Amiodarone, lidocaine or placebo for out-of-hospital cardiac arrest due to ventricular fibrillation or tachycardia — completed October 2015
The goal of ALPS is to determine if survival to hospital discharge is improved with early (and if necessary) repeated therapeutic administration of a new Captisol-Enabled formulation of IV amiodarone (PM101) compared to no antiarrhythmic drug (placebo) or lidocaine. It will compare the benefit of what is believed (but as yet unproven) to be the most effective antiarrhythmic drug (amiodarone) against the traditional standard drug (lidocaine) and against neither (placebo) in shock-resistant cardiac arrest. As such, it will potentially answer 2 critical questions: (1) are antiarrhythmic drugs effective for the treatment of VF cardiac arrest? (2) is amiodarone preferable to lidocaine for such treatment? Answering these questions will determine the proven role (if any) of antiarrhythmic drugs for future generations of patients with out-of-hospital cardiac arrest. Antiarrhythmic medications (amiodarone, lidocaine) are frequently used as part of advanced care to treat ventricular arrhythmias that persist or recur during a cardiac arrest. Although much is known about the pharmacological effects of these drugs, there is a considerable gap in knowledge between our understanding of their mechanisms of action and whether their use actually improves survival after cardiac arrest. No pharmacologic agent has ever been demonstrated to improve survival to hospital discharge after cardiac arrest. It is not known whether these drugs may cause more harm than good. The study will be done at 10 locations across the U.S. and Canada. Almost 70 EMS organizations, involving more than 10,000 EMS providers who serve a combined population of nearly 15 million people from diverse urban, suburban and rural regions will participate in the ROC Continuous Cardiac Compressions study. Approximately 3,000 patients will be enrolled at all of the ROC regions in the United States and Canada. The study is expected to last approximately 3 years. For more information about the completion of the Amiodarone, Lidocaine, Placebo study visit www.clinicaltrials.gov The ClinicalTrials.gov registration number is NCT01401647.
(Continuous Compressions vs Standard CPR) — completed May 28, 2015
The primary aim of the trial is to compare survival at hospital discharge after continuous chest compressions (CCC) versus standard American Heart Association-recommended cardiopulmonary resuscitation with interrupted chest compressions (ICC) in patients with out-of-hospital cardiac arrest. For this study, CCC consists of a series of three cycles of continuous chest compressions without pauses for ventilation followed by rhythm analysis, until restoration of spontaneous circulation or completion of the three cycles of CPR whichever occurs first. ICC consists of series of 3 cycles of standard CPR, each cycle comprised of six sets of 30 chest compressions with interposed ventilations at a compression:ventilation ratio of 30:2 (per AHA guidelines) followed by rhythm analysis until ROSC or three cycles of CPR whichever occurs first. Other aims of the trial are to compare survival to discharge and adverse events between control and intervention groups. The CCC trial will be done at 8 locations across the US and Canada. Almost 125 fire and EMS organizations, involving more than 20,000 fire and emergency medical service (EMS) providers who serve a combined population of nearly 15 million people from diverse urban, suburban and rural regions will participate in the study. Approximately 23,600 patients will be enrolled at all of the ROC regions in the United States and Canada. The study is expected to last approximately 3 years. For more information about the completion of the CCC study see the NHLBI press release here or visit www.clinicaltrials.gov The ClinicalTrials.gov registration number is NCT01372748.
Hypertonic Saline in Traumatic Brain Injury — completed May 12, 2009
A multicenter trial of hypertonic resuscitation in trauma patients with severe traumatic brain injury (TBI) was stopped May 12, 2009. The TBI study sought to determine the impact of hypertonic resuscitation on long term (6 month) neurologic outcome and survival. The study was stopped because it was determined that the hypertonic saline solutions were no better than the standard treatment of normal saline and that it was unlikely that continuing to enroll new patients would change the outcome of the study. There were no concerns about safety. For more information about the closure of the study see the NHLBI press release here or go to clinicaltrials.gov. For more information about traumatic brain injury, visit the website: National Institute of Neurological Disorders and Stroke - Traumatic Brain Injury: Hope Through Research.
Hypertonic Saline in Trauma Patients in Shock — completed February, 2009
A parallel study using the same intervention for blunt or penetrating trauma patients in hypovolemic shock (patients exhibiting low blood pressure) was stopped in February 2009. The shock study sought to determine the impact of hypertonic resuscitation on survival in trauma patients in hypovolemic shock. The trial was stopped because patients who received the concentrated saline solutions were no more likely to survive than those who received a normal saline solution and had earlier, although not increased mortality. For more information about the closure of the HS shock study see the NHLBI press release here or visit www.clinicaltrials.gov.
(Prehospital Resuscitation using an IMpedance valve and Early vs Delayed analysis)
Completed November 6, 2009
ROC PRIMED, a multicenter trial of patients who suffer a cardiac arrest, when the heart abruptly stops outside of the hospital setting, stopped enrollment on November 6, 2009. The trial compared two resuscitation strategies delivered by emergency medical service (EMS) providers to increase blood flow during cardiac arrest. The study's independent monitoring board and the National Heart, Lung, and Blood Institute (NHLBI), the lead sponsor of the study, stopped enrollment based on preliminary data suggesting that neither strategy significantly improved survival. One strategy compared different durations of manual cardiopulmonary resuscitation (CPR) by EMS providers before they assessed whether defibrillation was needed, and the other strategy tested the potential benefits and risks of an investigational device to maintain pressure in the chest during CPR. For more information about the closure of the ROC PRIMED study see the NHLBI press release here or the ROC PRIMED Questions and Answers.
- Ottawa Hospital Research Institute, August 31, 2011
- Vancouver Sun, September 1, 2011
- [http://www.theglobeandmail.com/life/health/new-health/health-news/longer-crp-not-necessarily-beneficial-study/article2149304/|The Globe and Mail, August 31, 2011|]
- Cardiovascular Business, September 1, 2011
- MedPage Today, August 31, 2011
(Prospective Observational Prehospital and Hospital Registry for Trauma)
The primary aims of the PROPHET study are to 1. maintain a comprehensive ongoing data infrastructure to facilitate the design, implementation and interpretation of ROC trauma trials; 2. evaluate the ability of prehospital factors to predict in-hospital measures of injury severity in trauma patients with life threatening injury and 3. evaluate the relationships between prehospital injury characteristics, patient characteristics, EMS and regional structure, processes of care, and outcome in trauma patients with life threatening injury.
Completed November 20, 2009
A multicenter randomized trial to assess whether automated real-time audio-feedback during out-of-hospital cardiopulmonary resuscitation (CPR) would increase return of spontaneous circulation (ROSC) compared to standard CPR alone. Enrollment of 1,521 treated non-traumatic cardiac arrest patients was completed on March 9, 2009. The study was conducted in 21 emergency medical service (EMS) agencies at three ROC regions in the U.S. and Canada. Initial results of the trial were highlighted during the Resuscitation Science Symposium (ReSS) 2009 program. While improved compliance with American Heart Association (AHA) recommendations for CPR performance (time spent doing CPR, rate of compressions, and depth of compressions) improved modestly when feedback was ‘on’, there was no significant difference in ROSC or survival to hospital discharge between the two study groups. Researchers will further analyze and publish the final data in the coming months. For more information about the completion of the CPR Feedback study see the ROC press release here or visit www.clinicaltrials.gov.
Field Trial of Hypotensive Resuscitation versus Standard Resuscitation in Patients with Hemorrhagic Shock after Trauma
Completed April 19, 2013
The traditional treatment of trauma patients is aggressive fluid resuscitation to restore effective circulating volume and systolic blood pressure. Over the last two decades, the practice of aggressively resuscitating hemorrhagic shock utilizing crystalloid has been reexamined because clinical and basic science literature does not support it. Prospective randomized trials have failed to show aggressive early resuscitation or hypotensive resuscitation to be superior in trauma patients. Based on both Advanced Trauma Life Support and Prehospital Trauma Life Support, early aggressive fluid resuscitation remains a cornerstone of the treatment of hemorrhagic shock. In light of the fact that the current standard of care may be harmful and neither strategy has been proven to be superior, the comparison of standard aggressive resuscitation to hypotensive resuscitation is ethical and needed. The primary outcomes of the study will be volume of prehospital and in-hospital fluid administered from time of injury until 2 hours into the hospital stay or until hemorrhage is controlled to test feasibility and 24 hour survival for the safety hypothesis. Secondary outcomes will include measures of protocol adherence, 24 hour fluid volume, 24 hour blood product requirements, ventilator days, hospital length of stay, ICU length of stay, admission base deficit, development of renal failure, admission hematocrit and admission coagulation parameters. The primary goals of this pilot study will be to determine if the described model will result in different early fluid volumes being delivered to the two groups and to determine if these differing volumes impact mortality. If this pilot study shows that hypotensive resuscitation is feasible and safe, a larger trial will be may be conducted. ClinicalTrials.gov number: NCT01411852
(Biomarker Lactate Assessment of Shock in Trauma)
The primary aim of the BLAST study is to compare prehospital lactate levels to systolic blood pressure less than or equal to 90mmHg in ability to predict the need for resuscitative care to treat shock caused by hemorrhage following traumatic injury. This observational study involves the testing of whole blood lactate during out-of-hospital emergency care and repeated testing upon arrival in the hospital’s emergency department using a point of care meter. Blood sampling will be done using a drop of blood discarded in the process of an intravenous catheter insertion by the paramedics at the scene of the incident. The second sample will be obtained during the process of admission lab work blood draws. This has been determined to be a minimal risk study and has been granted a waiver of informed consent. Patient outcomes to be measured are resuscitative care defined as the administration of packed red blood cells, emergent intervention for hemorrhage control using thoracotomy, laparotomy, pelvic fixation or interventional radiologic control of hemorrhage or death within 6 hours of arrival in the emergency department for patients with prehospital systolic blood pressures greater than 70 but less than or equal to 100. The secondary aim is to evaluate the usefulness of point of care lactate when combined with other prehospital variables (age, heart rate, systolic blood pressure, Glasgow Coma Score, mechanism of injury) in predicting the need for resuscitative care.
Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR)
Nearly 50% of trauma deaths occur before the patient reaches the hospital and few of those deaths are preventable. For those that reach the hospital, about 40% experience bleeding complications and require a massive transfusion. Bleeding complications are the leading cause of early death in trauma patients. Studies in both the public and military populations have shown that seriously injured patients who receive a MT with higher plasma ratios had lower mortality than those that received more traditional ratios of plasma. PROPPR is a multicenter, randomized trial which will compare different ratios of blood products given to trauma patients who are predicted to require massive transfusions (MT=greater than 10 units of PRBCs within the first 24 hours). The patients who have been predicted to require a massive transfusion will receive blood products based on a 1:1:1 or 1:1:2 ratio of platelets, plasma and red blood cells. Approximately 580 patients will be enrolled into this study from 12 participating sites in the United States and Canada. In addition to evaluating the patient outcomes based on ratio of products, extensive lab analysis will be done to evaluate the influence of fluid resuscitation on traumatic induced coagulopathy. The PROPPR trial will be conducted under exception from informed consent. The study is expected to last approximately 2 years. ClinicalTrials.gov number: NCT01545232
RESCUE TBI and RESCUE Shock
(Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen-Traumatic Brain Injury (RESCUE-TBI))
(Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen-Traumatic Hemorrhagic Shock (RESCUE-SHOCK))
People admitted to the emergency room at participating hospitals thought to be experiencing or at high risk for traumatic brain injury and/or traumatic hemorrhagic shock are given a single dose of estrogen within 2 hours of injury. Blood samples will be drawn at specific time points over 4 days. Clinical data will also be collected during this time. The primary aim of the RESCUE-SHOCK Pilot Trial is to determine feasibility and safety in order to conduct a larger trial as well as determine whether a single pre-hospital intravenous (IV) dose of PREMARIN® as an initial resuscitation drug improves 28 day survival following traumatic hemorrhagic shock compared to placebo. The ClinicalTrials.gov registration number is NCT00973102. The primary aim of the RESCUE-TBI Trial is to determine feasibility and safety in order to conduct a larger trial as well as determine whether a single pre-hospital IV dose of PREMARIN® as an initial resuscitation drug improves neurologic function using the Galveston Orientation and Amnesia Test (GOAT) following severe traumatic brain injury compared to placebo. The ClinicalTrials.gov registration number is NCT00973674.
(Prehospital Resuscitation On Helicopter Study) — completed December 2015