SepsisNCT01449721
Preemptive Resuscitation for Eradication of Septic Shock
A study testing Intravenous fluid in people with Sepsis and Severe Sepsis, run by Christiana Care Health Services at 5 sites in United States.
Trial summary
The purpose of this study is to assess the ability of an empiric resuscitation strategy compared to standard care to decrease the incidence of organ failure in normotensive sepsis patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Severe Sepsis
- What is being tested?
- Intravenous fluid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 5 sitesUnited States
- Study dates
- Sep 2011to Jan 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Emergency department patient with suspected or confirmed infection as primary reason for admission
- Serum venous lactate 2.0 - 3.9 mmol/L
- Hospital admission planned
Who cannot join
- Age < 18 years
- Pregnancy
- Serum lactate ≥ 4.0 mmol/L
- Any vasopressor or inotrope requirement
- Mechanical ventilation or non-invasive positive pressure ventilation
- Chronic end-stage renal disease requiring hemodialysis
Show all 10Show fewer
- Pulmonary edema as diagnosed by the primary care team
- Requirement for surgery within the treatment protocol timeframe
- Inability to obtain informed consent from subject or surrogate
- Patient to receive comfort measures only
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Cooper University Hospital:Cooper Medical School of Rowan University
Camden, New Jersey, 08103
Detroit Receiving Hospital/University Health Center
Detroit, Michigan, 48201
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Christiana Care Health System
Newark, Delaware, 19718
About this study
Official title: Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis
The purpose of this study is to assess the ability of an empiric resuscitation strategy compared to standard care to decrease the incidence of organ failure in normotensive sepsis patients.
Read the detailed description
Sepsis is a challenging and elusive entity with a high mortality rate. As a syndrome, clinicians are challenged to distinguish individuals with systemic infection warranting further interventions from lower severity patients. Sepsis is now recognized as a time-sensitive emergency, as patients stand the best chance for survival when effective therapeutic interventions are delivered as early as possible.
Recent data has shown that in-hospital disease progression from sepsis to septic shock is associated with a higher risk of morbidity and mortality than those with shock on initial presentation. Yet, even when identified and treated with early aggressive interventions, the development of septic shock is still associated with a mortality rate of 25-40%.
Although the presence of sustained arterial hypotension or serum lactate elevation (>4.0 mmol/L) are the currently recommended threshold to define the presence of overt shock and the need for aggressive resuscitation, the investigators have shown that, in patients with systemic infection, a moderate lactate elevation (2.0-3.9 mmol/L) is a common occurrence and an important warning sign for the increased risk of disease progression and death. Sepsis with an elevated lactate between 2.0-3.9, referred to as the "PRE-SHOCK" state, identifies this population of patients at-risk for poor outcome. Current guidelines for sepsis management do not recommend any specific resuscitation measures or therapies for this at-risk population. This study marks the first in a series of investigations addressing the PRE-SHOCK population to further define the adverse events within this cohort and to investigate novel interventions to improve outcomes.
The investigators hypothesize that an early quantitative resuscitation strategy using a protocol-directed IV fluid resuscitation will result in a significant reduction in the development of worsening organ failure (including shock) and mortality compared to standard care.
- Conditions
- Sepsis, Severe Sepsis
- Being tested
- Intravenous fluid
- Keywords
- Sepsis, Multiple organ failure, Resuscitation
- Medical subject headings
- Sepsis, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous fluidDrug
Also called Normal saline
0.9% Sodium chloride intravenous fluid
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | Standard medical care by the primary treatment team. |
| Interventional arm | Experimental | Protocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization Receives: Drug: Intravenous fluid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase ≥ 1
Development of worsening organ failure defined by the Sequential Organ Failure Assessment (SOFA) score. The SOFA score defines the presence and severity of dysfunction within 6 organ systems (cardiovascular, respiratory, coagulation, liver, renal, and nervous system) with a value of "0" for assigned to normal function to a maximum value of "4" for severe dysfunction in each of the organ systems. Each component of the SOFA score is added together, ranging from "0" indicating no organ dysfunction in any of the 6 organ systems, to "24" indicating maximal organ dysfunction across all 6 organ systems.
Within this trial, the occurrence of organ failure was defined by any increase in the total SOFA score by ≥ 1 point over the first 72 hours after randomization.
Measured: 72 hours
Secondary outcomes (2)
In-hospital Mortality
Any occurrence of mortality while the participant is in-hospital is counted as an outcome.
Measured: In-hospital discharge or up to maximum 30 days
Number of Participants With Experiencing Complications Related to Intravascular Volume Overload
Composite safety endpoint:
- Premature termination of the protocol-directed intravenous fluid administration by the investigator or primary physician due to presumed volume overload
- Administration of intravenous diuretic for acute pulmonary edema
- Respiratory failure requiring ventilatory assistance (BiPAP, CPAP, or mechanical ventilation) secondary to pulmonary edema per primary care team
Measured: 12 hours following treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2011 (estimated)
- Study startSep 2011
- Primary completionJan 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christiana Care Health Services
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alan Jones, MD, Study chair, University of Mississippi Medical CenterRyan Arnold, MD, Principal investigator, Cooper University Hospital: Cooper Medical School of Rowan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01449721
- Sponsor's protocol ID
- PRESHOCK
- Status last verified
- Oct 2017
- First submitted
- 29 Sep 2011
- Last updated
- 4 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sakr Y, Vincent JL, Schuerholz T, Filipescu D, Romain A, Hjelmqvist H, Reinhart K. Early- versus late-onset shock in European intensive care units. Shock. 2007 Dec;28(6):636-643.
PubMed 18092378Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med. 2009 May;37(5):1670-7. doi: 10.1097/CCM.0b013e31819fcf68.
PubMed 19325467Glickman SW, Cairns CB, Otero RM, Woods CW, Tsalik EL, Langley RJ, van Velkinburgh JC, Park LP, Glickman LT, Fowler VG Jr, Kingsmore SF, Rivers EP. Disease progression in hemodynamically stable patients presenting to the emergency department with sepsis. Acad Emerg Med. 2010 Apr;17(4):383-90. doi: 10.1111/j.1553-2712.2010.00664.x.
PubMed 20370777
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preemptive Empiric Resuscitation Protocol for the Prevention of Disease Progression in the Treatment of Sepsis
- ClinicalTrials.gov ID
- NCT01449721
- Acronym / sponsor ID
- PRESHOCK
- Conditions
- Sepsis, Severe Sepsis
- Keywords
- Sepsis, Multiple organ failure, Resuscitation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Christiana Care Health ServicesUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 10 Oct 2011 (estimated)
- Results
- Posted 4 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the ability of an empiric resuscitation strategy compared to standard care to decrease the incidence of organ failure in normotensive sepsis patients.
Detailed description
Sepsis is a challenging and elusive entity with a high mortality rate. As a syndrome, clinicians are challenged to distinguish individuals with systemic infection warranting further interventions from lower severity patients. Sepsis is now recognized as a time-sensitive emergency, as patients stand the best chance for survival when effective therapeutic interventions are delivered as early as possible.
Recent data has shown that in-hospital disease progression from sepsis to septic shock is associated with a higher risk of morbidity and mortality than those with shock on initial presentation. Yet, even when identified and treated with early aggressive interventions, the development of septic shock is still associated with a mortality rate of 25-40%.
Although the presence of sustained arterial hypotension or serum lactate elevation (>4.0 mmol/L) are the currently recommended threshold to define the presence of overt shock and the need for aggressive resuscitation, the investigators have shown that, in patients with systemic infection, a moderate lactate elevation (2.0-3.9 mmol/L) is a common occurrence and an important warning sign for the increased risk of disease progression and death. Sepsis with an elevated lactate between 2.0-3.9, referred to as the "PRE-SHOCK" state, identifies this population of patients at-risk for poor outcome. Current guidelines for sepsis management do not recommend any specific resuscitation measures or therapies for this at-risk population. This study marks the first in a series of investigations addressing the PRE-SHOCK population to further define the adverse events within this cohort and to investigate novel interventions to improve outcomes.
The investigators hypothesize that an early quantitative resuscitation strategy using a protocol-directed IV fluid resuscitation will result in a significant reduction in the development of worsening organ failure (including shock) and mortality compared to standard care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –Standard medical care by the primary treatment team. |
| Interventional arm | Experimental | Drug: Intravenous fluidProtocolized empiric resuscitation delivering weight-based intravenous fluid resuscitation targeting lactate normalization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Emergency department patient with suspected or confirmed infection as primary reason for admission
- Serum venous lactate 2.0 - 3.9 mmol/L
- Hospital admission planned
Key exclusion criteria (10 listed)
- Age < 18 years
- Pregnancy
- Serum lactate ≥ 4.0 mmol/L
- Any vasopressor or inotrope requirement
- Mechanical ventilation or non-invasive positive pressure ventilation
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 |
|---|---|---|
| Intravenous fluidAlso: Normal saline0.9% Sodium chloride intravenous fluid | Drug | Interventional arm |
Primary outcome
Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase ≥ 1
Time frame: 72 hours
Development of worsening organ failure defined by the Sequential Organ Failure Assessment (SOFA) score. The SOFA score defines the presence and severity of dysfunction within 6 organ systems (cardiovascular, respiratory, coagulation, liver, renal, and nervous system) with a value of "0" for assigned to normal function to a maximum value of "4" for severe dysfunction in each of the organ systems. Each component of the SOFA score is added together, ranging from "0" indicating no organ dysfunction in any of the 6 organ systems, to "24" indicating maximal organ dysfunction across all 6 organ systems. Within this trial, the occurrence of organ failure was defined by any increase in the total SOFA score by ≥ 1 point over the first 72 hours after randomization.
2 secondary outcomes
In-hospital Mortality
Time frame: In-hospital discharge or up to maximum 30 days
Number of Participants With Experiencing Complications Related to Intravascular Volume Overload
Time frame: 12 hours following treatment initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18092378Sakr Y, Vincent JL, Schuerholz T, Filipescu D, Romain A, Hjelmqvist H, Reinhart K. Early- versus late-onset shock in European intensive care units. Shock. 2007 Dec;28(6):636-643.
- Background: PubMed 19325467Mikkelsen ME, Miltiades AN, Gaieski DF, Goyal M, Fuchs BD, Shah CV, Bellamy SL, Christie JD. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med. 2009 May;37(5):1670-7. doi: 10.1097/CCM.0b013e31819fcf68.
- Background: PubMed 20370777Glickman SW, Cairns CB, Otero RM, Woods CW, Tsalik EL, Langley RJ, van Velkinburgh JC, Park LP, Glickman LT, Fowler VG Jr, Kingsmore SF, Rivers EP. Disease progression in hemodynamically stable patients presenting to the emergency department with sepsis. Acad Emerg Med. 2010 Apr;17(4):383-90. doi: 10.1111/j.1553-2712.2010.00664.x.
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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.
Alan Jones, MD study chair
University of Mississippi Medical Center
Ryan Arnold, MD principal investigator
Cooper University Hospital: Cooper Medical School of Rowan University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous fluid in people with Sepsis and Severe Sepsis, run by Christiana Care Health Services at 5 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 3 inclusion and 10 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 4 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Worsening Organ System Dysfunction Defined by SOFA Score Increase ≥ 1 (time frame: 72 hours). 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 NCT01449721, which also lists 3 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 4 Oct 2017.