Back to resultsA Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study) (BALANCE)
Primary Purpose
Sepsis
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Conservative Fluid Management Strategy
Sponsored by
About this trial
This is an interventional treatment trial for Sepsis focused on measuring Sepsis, Severe Sepsis, Septic Shock, Conservative Fluid Management, Fluid Balance, Fluid Restriction
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Usual Care
Conservative Fluid Management Strategy
Arm Description
Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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)
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).
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)
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
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
Receipt of Renal Replacement Therapy
receipt of renal replacement therapy between enrollment and the first of 28 days or hospital discharge
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02159079
Brief Title
A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study)
Acronym
BALANCE
Official Title
A Phase II/III Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
Sepsis, Severe Sepsis, Septic Shock, Conservative Fluid Management, Fluid Balance, Fluid Restriction
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Usual Care
Arm Type
No Intervention
Arm Description
Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.
Arm Title
Conservative Fluid Management Strategy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Conservative Fluid Management Strategy
Intervention Description
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.
Primary Outcome Measure Information:
Title
ICU-free Days to 14 Days After Enrollment
Description
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).
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Ventilator-free Days to Day 14
Description
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)
Time Frame
14 days
Title
In-hospital Mortality to Day 14
Description
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).
Time Frame
14 days
Title
Renal Replacement Therapy-free Days to Day 14
Description
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)
Time Frame
14 days
Title
Highest Stage of Acute Kidney Injury
Description
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
Time Frame
28 days
Title
Highest Plasma Creatinine Between Enrollment and 28 Days After Enrollment
Description
Highest plasma creatinine (mg/dL) between enrollment and 28 days after enrollment, censored at hospital discharge
Time Frame
28 days
Title
Receipt of Renal Replacement Therapy
Description
receipt of renal replacement therapy between enrollment and the first of 28 days or hospital discharge
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew W. Semler, M.D.
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30630380
Citation
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.
Results Reference
derived
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A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study)
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