Acute Respiratory FailurePhase 4PREPARE IINCT03787732
Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation
A Phase 4 study testing Fluid Bolus and No Fluid Bolus in people with Acute Respiratory Failure and Intubation Complication, run by Vanderbilt University Medical Center at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Failure, Intubation Complication, Hypotension on Induction
- What is being tested?
- Fluid Bolus and No Fluid Bolus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,067 participants
- Where
- 11 sitesUnited States
- Study dates
- 1 Feb 2019to 21 Jun 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is undergoing endotracheal intubation in a participating unit
- Planned operator is a provider expected to routinely perform endotracheal intubation in the participating unit
- Patient is at least 18 years of age
- Administration of sedation is planned (with or without neuromuscular blockade)
- Positive pressure ventilation between induction and laryngoscopy is planned (e.g., non-invasive ventilation or bag-mask ventilation)
Who cannot join
- Prisoners
- Pregnant patients
- Urgency of intubation precludes safe performance of study procedures
- Operator feels administration of a fluid bolus is indicated or contraindicated for the safe performance of the procedure
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Lahey Hospital & Medical Center
Burlington, Massachusetts, 01805
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Vanderbilt University Medical Center
Nashville, Tennessee, 37209
Louisiana State University School of Medicine
New Orleans, Louisiana, 70112
Ochsner Medical Center | Ochsner Health System
New Orleans, Louisiana, 70121
Oregon Health & Science University
Portland, Oregon, 97239
University of Washington
Seattle, Washington, 98195
Baylor Scott & White Medical Center - Temple
Temple, Texas, 76508
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II Trial)
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.
Read the 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:
- 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
The secondary outcome is 28-day in-hospital mortality
- Being tested
- Fluid Bolus, No Fluid Bolus
- Keywords
- Intubation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluid BolusDrug
Also called intravenous crystalloid fluid, 500 mL
500 milliliters of an intravenous crystalloid solution of the operator's choosing
No Fluid BolusOther
No additional intravenous crystalloid administration initiated between randomization and two minutes after completion of endotracheal intubation
| Study group | Role | What they receive |
|---|---|---|
| Fluid Bolus | Active comparator | 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. Receives: Drug: Fluid Bolus |
| No Fluid Bolus | Active comparator | 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). Receives: Other: No Fluid Bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiovascular collapse
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
Measured: 1 hour
Secondary outcomes (1)
28-day in-hospital mortality
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start1 Feb 2019
- Primary completion24 May 2021
- Study completion21 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,067 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew Semler, Vanderbilt University Medical Center
- Investigators
- David R Janz, MD, MSCI, Principal investigator, Louisiana State University Health Sciences Center in New OrleansDerek W Russell, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03787732
- Sponsor's protocol ID
- IRB# 181690
- Acronym
- PREPARE II
- Status last verified
- Aug 2021
- First submitted
- 22 Dec 2018
- Last updated
- 12 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Russell DW, Casey JD, Gibbs KW, Ghamande S, Dargin JM, Vonderhaar DJ, Joffe AM, Khan A, Prekker ME, Brewer JM, Dutta S, Landsperger JS, White HD, Robison SW, Wozniak JM, Stempek S, Barnes CR, Krol OF, Arroliga AC, Lat T, Gandotra S, Gulati S, Bentov I, Walters AM, Dischert KM, Nonas S, Driver BE, Wang L, Lindsell CJ, Self WH, Rice TW, Janz DR, Semler MW; PREPARE II Investigators and the Pragmatic Critical Care Research Group. Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial. JAMA. 2022 Jul 19;328(3):270-279. doi: 10.1001/jama.2022.9792.
PubMed 35707974Russell 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.
PubMed 32948554
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II Trial)
- ClinicalTrials.gov ID
- NCT03787732
- Acronym / sponsor ID
- PREPARE II / IRB# 181690
- Keywords
- Intubation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,067 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 24 May 2021 (actual)
- Study completion
- 21 Jun 2021 (actual)
- First posted
- 26 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
The secondary outcome is 28-day in-hospital mortality
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluid Bolus | Active comparator | Drug: Fluid BolusFor 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. |
| No Fluid Bolus | Active comparator | Other: No Fluid BolusFor 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patient is undergoing endotracheal intubation in a participating unit
- Planned operator is a provider expected to routinely perform endotracheal intubation in the participating unit
- Patient is at least 18 years of age
- Administration of sedation is planned (with or without neuromuscular blockade)
- Positive pressure ventilation between induction and laryngoscopy is planned (e.g., non-invasive ventilation or bag-mask ventilation)
Key exclusion criteria (4 listed)
- Prisoners
- Pregnant patients
- Urgency of intubation precludes safe performance of study procedures
- Operator feels administration of a fluid bolus is indicated or contraindicated for the safe performance of the procedure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fluid BolusAlso: intravenous crystalloid fluid, 500 mL500 milliliters of an intravenous crystalloid solution of the operator's choosing | Drug | Fluid Bolus |
| No Fluid BolusNo additional intravenous crystalloid administration initiated between randomization and two minutes after completion of endotracheal intubation | Other | No Fluid Bolus |
Primary outcome
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
1 secondary outcome
28-day in-hospital mortality
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
- Derived from this study: PubMed 35707974Russell DW, Casey JD, Gibbs KW, Ghamande S, Dargin JM, Vonderhaar DJ, Joffe AM, Khan A, Prekker ME, Brewer JM, Dutta S, Landsperger JS, White HD, Robison SW, Wozniak JM, Stempek S, Barnes CR, Krol OF, Arroliga AC, Lat T, Gandotra S, Gulati S, Bentov I, Walters AM, Dischert KM, Nonas S, Driver BE, Wang L, Lindsell CJ, Self WH, Rice TW, Janz DR, Semler MW; PREPARE II Investigators and the Pragmatic Critical Care Research Group. Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial. JAMA. 2022 Jul 19;328(3):270-279. doi: 10.1001/jama.2022.9792.
- Derived from this study: PubMed 32948554Russell 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David R Janz, MD, MSCI principal investigator
Louisiana State University Health Sciences Center in New Orleans
Derek W Russell, MD principal investigator
University of Alabama at Birmingham
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fluid Bolus and No Fluid Bolus in people with Acute Respiratory Failure and Intubation Complication, run by Vanderbilt University Medical Center at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiovascular collapse (time frame: 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03787732, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2021.