Current Clinical Trials
- Patterns of Survivors' Recovery Trajectories in the ICECAP Trial (POST-ICECAP)
Many patients now survive out-of-hospital cardiac arrest (OHCA), however, gaps in knowledge about long-term outcomes result in a fragmented and underdeveloped continuum of care to achieve recovery. Recovery is defined as significant improvement in functional and cognitive outcomes, and health- related quality of life (HRQoL). OHCA Survivors with favorable recovery patterns may potentially go back to work and/or social roles. Prior studies assessing recovery domains after OHCA are small, limited to single centers, and short-term outcomes i.e., 1-3 months. Identifying individual patient patterns of recovery over longer-term, and the ability to predict who will be likely to need more intensive support after discharge would allow interventions to be targeted more efficiently. It is also crucial that we offer patients and their families the best information available about a patient's prospects for continued recovery even in the absence of modifiable intervention targets.
This study will be among the first to focus on a new equitable science of OHCA survivorship itself, seeking empirically derived targets for preserving or restoring recovery. Our single-center pilot study has found that nearly one-third of the OHCA survivors had clinically important differences between long-term (12 months) and short-term (3 months) functional outcomes with large between-individual variability in recovery (i.e., improvement or worsening). We found that inpatient acute rehabilitation was associated with better functional recovery patterns at 12 months compared to other dispositions, but Black race and Hispanic/Latinx had worse recovery patterns than non-Hispanic Whites. To fill this gap, we propose an ancillary study to the NINDS/NHLBI-funded ICECAP trial, conducted within the 60 sites of the NIH emergency care trials network, to describe recovery (functional outcome [primary], Cognition, and HRQoL outcomes [secondary]) in a large, well-characterized, racially/ethnically diverse, representative cohort of US OHCA patients.
We will enroll 1,000 who were screened for ICECAP and survive to hospital discharge. The parent ICECAP trial includes a telephone follow-up visit at 1 month and an in-person visit at 3 months. The ancillary study will add two telephone/videoconferencing visits at 6 and 9 months and an in-person visit at 12 months after OHCA. For Aim 1, we will describe between-patient variability in recovery (i.e., improvement in functional, cognitive, and HRQoL outcomes) from 3 to 12 months after OHCA, and test whether changes are associated with illness severity scores, and critical care interventions performed during the acute care stay. Aim 2 will test whether receipt of acute inpatient rehabilitation (vs outpatient therapy/no therapy/skilled nursing facility) within 1 month of hospital discharge is associated with greater improvement in recovery outcomes from 3 to 12 months. Finally, in Aim 3, we will test whether non-Hispanic Black and Hispanic/Latinx patients have less favorable changes in recovery outcomes between 3 and 12 months and explore mechanisms for such disparities.
Principal Investigator: Clifton Callaway, MD, PhD
Site Principal Investigator: Kelly Sawyer, MD, MS
- The Effect of SPecialty cAre on Recovery From Cardiac Arrest Trial (the SPARC Trial)
Cardiac arrest is a sudden stopping of the heart, which can sometimes be reversed by rapid cardiopulmonary resuscitation (CPR) and emergency medical care. Each year, over 150,000 Americans are admitted to the hospital after receiving CPR. However, many of these patients die in the hospital. There is wide variation in patient outcomes between hospitals. A key knowledge gap about systems of care is whether specific hospital or subsequent interventions or processes of care are associated with better patient outcomes. Specifically, it is unknown if patient outcomes are improved by specialized centers or by improved implementation of recommended interventions at all hospitals.
Observational data in our region and internationally suggest that out-of-hospital cardiac arrest outcomes are better when patients who survive CPR are hospitalized in specialty care or high-volume centers. It is unclear from these studies what are the minimal capabilities that distinguish specialty care from usual care and which aspects of specialty care are influencing outcomes.
This trial will take advantage of a regional system of care that includes 18 hospitals in southwestern Pennsylvania that treat over 1,000 patients resuscitated from out-of-hospital cardiac arrest annually. This region includes one high-volume specialty center with specific attention to recommended interventions for this patient population, as well as several secondary and tertiary care facilities with variable resources and approaches to patient care. This randomized trial will compare outcomes for patients assigned to care at the specialty center versus other centers and will leverage the heterogeneity of treatment between centers to understand the influence of specific treatments.
Principal Investigator: Jonathan Elmer, MD, MS
Project Manager: Sara DiFiore-Sprouse, MS
Select Completed Clinical Trials
We have leveraged our local research infrastructure and expertise to lead or contribute to multiple clinical trials conducted through the Resuscitation Outcomes Consortium (ROC), the Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN), and other local, national and international research collaborations.
Selected completed trials include:
The Inhaled Nitric Oxide After Out-of-Hospital Cardiac Arrest (iNOOHCA) trial enrolled comatose adult survivors of out-of-hospital cardiac arrest and compared inhaled nitric oxide (iNO) 20 ppm administered over 12h versus placebo. The trial is completed but results are not yet published.
The TTM2 trial enrolled comatose adult survivors of out‑of‑hospital cardiac arrest and compared targeted hypothermia at 33 °C with targeted normothermia/fever prevention. The major finding was that hypothermia did not reduce mortality or improve neurological outcomes compared with active fever prevention.
The ROC Continuous vs Interrupted Compressions (CCC) trial enrolled adults with non‑traumatic out‑of‑hospital cardiac arrest and compared continuous chest compressions with asynchronous ventilations to the standard 30:2 compression‑to‑ventilation strategy. The major finding was no significant difference in survival to discharge or favorable neurological outcomes between strategies.
The ROC ALPS trial enrolled adults with shock‑refractory ventricular fibrillation/pulseless VT during out‑of‑hospital cardiac arrest and compared amiodarone, lidocaine, and placebo. The major finding was no overall improvement in survival to discharge or neurological outcome with antiarrhythmics versus placebo, though a benefit from amiodarone was observed in the subgroup with witnessed arrest.
The ROC PRIMED “Analyze Early vs Analyze Later” trial enrolled adults with out‑of‑hospital cardiac arrest and compared brief versus longer initial CPR before rhythm analysis. The major finding was that timing of the first rhythm analysis did not change survival with good functional outcome.
The ROC PRIMED Impedance Threshold Device (ITD) trial enrolled adults with out‑of‑hospital cardiac arrest and compared an active ITD versus a sham device during standard CPR. The major finding was that use of the ITD did not improve survival with favorable neurological function.
The Continuous Neuromuscular Blockade after Cardiac Arrest trial randomized comatose post‑arrest patients undergoing temperature management to 24 h continuous neuromuscular blockade versus usual care. The trial found no improvement in lactate clearance, survival, or neurological outcomes with routine continuous paralysis.
The Amantadine after Cardiac Arrest trial was a multicenter, randomized, double‑blind, placebo‑controlled pilot that enrolled comatose resuscitated patients to test whether amantadine accelerates awakening. The trial did not demonstrate improved awakening or clinical outcomes with amantadine versus placebo.
The ICECAP trial enrolled comatose adult survivors of out‑of‑hospital cardiac arrest and compared different durations of targeted temperature management using a response‑adaptive design to identify the optimal cooling duration. The trial is completed but results are not yet published.