Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II)

• ClinicalTrials.gov Identifier: NCT03787732
• Recruitment Status: Recruiting
• First Posted: December 26, 2018
• Last Update Posted: November 27, 2019
• Sponsor: Vanderbilt University Medical Center
• Information provided by (Responsible Party): Matthew Semler, Vanderbilt University Medical Center

Study Description

Brief Summary:

Complications are common during tracheal intubation of critically ill patients. Nearly one in five patients undergoing intubation in the intensive care unit experiences cardiovascular collapse, defined as severe hypotension, vasopressor administration, cardiac arrest or death. Cardiovascular collapse during intubation is associated with increased resource utilization and decreased survival. Administration of 500 mL of intravenous crystalloid solution beginning prior to induction may prevent cardiovascular collapse. The only prior trial examining fluid bolus administration during intubation found no effect on cardiovascular collapse or clinical outcomes overall, but a hypothesis-generating subgroup analysis suggested potential benefit to fluid bolus administration among patients receiving positive pressure ventilation between induction and laryngoscopy. Therefore, we propose a randomized trial comparing fluid bolus administration versus none with regard to cardiovascular collapse among critically adults undergoing intubation with positive pressure ventilation between induction and laryngoscopy.

Condition or disease	Intervention/treatment	Phase
Acute Respiratory Failure; Intubation Complication; Hypotension on Induction	Drug: Fluid Bolus; Other: No Fluid Bolus	Phase 4

Detailed Description:

The PREPARE II trial is a prospective, parallel group, pragmatic, randomized trial comparing the effect of a preintubation fluid bolus to no preintubation fluid bolus on the incidence of cardiovascular collapse during and after endotracheal intubation in critically ill adults.

Patients admitted to the study units who are deemed by their clinical team to require intubation and fulfill inclusion criteria without meeting exclusion criteria will be randomized 1:1 to receive either an intravenous fluid bolus or no intravenous fluid bolus. All other decisions regarding airway management will remain at the discretion of the treating provider. The trial will enroll 750 patients. Conduct of the trial will be overseen by a Data Safety Monitoring Board. An interim analysis will be performed after the enrollment of 375 patients. The analysis of the trial will be conducted in accordance with a pre-specified statistical analysis plan, which will be submitted for publication or made publicly available prior to the conclusion of enrollment.

The primary outcome is cardiovascular collapse - a composite endpoint defined as one or more of the following:

1. Death within 1 hour of intubation
2. Cardiac arrest within 1 hour of intubation
3. New systolic blood pressure < 65 mmHg between induction and 2 minutes after completion of intubation
4. New or increased vasopressor receipt between induction and 2 minutes after completion of intubation

The secondary outcome is 28-day in-hospital mortality

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 750 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II Trial)
• Actual Study Start Date: February 1, 2019
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: September 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Fluid Bolus; For patients randomized to fluid bolus administration, the bedside nurse will obtain 500 mL of a crystalloid solution of the operator's choosing, connect this volume to intravenous infusion tubing, and attach the tubing to any intravenous catheter or intraosseous device. The crystalloid solution will then be placed above the level of the intravenous or intraosseous device and allowed to infuse by gravity or pressure bag. At any time after the initiation of fluid bolus administration, the operator can choose to begin the procedure by administering sedation. Fluid loading will continue until all 500 mL are infused. Fluid infusing prior to the decision to perform endotracheal intubation will not be altered by the current study.	Drug: Fluid Bolus; 500 milliliters of an intravenous crystalloid solution of the operator's choosing; Other Name: intravenous crystalloid fluid, 500 mL
Active Comparator: No Fluid Bolus; For patients randomized to no fluid bolus administration, no additional intravenous crystalloid administration will be initiated between randomization and two minutes after completion of endotracheal intubation. Fluid infusing prior to the decision to perform endotracheal intubation will not be affected by the study. Treating clinicians may initiate a fluid bolus at any time for the treatment of cardiovascular collapse (not considered a protocol violation). Treating clinicians may also initiate a fluid bolus at any time if felt to be mandatory for the safe treatment of the patient (if between randomization and two minutes after intubation and in the absence of cardiovascular collapse this will be recorded as a protocol violation).	Other: No Fluid Bolus; No additional intravenous crystalloid administration initiated between randomization and two minutes after completion of endotracheal intubation

Outcome Measures

Primary Outcome Measures :

1. Cardiovascular collapse [ Time Frame: 1 hour ]

   A composite endpoint defined as one or more of the following

   • New systolic blood pressure < 65 mmHg between induction and 2 minutes after intubation
   • New or increased vasopressor between induction and 2 minutes after intubation
   • Cardiac arrest within 1 hour of intubation
   • Death within 1 hour of intubation

Secondary Outcome Measures :

1. 28-day in-hospital mortality [ Time Frame: 28 days ]

Other Outcome Measures:

1. New systolic blood pressure < 65 mmHg between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
2. New or increased vasopressor between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
3. Cardiac arrest within 1 hour of intubation [ Time Frame: 1 hour ]
4. Death within 1 hour of intubation [ Time Frame: 1 hour ]
5. Lowest systolic blood pressure between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
6. Change in systolic blood pressure from induction to lowest systolic blood pressure [ Time Frame: between induction and 2 minutes following procedure ]
7. Vasopressor-free days [ Time Frame: 28 days ]
8. Ventilator-free days [ Time Frame: 28 days ]
9. ICU-free days [ Time Frame: 28 days ]
10. Lowest oxygen saturation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
    Lowest arterial oxygen saturation between induction and 2 minutes after intubation
11. Incidence of hypoxemia [ Time Frame: from induction to 2 minutes following tracheal intubation ]
    Incidence of oxygen saturation < 90% between induction and 2 minutes after intubation
12. Incidence of severe hypoxemia [ Time Frame: from induction to 2 minutes following tracheal intubation ]
    Incidence of oxygen saturation < 80% between induction and 2 minutes after intubation
13. Oxygen saturation at 24 hours after intubation [ Time Frame: 24 hours ]
14. Fraction of inspired oxygen at 24 hours after intubation [ Time Frame: 24 hours ]
15. Positive end expiratory pressure at 24 hours after intubation [ Time Frame: 24 hours ]
16. Systolic blood pressure at 24 hours after intubation [ Time Frame: 24 hours ]
17. Additional intravenous fluids initiated between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
18. Time from induction to successful intubation [ Time Frame: Duration of procedure (minutes) ]
19. Cormack-Lehane grade of glottic view on first attempt [ Time Frame: Duration of procedure (minutes) ]
20. Difficulty of intubation [ Time Frame: Duration of procedure (minutes) ]
    Operator-reported difficulty of intubation on a three-point ordinal scale of: easy, moderate, or difficult.
21. Incidence of successful intubation on the first laryngoscopy attempt [ Time Frame: Duration of procedure (minutes) ]
22. Number of laryngoscopy attempts [ Time Frame: Duration of procedure (minutes) ]
23. Need for additional airway equipment or a second operator [ Time Frame: Duration of procedure (minutes) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient is undergoing endotracheal intubation in a participating unit
2. Planned operator is a provider expected to routinely perform endotracheal intubation in the participating unit
3. Patient is at least 18 years of age
4. Administration of sedation is planned (with or without neuromuscular blockade)
5. Positive pressure ventilation between induction and laryngoscopy is planned (e.g., non-invasive ventilation or bag-mask ventilation)

Exclusion Criteria:

1. Prisoners
2. Pregnant patients
3. Urgency of intubation precludes safe performance of study procedures
4. Operator feels administration of a fluid bolus is indicated or contraindicated for the safe performance of the procedure

Contacts and Locations

Contacts

Contact: Jonathan D Casey, MD; (615) 208-6139; Jonathan.d.Casey@vumc.org

Contact: Matthew W. Semler, MD, MSc; (615) 802-8428; matthew.w.semler@vumc.org

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35233

Contact: Derek W Russell, MD 205-975-3718 dwrussell@uabmc.edu

United States, Louisiana

Louisiana State University School of Medicine; Recruiting

New Orleans, Louisiana, United States, 70112

Contact: David R Janz, MD, MSc 504-568-3167 djanz@lsuhsc.edu

Ochsner Medical Center | Ochsner Health System; Recruiting

New Orleans, Louisiana, United States, 70121

Contact: Kevin M Dischert, MD kevin.dischert@ochsner.org

Contact: Derek J Vonderhaar, MD dvonde@lsuhsc.edu

United States, Massachusetts

Lahey Hospital & Medical Center; Recruiting

Burlington, Massachusetts, United States, 01805

Contact: James Dargin, MD james.m.dargin@lahey.org

Contact: Sue Stempek, PA-C susan.b.stempek@lahey.org

United States, Minnesota

Hennepin County Medical Center; Recruiting

Minneapolis, Minnesota, United States, 55415

Contact: Matthew Prekker, M.D., MPH prek0003@umn.edu

Contact: Brian Driver Brian.Driver@hcmed.org

United States, Mississippi

University of Mississippi Medical Center; Recruiting

Jackson, Mississippi, United States, 39216

Contact: Joseph M Brewer, DO jmbrewer2@umc.edu

United States, North Carolina

Wake Forest Baptist Medical Center; Recruiting

Winston-Salem, North Carolina, United States, 27157

Contact: Kevin Gibbs kgibbs@wakehealth.edu

United States, Oregon

Oregon Health & Science University; Recruiting

Portland, Oregon, United States, 97239

Contact: Akram Khan, M.D. khana@ohsu.edu

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37209

Contact: Jonathan D Casey, MD 615-322-3412 jonathan.d.casey@vanderbilt.edu

Contact: Matthew W Semler, MD, MSc 615-802-8428 matthew.w.semler@vanderbilt.edu

United States, Texas

Baylor Scott & White Medical Center - Temple; Recruiting

Temple, Texas, United States, 76508

Contact: Shekhar Ghamande, MD Shekhar.Ghamande@BSWHealth.org

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98195

Contact: Aaron M Joffe, DO joffea@uw.edu

Sponsors and Collaborators

Vanderbilt University Medical Center

Investigators

• Principal Investigator: David R Janz, MD, MSCI; Louisiana State University Health Sciences Center in New Orleans
• Principal Investigator: Derek W Russell, MD; University of Alabama at Birmingham

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Russell DW, Casey JD, Gibbs KW, Dargin JM, Vonderhaar DJ, Joffe AM, Ghamande S, Khan A, Dutta S, Landsperger JS, Robison SW, Bentov I, Wozniak JM, Stempek S, White HD, Krol OF, Prekker ME, Driver BE, Brewer JM, Wang L, Lindsell CJ, Self WH, Rice TW, Semler MW, Janz D; PREPARE II Investigators. Protocol and statistical analysis plan for the PREventing cardiovascular collaPse with Administration of fluid REsuscitation during Induction and Intubation (PREPARE II) randomised clinical trial. BMJ Open. 2020 Sep 18;10(9):e036671. doi: 10.1136/bmjopen-2019-036671.

• Responsible Party: Matthew Semler, Assistant Professor of Medicine, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT03787732
• Other Study ID Numbers: IRB# 181690
• First Posted: December 26, 2018
• Last Update Posted: November 27, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Matthew Semler, Vanderbilt University Medical Center:

Intubation

Additional relevant MeSH terms:

Respiratory Insufficiency; Hypotension; Shock; Respiration Disorders; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes