Septic ShockNCT02473718

Fluid Balance in the ICU - Interventions to Minimize Fluids in Patients With Septic Shock

A study testing Fluid minimization protocol and Ultrasound in people with Septic Shock and Fluid Therapy, run by Washington University School of Medicine.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 89 years
Conditions the study is for: Septic Shock, Fluid Therapy, Hypotension
What is being tested?: Fluid minimization protocol and Ultrasound
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 82 participants
Where: No sites listed yet
Study dates: Jan 2014to Jan 2015
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 to 89 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult patient with septic shock as the primary cause of hypotension
Requiring vasopressors for 12 hours after adequate fluid resuscitation and at the time of enrollment

Who cannot join

Patients with a history of end-stage renal disease requiring outpatient dialysis
Patients whose goals of care are consistent with comfort measures only
Pregnant patients

About this study

The purpose of the study is to determine if a protocol that assesses patients' daily fluid intake and output can decrease the overall amount of fluid patients receive during the first five days in the ICU. The study will also determine if decreasing overall fluids can decrease adverse events associated with mechanical ventilation, such as ventilator-associated pneumonias.

The protocol will include daily ultrasounds and blood draws to evaluate fluid balance. Ultrasound will be used to measure changes in the diameter of the inferior vena cava with respiration.

Conditions: Septic Shock, Fluid Therapy, Hypotension
Being tested: Fluid minimization protocol, Ultrasound
Medical subject headings: Shock, Septic, Hypotension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fluid minimization protocolOther
Fluid nonresponsive patients will have continuous infusions concentrated, maintenance fluids discontinued, and carrier fluids minimized. Diuretics and/or ultrafiltration will be utilized to maintain an even to negative fluid balance in patients demonstrating fluid non-responsiveness.
UltrasoundDevice

Study groups in NCT02473718
Study group	Role	What they receive
Fluid minimization group	Experimental	Patients in the fluid minimization arm will have daily fluid intake and output, baseline central venous pressure, mean arterial pressure, central venous oxygen saturation, pulse pressure variation, and inferior vena cava diameters during inspiration and expiration recorded by a dedicated research fellow. Patients who are intubated will also have corrected flow time, stroke volume, cardiac output, and cardiac index recorded via CardioQ. A fluid challenge in the form of a leg raise or infusion of 250 mL of crystalloid over 5 minutes will then be performed and the parameters repeated. The patient will be judged to be fluid responsive or nonresponsive based on the changes in the parameters. Fluid nonresponsive patients will receive the intervention of the fluid minimization protocol by concentrating continuous infusions, discontinuing maintenance fluids, and minimizing carrier fluids. Diuretics and/or ultrafiltration will be utilized to maintain an even to negative fluid balance. Receives: Other: Fluid minimization protocol; Device: Ultrasound
Usual care group	No intervention	Patients in the usual care arm will have daily fluid intake and output, baseline central venous pressure, mean arterial pressure, central venous oxygen saturation, pulse pressure variation, and inferior vena cava diameters during inspiration and expiration recorded by a dedicated research fellow. Patients who are intubated will also have corrected flow time, stroke volume, cardiac output, and cardiac index recorded via CardioQ.

What is being measured

The primary outcome is the main question the study is designed to answer.

Cumulative Fluid Administered
Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 3
Measured: Day 3
Cumulative Fluid Administered
Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 5
Measured: Day 5
Net Fluid Balance
Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 3
Measured: Day 3
Net Fluid Balance
Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 5
Measured: Day 5

Secondary outcomes (4)

Ventilator Days
Number of days requiring mechanical ventilation support, including continuous noninvasive positive pressure ventilation
Measured: Hospital stay, median of 16 days
Rate of Renal Replacement Therapy
Percentage of patients requiring renal replacement therapy
Measured: ICU stay, median of 10 days
Mortality
Percentage of patients who died during their hospitalization
Measured: Hospital stay, median of 16 days
Mortality
Percentage of patients who died during their ICU stay
Measured: ICU stay, median of 10 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2014Jan 2015

First posted16 Jun 2015 (estimated)
Study startJan 2014
Primary completionDec 2014
Study completionJan 2015

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 (11)Papers the sponsor has linked to this study.
Other trials for Septic ShockStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe 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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 82 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02473718
Sponsor's protocol ID: 201310111
Status last verified: Jul 2024
First submitted: 10 Jun 2015
Last updated: 24 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Alsous F, Khamiees M, DeGirolamo A, Amoateng-Adjepong Y, Manthous CA. Negative fluid balance predicts survival in patients with septic shock: a retrospective pilot study. Chest. 2000 Jun;117(6):1749-54. doi: 10.1378/chest.117.6.1749.
PubMed 10858412
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
PubMed 11445675
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af.
PubMed 23353941
Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, Richard C, Pinsky MR, Teboul JL. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000 Jul;162(1):134-8. doi: 10.1164/ajrccm.162.1.9903035.
PubMed 10903232
Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002 Jun;121(6):2000-8. doi: 10.1378/chest.121.6.2000.
PubMed 12065368
Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008 Jul;134(1):172-8. doi: 10.1378/chest.07-2331.
PubMed 18628220
Marik PE, Baram M. Noninvasive hemodynamic monitoring in the intensive care unit. Crit Care Clin. 2007 Jul;23(3):383-400. doi: 10.1016/j.ccc.2007.05.002.
PubMed 17900477
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
PubMed 11794169
Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a.
PubMed 16424713
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21.
PubMed 16714767
Chen C, Kollef MH. Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A Pilot Study. Chest. 2015 Dec;148(6):1462-1469. doi: 10.1378/chest.15-1525.
PubMed 26291900

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 4
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Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
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ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis

All Septic Shock trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Fluid Balance in the ICU - Interventions to Minimize Fluids in Patients With Septic Shock
ClinicalTrials.gov ID: NCT02473718
Acronym / sponsor ID: 201310111
Conditions: Septic Shock, Fluid Therapy, Hypotension
Study type: Interventional
Recruitment status: Completed
Enrolment: 82 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Study start: Jan 2014
Primary completion: Dec 2014 (actual)
Study completion: Jan 2015 (actual)
First posted: 16 Jun 2015 (estimated)
Results: Posted 29 Mar 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The protocol will include daily ultrasounds and blood draws to evaluate fluid balance. Ultrasound will be used to measure changes in the diameter of the inferior vena cava with respiration.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Fluid minimization group	Experimental	Other: Fluid minimization protocol, Device: UltrasoundPatients in the fluid minimization arm will have daily fluid intake and output, baseline central venous pressure, mean arterial pressure, central venous oxygen saturation, pulse pressure variation, and inferior vena cava diameters during inspiration and expiration recorded by a dedicated research fellow. Patients who are intubated will also have corrected flow time, stroke volume, cardiac output, and cardiac index recorded via CardioQ. A fluid challenge in the form of a leg raise or infusion of 250 mL of crystalloid over 5 minutes will then be performed and the parameters repeated. The patient will be judged to be fluid responsive or nonresponsive based on the changes in the parameters. Fluid nonresponsive patients will receive the intervention of the fluid minimization protocol by concentrating continuous infusions, discontinuing maintenance fluids, and minimizing carrier fluids. Diuretics and/or ultrafiltration will be utilized to maintain an even to negative fluid balance.
Usual care group	No intervention	–Patients in the usual care arm will have daily fluid intake and output, baseline central venous pressure, mean arterial pressure, central venous oxygen saturation, pulse pressure variation, and inferior vena cava diameters during inspiration and expiration recorded by a dedicated research fellow. Patients who are intubated will also have corrected flow time, stroke volume, cardiac output, and cardiac index recorded via CardioQ.

Who may qualify

Ages: 18 to 89 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Adult patient with septic shock as the primary cause of hypotension
Requiring vasopressors for 12 hours after adequate fluid resuscitation and at the time of enrollment

Key exclusion criteria (3 listed)

Patients with a history of end-stage renal disease requiring outpatient dialysis
Patients whose goals of care are consistent with comfort measures only
Pregnant patients

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 minimization protocolFluid nonresponsive patients will have continuous infusions concentrated, maintenance fluids discontinued, and carrier fluids minimized. Diuretics and/or ultrafiltration will be utilized to maintain an even to negative fluid balance in patients demonstrating fluid non-responsiveness.	Other	Fluid minimization group
Ultrasound	Device	Fluid minimization group

Primary outcome

Cumulative Fluid Administered
Time frame: Day 3
Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 3
Cumulative Fluid Administered
Time frame: Day 5
Cumulative volume of crystalloid boluses, continuous infusions, and colloid fluids administered in mL by day 5
Net Fluid Balance
Time frame: Day 3
Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 3
Net Fluid Balance
Time frame: Day 5
Difference between cumulative volume of all IV fluids administered and all outputs in mL by day 5

4 secondary outcomes

Ventilator Days
Time frame: Hospital stay, median of 16 days
Rate of Renal Replacement Therapy
Time frame: ICU stay, median of 10 days
Mortality
Time frame: Hospital stay, median of 16 days
Mortality
Time frame: ICU stay, median of 10 days

Results and safety

Results posted to the registry on 29 Mar 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fluid Minimization Group	41	41
Usual Care Group	41	41

Primary outcome: Cumulative Fluid Administered

Time frame: Day 3. Median (Inter-Quartile Range). Unit: mL of study fluid

Measure	Fluid Minimization Group n = 36	Usual Care Group n = 38
Value	4417 (3139 to 6528)	4110 (2702 to 10004)

Population analysed: Five patients in the fluid minimization group and two patients in the usual care group died prior to the first time point analysis at day three. One patient in the usual care group was transferred out of the ICU prior to the first time point analysis at day 3.

Primary outcome: Cumulative Fluid Administered

Time frame: Day 5. Median (Inter-Quartile Range). Unit: mL of study fluid

Measure	Fluid Minimization Group n = 31	Usual Care Group n = 31
Value	6244 (5106 to 8497)	8690 (4211 to 13197)

Population analysed: Five patients in the fluid minimization group and four patients in the usual care group died prior to analysis at day 5. Five patients in the fluid minimization group and six patients in the usual care group were transferred out of the ICU prior to analysis at day 5.

Primary outcome: Net Fluid Balance

Time frame: Day 3. Median (Inter-Quartile Range). Unit: mL

Measure	Fluid Minimization Group n = 36	Usual Care Group n = 38
Value	1952 (48 to 5003)	3124 (767 to 10103)

Primary outcome: Net Fluid Balance

Time frame: Day 5. Median (Inter-Quartile Range). Unit: mL

Measure	Fluid Minimization Group n = 31	Usual Care Group n = 31
Value	2641 (-1837 to 5075)	3616 (-1513 to 9746)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Hospital length of stay, median of 16 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fluid Minimization Group	0 of 41 (0%)	0 of 41 (0%)	23 of 41
Usual Care Group	0 of 41 (0%)	0 of 41 (0%)	20 of 41

Limitations and caveats (from the sponsor): Pilot study with small sample size Single center study Possible undetected crossover effect or Hawthorne effect

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 10858412Alsous F, Khamiees M, DeGirolamo A, Amoateng-Adjepong Y, Manthous CA. Negative fluid balance predicts survival in patients with septic shock: a retrospective pilot study. Chest. 2000 Jun;117(6):1749-54. doi: 10.1378/chest.117.6.1749.
Background: PubMed 11445675Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
Background: PubMed 23353941Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af.
Background: PubMed 10903232Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, Richard C, Pinsky MR, Teboul JL. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000 Jul;162(1):134-8. doi: 10.1164/ajrccm.162.1.9903035.
Background: PubMed 12065368Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002 Jun;121(6):2000-8. doi: 10.1378/chest.121.6.2000.
Background: PubMed 18628220Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008 Jul;134(1):172-8. doi: 10.1378/chest.07-2331.
Background: PubMed 17900477Marik PE, Baram M. Noninvasive hemodynamic monitoring in the intensive care unit. Crit Care Clin. 2007 Jul;23(3):383-400. doi: 10.1016/j.ccc.2007.05.002.
Background: PubMed 11794169Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
Background: PubMed 16424713Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a.
Background: PubMed 16714767National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21.
Derived from this study: PubMed 26291900Chen C, Kollef MH. Targeted Fluid Minimization Following Initial Resuscitation in Septic Shock: A Pilot Study. Chest. 2015 Dec;148(6):1462-1469. doi: 10.1378/chest.15-1525.

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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.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A study testing Fluid minimization protocol and Ultrasound in people with Septic Shock and Fluid Therapy, run by Washington University School of Medicine.

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 2 inclusion and 3 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 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

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 29 Mar 2018). 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?

Cumulative Fluid Administered (time frame: Day 3). The study lists 4 primary outcomes in all. 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 NCT02473718, which also lists 11 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 24 Jul 2024.