Clinical trial NCT02159079: A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study)
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
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: Sepsis
Severe Sepsis
Septic Shock
Conservative Fluid Management
Fluid Balance
Fluid Restriction
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2014-06-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: ICU-free Days to 14 Days After Enrollment
timeFrame: 14 days
Secondary outcomes:
measure: Ventilator-free Days to Day 14
timeFrame: 14 days
measure: In-hospital Mortality to Day 14
timeFrame: 14 days
measure: Renal Replacement Therapy-free Days to Day 14
timeFrame: 14 days
measure: Highest Stage of Acute Kidney Injury
timeFrame: 28 days
measure: Highest Plasma Creatinine Between Enrollment and 28 Days After Enrollment
timeFrame: 28 days
measure: Receipt of Renal Replacement Therapy
timeFrame: 28 days
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Matthew W. Semler, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.