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

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ClinicalTrials.gov Identifier: NCT03787732
Recruitment Status : Recruiting
First Posted : December 26, 2018
Last Update Posted : December 2, 2020
Sponsor:
Information provided by (Responsible Party):
Matthew Semler, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE December 22, 2018
First Posted Date  ICMJE December 26, 2018
Last Update Posted Date December 2, 2020
Actual Study Start Date  ICMJE February 1, 2019
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2018)
28-day in-hospital mortality [ Time Frame: 28 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 30, 2020)
  • New systolic blood pressure < 65 mmHg between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • New or increased vasopressor between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • Cardiac arrest within 1 hour of intubation [ Time Frame: 1 hour ]
  • Death within 1 hour of intubation [ Time Frame: 1 hour ]
  • Lowest systolic blood pressure between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • Change in systolic blood pressure from induction to lowest systolic blood pressure [ Time Frame: between induction and 2 minutes following procedure ]
  • Ventilator-free days [ Time Frame: 28 days ]
  • ICU-free days [ Time Frame: 28 days ]
  • Lowest oxygen saturation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
    Lowest arterial oxygen saturation between induction and 2 minutes after intubation
  • 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
  • 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
  • Oxygen saturation at 24 hours after intubation [ Time Frame: 24 hours ]
  • Fraction of inspired oxygen at 24 hours after intubation [ Time Frame: 24 hours ]
  • Positive end expiratory pressure at 24 hours after intubation [ Time Frame: 24 hours ]
  • Systolic blood pressure at 24 hours after intubation [ Time Frame: 24 hours ]
  • Additional intravenous fluids initiated between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • Time from induction to successful intubation [ Time Frame: Duration of procedure (minutes) ]
  • Cormack-Lehane grade of glottic view on first attempt [ Time Frame: Duration of procedure (minutes) ]
  • 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.
  • Incidence of successful intubation on the first laryngoscopy attempt [ Time Frame: Duration of procedure (minutes) ]
  • Number of laryngoscopy attempts [ Time Frame: Duration of procedure (minutes) ]
  • Need for additional airway equipment or a second operator [ Time Frame: Duration of procedure (minutes) ]
Original Other Pre-specified Outcome Measures
 (submitted: December 22, 2018)
  • New systolic blood pressure < 65 mmHg between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • New or increased vasopressor between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • Cardiac arrest within 1 hour of intubation [ Time Frame: 1 hour ]
  • Death within 1 hour of intubation [ Time Frame: 1 hour ]
  • Lowest systolic blood pressure between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • Change in systolic blood pressure from induction to lowest systolic blood pressure [ Time Frame: between induction and 2 minutes following procedure ]
  • Vasopressor-free days [ Time Frame: 28 days ]
  • Ventilator-free days [ Time Frame: 28 days ]
  • ICU-free days [ Time Frame: 28 days ]
  • Lowest oxygen saturation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
    Lowest arterial oxygen saturation between induction and 2 minutes after intubation
  • 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
  • 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
  • Oxygen saturation at 24 hours after intubation [ Time Frame: 24 hours ]
  • Fraction of inspired oxygen at 24 hours after intubation [ Time Frame: 24 hours ]
  • Positive end expiratory pressure at 24 hours after intubation [ Time Frame: 24 hours ]
  • Systolic blood pressure at 24 hours after intubation [ Time Frame: 24 hours ]
  • Additional intravenous fluids initiated between induction and 2 minutes after intubation [ Time Frame: from induction to 2 minutes following tracheal intubation ]
  • Time from induction to successful intubation [ Time Frame: Duration of procedure (minutes) ]
  • Cormack-Lehane grade of glottic view on first attempt [ Time Frame: Duration of procedure (minutes) ]
  • Operator-assess difficulty of intubation [ Time Frame: Duration of procedure (minutes) ]
  • Incidence of successful intubation on the first laryngoscopy attempt [ Time Frame: Duration of procedure (minutes) ]
  • Number of laryngoscopy attempts [ Time Frame: Duration of procedure (minutes) ]
  • Need for additional airway equipment or a second operator [ Time Frame: Duration of procedure (minutes) ]
 
Descriptive Information
Brief Title  ICMJE Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation
Official Title  ICMJE Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II Trial)
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.
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Acute Respiratory Failure
  • Intubation Complication
  • Hypotension on Induction
Intervention  ICMJE
  • Drug: Fluid Bolus
    500 milliliters of an intravenous crystalloid solution of the operator's choosing
    Other Name: intravenous crystalloid fluid, 500 mL
  • Other: No Fluid Bolus
    No additional intravenous crystalloid administration initiated between randomization and two minutes after completion of endotracheal intubation
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Fluid Bolus
  • 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).
    Intervention: Other: No Fluid Bolus
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 30, 2020)
1065
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2018)
750
Estimated Study Completion Date  ICMJE October 1, 2021
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03787732
Other Study ID Numbers  ICMJE IRB# 181690
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Matthew Semler, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Vanderbilt University Medical Center
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP