PrePARE: Preventing Cardiovascular collaPse With Administration of Fluid Resuscitation Before Endotracheal Intubation

• Sponsor: Louisiana State University Health Sciences Center in New Orleans (Other)
• Overall Status: Completed
• CT.gov ID: NCT03026777
• Collaborator: (none)
• Enrollment: 337
• Locations: 7
• Arms: 2
• Actual Duration (Months): 12
• Patients Per Site: 48.1
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

Endotracheal intubation is common in the care of critically ill patients. Complications of airway management in this setting are frequently encountered and may be associated with an increased risk of death. The prevention of complications during urgent and emergent endotracheal intubation is a key focus for airway management research. Post-intubation hypotension (PIH), a common complication of endotracheal intubation in the critically ill, may be prevented by a bolus of intravenous fluid prior to the start of the procedure, but this approach has not been examined in a prospective trial. There are no randomized trials of intravenous fluid administration to prevent PIH in critically ill adults. The investigators propose a randomized trial of fluid loading to prevent PIH in critically ill adults.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Failure; Intubation Complication	Drug: intravenous crystalloid fluid, 500 mL	Phase 4

Detailed Description

The investigators propose a randomized, parallel-group trial evaluating the impact of fluid loading to decrease cardiovascular collapse during and after endotracheal intubation in critically ill adults. Patients admitted to the study sites who are deemed by their clinical team to require intubation and fulfill inclusion criteria without meeting exclusion criteria will be enrolled and randomly assigned to intravenous fluid loading versus none. All other decisions regarding airway management will remain at the discretion of the treating provider. Data will be collected at the time of intubation and prospectively from the medical record in order to determine the effect of the assigned intervention on short- and long-term outcomes. All data are collected non-invasively and are already a part of clinical data obtained in usual ICU care at the bedside or in the medical record. No additional data will be collected that is not observed at the bedside or obtained from the medical record.

Study Population: The study population will be all critically ill adults for whom the clinical team has decided to perform endotracheal intubation using sedation with or without neuromuscular blockade. Patients will be excluded only if the operator feels: 1. Additional intravenous fluids in the form of fluid loading is absolutely indicated or contraindicated, or 2. The urgency of the intubation would make performing the study procedures unsafe. Patients will be included regardless of gender, race, weight or body mass index, initial oxygen saturation, anticipated grade of view, and other clinical factors.

Study Interventions:

Fluid Loading - (1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.

No Fluid Loading - No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.

Primary Endpoint:

Cardiovascular collapse - a composite endpoint defined as one or more of the following:

• Death within 1 hour of intubation

• Cardiac arrest within 1 hour of intubation

• New systolic blood pressure < 65 mmHg between induction and 2 minutes after completion of intubation

• New or increased vasopressor receipt between induction and 2 minutes after completion of intubation

Study Design

• Study Type: Interventional
• Actual Enrollment: 337 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Preventing Cardiovascular collaPse With Administration of Fluid Resuscitation Before Endotracheal Intubation: The PrePARE Trial
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluid Loading (1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.	Drug: intravenous crystalloid fluid, 500 mL
No Intervention: Usual Care No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Cardiovascular Collapse [1 hour]

   a composite endpoint defined as one or more of the following: Death within 1 hour of intubation Cardiac arrest within 1 hour of intubation New systolic blood pressure < 65 mmHg between induction and 2 minutes after completion of intubation New or increased vasopressor receipt between induction and 2 minutes after completion of intubation

Secondary Outcome Measures

1. In-hospital Mortality [from date of randomization through study completion, an average of 28 days]

   What was the patient's vital status at the time of hospital discharge

2. Ventilator-free Days [from date of randomization through study completion, an average of 28 days]

   Number of days alive and free of invasive ventilation in a 28-day period

3. ICU-free Days [from date of randomization through study completion, an average of 28 days]

   Number of days alive and outside of an ICU in a 28 day period

4. Lowest Arterial Oxygen Saturation [between induction and 2 minutes following procedure]

   Lowest arterial oxygen saturation between induction and 2 min after intubation

5. Number of Laryngoscopy Attempts [during procedure]

   Number of laryngoscopy attempts to achieve successful tracheal intubation

6. Lowest Systolic Blood Pressure [between induction and 2 minutes following procedure]

   Lowest systolic blood pressure between induction and 2 min after intubation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is admitted to participating study unit

• Planned procedure is endotracheal intubation and planned operator is a provider expected to routinely perform endotracheal intubation in the participating unit

• Administration of sedation with or without neuromuscular blockade is planned

• Age ≥ 18 years old

Exclusion Criteria:

• Operator believes fluid loading to be absolutely indicated or contraindicated for the safe care of the patient

• Urgency of intubation precludes safe performance of study procedures

• Pregnancy

• Prisoners

• Age < 18 years old

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States
2	Ochsner Medical Center	Jefferson	Louisiana	United States	70121
3	LSUHSC and University Medical Center	New Orleans	Louisiana	United States	70112
4	Lahey Medical Center	Burlington	Massachusetts	United States	01805
5	Lincoln Medical Center	Bronx	New York	United States	10451
6	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
7	University of Washington	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Louisiana State University Health Sciences Center in New Orleans

Investigators

• Study Chair: David Janz, MD, MSc, LSU School of Medicine New Orleans

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 8, 2018
• Study Protocol - Dec 8, 2020

More Information

Publications

None provided.

• Responsible Party: David Janz, Assistant Professor of Medicine, Louisiana State University Health Sciences Center in New Orleans
• ClinicalTrials.gov Identifier: NCT03026777
• Other Study ID Numbers: Prepare
• First Posted: Jan 20, 2017
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Additional relevant MeSH terms: Respiratory Insufficiency; Shock

Study Results

Participant Flow

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Period Title: Overall Study
STARTED	168	169
COMPLETED	168	169
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fluid Loading	Usual Care	Total
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.	Total of all reporting groups
Overall Participants	168	169	337
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	61	58	60
Sex: Female, Male (Count of Participants)
Female	81 48.2%	73 43.2%	154 45.7%
Male	87 51.8%	96 56.8%	183 54.3%
Race/Ethnicity, Customized (Count of Participants)
White Race	115 68.5%	121 71.6%	236 70%
Other	53 31.5%	48 28.4%	101 30%
Region of Enrollment (participants) [Number]
United States	168 100%	169 100%	337 100%
Body-mass index (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	27	26	26
Acute physiology and chronic health evaluation score (units on a scale, range 0 to 71) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale, range 0 to 71]	21	20	20

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Cardiovascular Collapse
Description	a composite endpoint defined as one or more of the following: Death within 1 hour of intubation Cardiac arrest within 1 hour of intubation New systolic blood pressure < 65 mmHg between induction and 2 minutes after completion of intubation New or increased vasopressor receipt between induction and 2 minutes after completion of intubation
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

All patients randomized were included in the primary analysis

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Count of Participants [Participants]	33 19.6%	31 18.3%

2. Secondary Outcome

Title	In-hospital Mortality
Description	What was the patient's vital status at the time of hospital discharge
Time Frame	from date of randomization through study completion, an average of 28 days

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Count of Participants [Participants]	48 28.6%	59 34.9%

3. Secondary Outcome

Title	Ventilator-free Days
Description	Number of days alive and free of invasive ventilation in a 28-day period
Time Frame	from date of randomization through study completion, an average of 28 days

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Median (Inter-Quartile Range) [days]	20	19

4. Secondary Outcome

Title	ICU-free Days
Description	Number of days alive and outside of an ICU in a 28 day period
Time Frame	from date of randomization through study completion, an average of 28 days

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Median (Inter-Quartile Range) [days]	16	14

5. Secondary Outcome

Title	Lowest Arterial Oxygen Saturation
Description	Lowest arterial oxygen saturation between induction and 2 min after intubation
Time Frame	between induction and 2 minutes following procedure

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Median (Inter-Quartile Range) [percentage of hemoglobin]	94	95

6. Secondary Outcome

Title	Number of Laryngoscopy Attempts
Description	Number of laryngoscopy attempts to achieve successful tracheal intubation
Time Frame	during procedure

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Median (Inter-Quartile Range) [attempts]	1	1

7. Secondary Outcome

Title	Lowest Systolic Blood Pressure
Description	Lowest systolic blood pressure between induction and 2 min after intubation
Time Frame	between induction and 2 minutes following procedure

Outcome Measure Data

Analysis Population Description

intention to treat

Arm/Group Title	Fluid Loading	Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL	No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
Measure Participants	168	169
Median (Inter-Quartile Range) [mmHg]	119	119

Adverse Events

Time Frame	28 days after enrollment and randomization
Arm/Group Title	Fluid Loading		Usual Care
Arm/Group Description	(1) 500 milliliters of an intravenous crystalloid solution of the operator's choosing will be (2) infused at any time after randomization and prior to the administration of procedural medications from (3) above the level of the central or peripheral intravenous or intraosseus access used and allowed to infuse by gravity and (4) stopped after 500 mL have infused. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered. intravenous crystalloid fluid, 500 mL		No intravenous fluids are started after the decision is made to perform endotracheal intubation. All intravenous infusions preceding the decision to perform endotracheal intubation will not be altered.
All Cause Mortality
	Fluid Loading		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/168 (28.6%)		59/169 (34.9%)
Serious Adverse Events
	Fluid Loading		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/168 (0%)		0/169 (0%)
Other (Not Including Serious) Adverse Events
	Fluid Loading		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/168 (0%)		0/169 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.