SepsisBALANCENCT02159079
A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study)
A study testing Conservative Fluid Management Strategy in people with Sepsis, run by Vanderbilt University at 1 site in United States.
Trial summary
Sepsis is a common inflammatory response to infection characterized by hypovolemia and vasodilation for which early administration of intravenous fluids has been suggested to improve outcomes. The ideal fluid balance following initial resuscitation is unclear. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Conservative Fluid Management Strategy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Apr 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
- ICU patients
- Adults
- Sepsis as defined by at least two systemic inflammatory response syndrome criteria and receipt of antimicrobial therapy
- Cardiopulmonary dysfunction as defined shock or respiratory failure
Who cannot join
- Inability to obtain consent
- Greater than 48 hours since inclusion criteria initially met
- Allergy to furosemide AND bumetanide
- Rhabdomyolysis with creatinine kinase > 5000 U/L
- Hypercalcemia with calcium >11 mg/dL
- Diabetic Ketoacidosis requiring continuous insulin infusion
Show all 22Show fewer
- Tumor Lysis Syndrome diagnosed clinically
- Pancreatitis diagnosed clinically
- Chronic Hypoxic Respiratory Failure with Home Oxygen Use of FiO2≥0.3
- Chronic ventilator dependence
- cervical spinal cord injury at level C5 or higher
- amyotrophic lateral sclerosis
- Guillain-Barré Syndrome
- myasthenia gravis
- Renal failure requiring renal replacement therapy
- Burns >20% of body surface area
- Pregnant
- Preexisting pulmonary hypertension with PAPmean>40 on RHC
- Severe chronic liver disease with Childs-Pugh Score >11
- Moribund and not expected to survive an additional 24 hours
- Actively withdrawing life support or transitioning to comfort measures only
- Unwillingness of treating physician to employ conservative fluid strategy
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: A Phase II/III Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction
Sepsis is a common inflammatory response to infection characterized by hypovolemia and vasodilation for which early administration of intravenous fluids has been suggested to improve outcomes. The ideal fluid balance following initial resuscitation is unclear. Septic patients treated in the intensive care unit commonly receive significant volumes of intravenous fluids with resultant positive fluid balance for up to a week after their initial resuscitation. Observational studies have associated fluid receipt and positive fluid balance in patients with severe sepsis and septic shock with increased mortality but are inherently limited by indication bias. In order to determine the optimal approach to fluid management following resuscitation in patients with severe sepsis and septic shock, a randomized controlled trial is needed. The primary hypothesis of this study is that, compared to usual care, a conservative approach to fluid management after resuscitation in patients with sepsis and cardiopulmonary dysfunction will increase intensive care unit free days.
- Conditions
- Sepsis
- Being tested
- Conservative Fluid Management Strategy
- Keywords
- Sepsis, Severe Sepsis, Septic Shock, Conservative Fluid Management, Fluid Balance, Fluid Restriction
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conservative Fluid Management StrategyOther
For patients in the conservative fluid management arm, beginning 12 hours after admission to study ICU and ending at the first of ICU discharge, death, return to home inspired oxygen, or study day 14, fluid management will be controlled by a study protocol. Patients in shock will receive fluid boluses only as specified by the protocol for oliguria and rapidly increasing vasopressor requirement. Patients not in shock will receive fluid boluses only as specified by the protocol for oliguria. Output will exceed input each day using a diuretic drip if required. Study protocol will be held only for pre-specified Safety Endpoints of persistent oliguria, decompensating shock, diuretic side effect, and intervening acute event.
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | No intervention | Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel. |
| Conservative Fluid Management Strategy | Experimental | For patients in the conservative fluid management arm, beginning 12 hours after admission to study ICU and ending at the first of ICU discharge, death, return to home inspired oxygen, or study day 14, fluid management will be controlled by a study protocol. Patients in shock will receive fluid boluses only as specified by the protocol for oliguria and rapidly increasing vasopressor requirement. Patients not in shock will receive fluid boluses only as specified by the protocol for oliguria. Output will exceed input each day using a diuretic drip if required. Study protocol will be held only for pre-specified Safety Endpoints of persistent oliguria, decompensating shock, diuretic side effect, and intervening acute event. Receives: Other: Conservative Fluid Management Strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
ICU-free Days to 14 Days After Enrollment
The primary outcome will be the number of ICU-free days to day 14 (defined as the number days alive and outside of the intensive care unit in the first 14 days after enrollment).
Measured: 14 days
Secondary outcomes (6)
Ventilator-free Days to Day 14
A secondary outcome will be the number of ventilator-free days (defined as the number of days alive and breathing unassisted after the final achievement of unassisted breathing before day 14)
Measured: 14 days
In-hospital Mortality to Day 14
A secondary outcome will be in-hospital mortality to day 14 (defined as the incidence of mortality prior to hospital discharge within 14 days after enrollment).
Measured: 14 days
Renal Replacement Therapy-free Days to Day 14
Renal replacement therapy-free days to day 14 (defined as the number of days alive and free of renal replacement therapy from the last receipt of renal replacement therapy after enrollment to study day 14)
Measured: 14 days
Highest Stage of Acute Kidney Injury
Highest stage of acute kidney injury as defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria Stage 0 (no acute kidney injury) Stage 1 Serum creatinine 1.5-1.9 times baseline or ≥0.3 mg/dl (≥26.5 mmol/l) increase or Urine output <0.5 ml/kg/h for 6-12 hours Stage 2 Serum creatinine 2.0-2.9 times baseline or <0.5 ml/kg/h for ≥12 hours Stage 3 Serum creatinine 3.0 times baseline or Increase in serum creatinine to ≥4.0 mg/dl (≥353.6 mmol/l) or Initiation of renal replacement therapy or in patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m² or Urine output <0.3 ml/kg/h for ≥24 hours or anuria for ≥12 hours
Measured: 28 days
Highest Plasma Creatinine Between Enrollment and 28 Days After Enrollment
Highest plasma creatinine (mg/dL) between enrollment and 28 days after enrollment, censored at hospital discharge
Measured: 28 days
Receipt of Renal Replacement Therapy
receipt of renal replacement therapy between enrollment and the first of 28 days or hospital discharge
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 posted9 Jun 2014 (estimated)
- Study startJul 2014
- Primary completionFeb 2016
- Study completionApr 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 (1)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
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew Semler, Vanderbilt University
- Investigators
- Matthew W. Semler, M.D., Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02159079
- Sponsor's protocol ID
- 140582
- Acronym
- BALANCE
- Status last verified
- Oct 2019
- First submitted
- 3 Jun 2014
- Last updated
- 1 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Semler MW, Janz DR, Casey JD, Self WH, Rice TW. Conservative Fluid Management After Sepsis Resuscitation: A Pilot Randomized Trial. J Intensive Care Med. 2020 Dec;35(12):1374-1382. doi: 10.1177/0885066618823183. Epub 2019 Jan 10.
PubMed 30630380
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction
- ClinicalTrials.gov ID
- NCT02159079
- Acronym / sponsor ID
- BALANCE / 140582
- Conditions
- Sepsis
- Keywords
- Sepsis, Severe Sepsis, Septic Shock, Conservative Fluid Management, Fluid Balance, Fluid Restriction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 9 Jun 2014 (estimated)
- Results
- Posted 1 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sepsis is a common inflammatory response to infection characterized by hypovolemia and vasodilation for which early administration of intravenous fluids has been suggested to improve outcomes. The ideal fluid balance following initial resuscitation is unclear. Septic patients treated in the intensive care unit commonly receive significant volumes of intravenous fluids with resultant positive fluid balance for up to a week after their initial resuscitation. Observational studies have associated fluid receipt and positive fluid balance in patients with severe sepsis and septic shock with increased mortality but are inherently limited by indication bias. In order to determine the optimal approach to fluid management following resuscitation in patients with severe sepsis and septic shock, a randomized controlled trial is needed. The primary hypothesis of this study is that, compared to usual care, a conservative approach to fluid management after resuscitation in patients with sepsis and cardiopulmonary dysfunction will increase intensive care unit free days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Usual Care | No intervention | –Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel. |
| Conservative Fluid Management Strategy | Experimental | Other: Conservative Fluid Management StrategyFor patients in the conservative fluid management arm, beginning 12 hours after admission to study ICU and ending at the first of ICU discharge, death, return to home inspired oxygen, or study day 14, fluid management will be controlled by a study protocol. Patients in shock will receive fluid boluses only as specified by the protocol for oliguria and rapidly increasing vasopressor requirement. Patients not in shock will receive fluid boluses only as specified by the protocol for oliguria. Output will exceed input each day using a diuretic drip if required. Study protocol will be held only for pre-specified Safety Endpoints of persistent oliguria, decompensating shock, diuretic side effect, and intervening acute event. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ICU patients
- Adults
- Sepsis as defined by at least two systemic inflammatory response syndrome criteria and receipt of antimicrobial therapy
- Cardiopulmonary dysfunction as defined shock or respiratory failure
Key exclusion criteria (22 listed)
- Inability to obtain consent
- Greater than 48 hours since inclusion criteria initially met
- Allergy to furosemide AND bumetanide
- Rhabdomyolysis with creatinine kinase > 5000 U/L
- Hypercalcemia with calcium >11 mg/dL
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 |
|---|---|---|
| Conservative Fluid Management StrategyFor patients in the conservative fluid management arm, beginning 12 hours after admission to study ICU and ending at the first of ICU discharge, death, return to home inspired oxygen, or study day 14, fluid management will be controlled by a study protocol. Patients in shock will receive fluid boluses only as specified by the protocol for oliguria and rapidly increasing vasopressor requirement. Patients not in shock will receive fluid boluses only as specified by the protocol for oliguria. Output will exceed input each day using a diuretic drip if required. Study protocol will be held only for pre-specified Safety Endpoints of persistent oliguria, decompensating shock, diuretic side effect, and intervening acute event. | Other | Conservative Fluid Management Strategy |
Primary outcome
ICU-free Days to 14 Days After Enrollment
Time frame: 14 days
The primary outcome will be the number of ICU-free days to day 14 (defined as the number days alive and outside of the intensive care unit in the first 14 days after enrollment).
6 secondary outcomes
Ventilator-free Days to Day 14
Time frame: 14 days
In-hospital Mortality to Day 14
Time frame: 14 days
Renal Replacement Therapy-free Days to Day 14
Time frame: 14 days
Highest Stage of Acute Kidney Injury
Time frame: 28 days
Highest Plasma Creatinine Between Enrollment and 28 Days After Enrollment
Time frame: 28 days
Receipt of Renal Replacement Therapy
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30630380Semler MW, Janz DR, Casey JD, Self WH, Rice TW. Conservative Fluid Management After Sepsis Resuscitation: A Pilot Randomized Trial. J Intensive Care Med. 2020 Dec;35(12):1374-1382. doi: 10.1177/0885066618823183. Epub 2019 Jan 10.
Related trials for Sepsis
Not yet recruiting
Metabolic Profiling Among Patients Suspected of Infective Endocarditis - PPSIE Comparing Metabolomes of Bloodstream Infections Versus Infective Endocarditis
Infective Endocarditis (IE)
Active, not recruiting
Compassionate-Use of 4% T-EDTA Lock Solution for Central Venous Lines of Pediatric PN Patients
Central Line Complication, Central Line-associated Bloodstream Infection (CLABSI)
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Early Detection and Kinetics of Sepsis-Induced Coagulopathy in Severe Burn Patients
Sepsis, Sepsis-induced Coagulopathy
RecruitingPhase 3
THE ROLE OF PANCREATIC STONE PROTEIN (PSP) AND PSP-GUIDED EARLY MEROPENEM TREATMENT TO MITIGATE SEPSIS RISK AT THE EMERGENCY DEPARTMENT: THE PROMISE DOUBLE BLIND, PHASE III, RANDOMIZED CONTROLLED CLINICAL TRIAL
Sepsis
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.
Matthew W. Semler, M.D. principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Conservative Fluid Management Strategy in people with Sepsis, run by Vanderbilt University at 1 site 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 4 inclusion and 22 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 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 Nov 2019). 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?
ICU-free Days to 14 Days After Enrollment (time frame: 14 days). 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 NCT02159079, which also lists 1 linked publication.
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 1 Nov 2019.