Grand Rounds January 27, 2023: The PREPARE II Trial: Embedding a Pragmatic Trial Into Clinical Care During an Emergency Procedure (Derek W. Russell, MD; Matthew W. Semler, MD, MSc)

Posted on by Elizabeth Mccamic

Speakers

Derek W. Russell, MD
Assistant Professor, Department of Medicine
Co-Director, Program in Medical ICU Research
Division of Pulmonary, Allergy & Critical Care Medicine
Assistant Medical Director, Birmingham Veterans Affairs Medical Center MICU
University of Alabama at Birmingham Heersink School of Medicine

Matthew W. Semler, MD, MSc
Assistant Professor of Medicine and Biomedical Informatics
Medical Director, Center for Learning Healthcare, Vanderbilt Institute for Clinical and Translational Research
Vanderbilt University Medical Center

 

 

Keywords

Pragmatic Clinical Trials

 

Key Points

  • Emergency Tracheal Intubation is a procedure that 2-5 million adults undergo, 75% of patients are comatose or delirious, and 5% of patients are in cardiac arrest. It is an important procedure and is also challenging to research. There are many choices clinicians must make for every emergency tracheal intubation for which the effect on patient outcomes is unknown. This results in arbitrary variation in clinical care.
  • The PrePARE Trial tested the initiation of a 500 mL crystalloid fluid bolus before induction in 9 U.S. ICUs. The outcome was no benefit from fluid bolus before induction at prevention of cardiovascular collapse. There was an interesting consistent pattern of subgroups of patients who were exposed earlier or more intensive positive pressure ventilation modalities, such as non-invasive ventilation, that was applied earlier in the procedure seemed to have better outcomes. This led to the PREPARE II research question: Does an IV fluid bolus prevent severe hypotension during emergency intubation?
  • PREPARE II is a multi-center, parallel-group, randomized trial conducted from February 2019-May 2021 comparing fluid bolus and no fluid bolus among critically ill adults undergoing tracheal intubation with sedation who were receiving positive pressure ventilation between induction and laryngoscopy at 11 academic ICU sites across the U.S. It was conducted with waiver of informed consent.
  • The trial had 1:1 randomization in blocks of 2, 4, & 6, stratified by site. Sites had envelopes with randomized group assignment that were kept with intubation equipment. Inside the envelop was the study group assignment and instructions to be implemented by clinical personnel for either fluid bolus or no fluid bolus.
  • There was a 1-page data collection sheet that trained site-specific observers completed with rapid feedback from research team on data quality. The data collector was not clinically taking care of the patient but familiar with the procedure and trained on data collection. The initial sample size was 750; the final sample size was 1,065.
  • The occurrence of cardiovascular collapse was 18.2% in the no fluid bolus group and the incidents was 21% in the fluid bolus group. This is an absolute risk difference of 2.8%, which is not a statistically significant difference.
  • In clinical care, patients are receiving treatments that are ineffective (or harmful). Without RCTs we cannot know which treatments are helpful and which are not. Emergency research has largely focused on a small number of conditions and neglected many common treatments, such as intubation. Embedding RCT procedures within emergency care can deliver treatments in the manner that they are delivered in clinical care, collecting data on which clinicians and patients base decisions, and it can enroll diverse and representative trial populations.

Learn more

Read more in JAMA: Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation.

Discussion Themes

– Was there information to the patients so they knew that they were part of the trial? After enrollment, there is an IRB-approved document that includes information on the trial, the investigators, and contact information that patients receive.

– How did you navigate the IRB process? This trial used a mixed approach. Many of the sites used a single IRB but some chose to approve the IRB locally. At Vanderbilt, we did not have any contact internally with the IRB. We had to develop an ethical framework for this for our institution. We provided a lot of data that show treatments are available at all sites and there is already variability by clinicians.

Tags

#pctGR, @Collaboratory1