Clinic
  • Regions Hospital
  • United Hospital
  • University of Kansas Medical Center
  • University of Minnesota Medical Center - Fairview

ALIAS

Stroke is the leading cause of death and disability in the United States. The purpose of the ALIAS (Albumin in Acute Stroke) trial is to evaluate the effectiveness of high-dose, intravenous human serum albumin.  Human serum albumin is a natural protein already in clinical use for a variety of indication. In animal laboratory studies it has been shown that it reduces the size of the infarction (amount of tissue death) in the brain and improves neurological function after a stroke and also decreases or eliminates the brain swelling that may occur; these effects may reduce or prevent the brain damage resulting from a stroke in humans. Learn more about the ALIAS trial.

Minnesota NETT Hub participating hospitals:

  • Fairview Southdale Hospital
  • Hennepin County Medical Center
  • University of Minnesota Medical Center - Fairview

ATACH-II

Antihypertenseive Treatment of Cerebral Hemorrhage is an international trial of very early blood pressure lowering with IV nicardipine to two different systolic blood pressure targets in hypertensive patients with moderate sized parenchymal intracerebral hemorrhage. Learn more about the ATACH-II trial.

Minnesota NETT Hub participating hospitals:

  • Essentia Health - Duluth

  • Fairview Southdale Hospital

Community VOICES (3)

The Community VOICES on informed consent in emergency situation trial reports and anaylzes the various methods of implementing exception from informed consent trials, from trial start up to close. VOICES is currently the only non-interventional, non-NETT trial in the Department of Emergency Medicine. Learn more about the VOICES trial.

ProTECT

Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide. With the exception of mannitol, no therapy has been found to be effective in reducing mortality and improving functional outcomes. Progesterone is a steroid found to have powerful neuroprotective properties in multiple animal models of brain injury. Based on encouraging pilot clinical trial results, the ProTECT (Progesterone for Traumatic Brain Injury: Experimental Clinical Treatment) trial was designed to determine the efficacy and confirm safety of this treatment in adults with moderate to severe TBI. Patients were enrolled into this study within 4 hours of injury. This study was conducted exclusively at Level 1 Trauma Centers. Learn more about the ProTECT trial.

Minnesota NETT Hub participating hospitals:

  • Hennepin County Medical Center
  • North Memorial Medical Center
  • Regions Hospital

RAMPART

Status epilepticus, a condition of persistent seizures that do not stop, is a neurologic emergency associated with death and significant disability. Paramedics treat status epilepticus with anti-seizure medicine, but giving medicine through a vein can be difficult or slow in a seizing patient. This study will determine (1) if the anti-seizure drug midazolam given as a shot in the muscle stops seizures as well as the anti-seizure medicine lorazepam given directly into a vein, and (2) the rapidity and safety of these two medicines given in these different ways.

Patient enrollment began on Monday July 20, 2009 within the Hennepin EMS service only. EMS personnel responding to calls for patients with Status Epilepticus were trained in the RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) protocol and evaluated patients for possible enrollment in this emergency medicine research study. Enrollment was completed January 2011. This study's results were published in the New England Journal of Medicine, February 16, 2012, entitled: Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus. Learn more about the RAMPART trial.

Minnesota NETT Hub participating hospitals:

  • Abbott Northwestern Hospital
  • Fairview Southdale Hospital
  • Hennepin County Medical Center
  • Park Nicollet Methodist Hospital
  • University of Minnesota Medical Center - Fairview

ESETT

Results of the Established Status Epilepticus Treatment Trial (ESETT).

Results published in the November 28, 2019 issue of the New England Journal of Medicine show that the three most common treatment options administered in the emergency department for patients who experience refractory status epilepticus: levetiracetam, fosphenytoin and valproate are equally safe and effective in children and adults. The manuscript is available for review at z.umn.edu/esettresults.

The results of ESETT validate the use of the three drugs and give emergency physicians options when it comes to treating patients with refractory status epilepticus. Doctors can be confident that the particular treatment they choose for their patients with status epilepticus is safe and effective and may help them avoid the need to intubate the patient as well as stays in the intensive care unit.

 This was a truly collaborative, multidisciplinary study that involved pediatricians, emergency medicine doctors, neurologists, pharmacologists and biostatisticians all contributing their expertise.

Congratulations and many thanks to all those who were involved!