Trial Outcomes & Findings for A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study) (NCT NCT02159079)

NCT ID: NCT02159079

Last Updated: 2019-11-01

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 30 participants
• Primary outcome timeframe: 14 days
• Results posted on: 2019-11-01

Participant Flow

Participant milestones

Measure	Usual Care Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy 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.
Overall Study STARTED	15	15
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Controlled Trial of a Conservative Fluid Balance Strategy for Patients With Sepsis and Cardiopulmonary Dysfunction (BALANCE Study)

Baseline characteristics by cohort

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	61 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.
ICU-free Days to 14 Days After Enrollment	9 days Interval 0.0 to 12.0	11 days Interval 0.0 to 12.0

SECONDARY outcome

Timeframe: 14 days

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)

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.
Ventilator-free Days to Day 14	13 days Interval 0.0 to 14.0	12 days Interval 0.0 to 14.0

SECONDARY outcome

Timeframe: 14 days

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).

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.
In-hospital Mortality to Day 14	4 Participants	3 Participants

SECONDARY outcome

Timeframe: 14 days

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)

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.
Renal Replacement Therapy-free Days to Day 14	14 days Interval 0.0 to 14.0	14 days Interval 14.0 to 14.0

SECONDARY outcome

Timeframe: 28 days

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

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=14 Participants 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.
Highest Stage of Acute Kidney Injury No acute kidney injury	5 Participants	6 Participants
Highest Stage of Acute Kidney Injury Stage I	0 Participants	2 Participants
Highest Stage of Acute Kidney Injury Stage II	4 Participants	3 Participants
Highest Stage of Acute Kidney Injury Stage III	6 Participants	3 Participants

SECONDARY outcome

Timeframe: 28 days

Highest plasma creatinine (mg/dL) between enrollment and 28 days after enrollment, censored at hospital discharge

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.
Highest Plasma Creatinine Between Enrollment and 28 Days After Enrollment	2.3 mg/dL Interval 1.1 to 3.1	1.3 mg/dL Interval 0.8 to 2.1

SECONDARY outcome

Timeframe: 28 days

receipt of renal replacement therapy between enrollment and the first of 28 days or hospital discharge

Outcome measures

Measure	Usual Care n=15 Participants Patients in the usual care arm will be managed exclusively by their treating clinician without input from study personnel.	Conservative Fluid Management Strategy n=15 Participants 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.
Receipt of Renal Replacement Therapy	1 Participants	1 Participants

Adverse Events

Usual Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 4 deaths

Conservative Fluid Management Strategy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Matthew W. Semler, MD, MSc

VANDERBILT UNIVERSITY MEDICAL CENTER

Phone: (615) 322-3412

Email: matthew.w.semler@vumc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place