Trial Outcomes & Findings for Isotonic Solution Administration Logistical Testing (NCT NCT02345486)

Results Overview

Proportion of total intravenous isotonic crystalloid administered during admission to the intensive care unit that is 0.9% sodium chloride, censored at 30 days. The primary outcome was the proportion of intravenous isotonic crystalloid administered in the ICU that was saline. This was a continuous variable calculated for each patient as the volume of saline received divided by volume of saline received plus volume of balanced crystalloids received with a range from 0.0 (no saline received) to 1.0 (only saline received).

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

974 participants

Primary outcome timeframe

30 days

Results posted on

2019-11-13

Participant Flow

This cluster-randomized, multiple-crossover trial enrolled 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015.

Participant milestones

Participant milestones
Measure	0.9% Sodium Chloride Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Overall Study STARTED	454	520
Overall Study COMPLETED	454	520
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Isotonic Solution Administration Logistical Testing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid	Total n=974 Participants Total of all reporting groups
Age, Continuous	58 years n=5 Participants	57 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	208 Participants n=5 Participants	252 Participants n=7 Participants	460 Participants n=5 Participants
Sex: Female, Male Male	246 Participants n=5 Participants	268 Participants n=7 Participants	514 Participants n=5 Participants
Region of Enrollment United States	454 participants n=5 Participants	520 participants n=7 Participants	974 participants n=5 Participants
Body mass index	26.4 kg/m^2 n=5 Participants	26.7 kg/m^2 n=7 Participants	26.6 kg/m^2 n=5 Participants
Chronic kidney disease, stage III or greater	104 Participants n=5 Participants	119 Participants n=7 Participants	223 Participants n=5 Participants
Previous renal replacement therapy	44 Participants n=5 Participants	42 Participants n=7 Participants	86 Participants n=5 Participants
Source of ICU Admission Emergency Department	256 Participants n=5 Participants	310 Participants n=7 Participants	566 Participants n=5 Participants
Source of ICU Admission Transfer from another hospital	93 Participants n=5 Participants	106 Participants n=7 Participants	199 Participants n=5 Participants
Source of ICU Admission Hospital ward	80 Participants n=5 Participants	79 Participants n=7 Participants	159 Participants n=5 Participants
Source of ICU Admission Another ICU within the hospital	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Source of ICU Admission Operating room	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Source of ICU Admission Outpatient	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Mechanical ventilation	155 Participants n=5 Participants	174 Participants n=7 Participants	329 Participants n=5 Participants
Vasopressors	111 Participants n=5 Participants	114 Participants n=7 Participants	225 Participants n=5 Participants
Acute kidney injury, stage II or greater	87 Participants n=5 Participants	96 Participants n=7 Participants	183 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days

Proportion of total intravenous isotonic crystalloid administered during admission to the intensive care unit that is 0.9% sodium chloride, censored at 30 days. The primary outcome was the proportion of intravenous isotonic crystalloid administered in the ICU that was saline. This was a continuous variable calculated for each patient as the volume of saline received divided by volume of saline received plus volume of balanced crystalloids received with a range from 0.0 (no saline received) to 1.0 (only saline received).

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Proportion of Isotonic Crystalloid Which is 0.9% Saline	91.2 Percentage of fluid that was saline Interval 0.0 to 100.0	21.0 Percentage of fluid that was saline Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: 30 days

Proportion of total intravenous isotonic crystalloid administered during admission to the intensive care unit that is either Lactated ringers or Plasmalyte-A, censored at 30 days.

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Proportion of Isotonic Crystalloid Which is Physiologically Balanced	8.8 Percentage of fluid that was balanced Interval 0.0 to 100.0	78.8 Percentage of fluid that was balanced Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: 30 days

Total volume of intravenous fluid administration during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Total Intravenous Input	2000 milliliters Interval 792.0 to 4630.0	2125 milliliters Interval 1000.0 to 4625.0

SECONDARY outcome

Timeframe: 30 days

Total volume of intravenous isotonic crystalloid administration during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Total Isotonic Crystalloid Input	1424 mL Interval 500.0 to 3377.0	1617 mL Interval 500.0 to 3628.0

SECONDARY outcome

Timeframe: 30 days

Total volume of intravenous colloid administration (excluding blood products) during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Total Intravenous Colloid Input	0 milliliters Interval 0.0 to 0.0	0 milliliters Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 30 days

Total volume of packed red blood cells, platelets, and fresh frozen plasma administered during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Total Intravenous Blood Product Administration	0 milliliters Interval 0.0 to 0.0	0 milliliters Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 30 days

highest serum chloride (mmol/L) during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Highest Serum Chloride Between Enrollment and Day 30	109 mmol/L Interval 105.0 to 113.0	108 mmol/L Interval 104.0 to 112.0

SECONDARY outcome

Timeframe: 30 days

Highest serum sodium concentration (mmol/L) during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Highest Serum Sodium Between Enrollment and Day 30	141 mmol/L Interval 139.0 to 144.0	141 mmol/L Interval 138.0 to 144.0

SECONDARY outcome

Timeframe: 30 days

Lowest serum bicarbonate concentration (mmol/L) during admission to the intensive care unit, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Lowest Bicarbonate Concentration Between Enrollment and Day 30	19 mmol/L Interval 16.0 to 22.0	19 mmol/L Interval 15.0 to 22.0

SECONDARY outcome

Timeframe: 30 days

Incidence of Major Adverse Kidney Events by 30 days -- a composite outcome defined as one or more of the following: death, new use of renal replacement therapy, or persistence of renal dysfunction at hospital discharge or at 30 days (defined as an increase in serum creatinine ≥ 200% from baseline)

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Number of Patients With MAKE30	112 Participants	128 Participants

SECONDARY outcome

Timeframe: 30 days

Death prior to the earlier of hospital discharge or day 30

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
In-hospital Mortality	68 Participants	72 Participants

SECONDARY outcome

Timeframe: 30 days

Receipt of new renal replacement therapy after the first study day, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
New Use of Renal Replacement Therapy	14 Participants	24 Participants

SECONDARY outcome

Timeframe: 30 days

Persistence of renal dysfunction at hospital discharge or at 30 days (defined as an increase in serum creatinine ≥ 200% from baseline)

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Persistent Renal Dysfunction	59 Participants	76 Participants

SECONDARY outcome

Timeframe: 30 days

Population: Order for intravenous crystalloid is the unit analyzed; each patient could have multiple orders for intravenous crystalloid

Number of contraindications to assigned study fluid identified by providers, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=588 Orders for intravenous crystalloid Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=854 Orders for intravenous crystalloid Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Number of Contraindications	28 Orders for intravenous crystalloid	66 Orders for intravenous crystalloid

SECONDARY outcome

Timeframe: 30 days

Incidence of hyperchloremia defined as a serum chloride greater than or equal to 110 mmol/L

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Incidence of Hyperchloremia	171 Participants	171 Participants

SECONDARY outcome

Timeframe: 30 days

Incidence of severe hypochloremia defined as a serum chloride less than 90mmol/L

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Incidence of Severe Hypochloremia	34 Participants	32 Participants

SECONDARY outcome

Timeframe: 30 days

Increase in serum creatinine during hospitalization, censored at 30 days Change from baseline to highest value, median (IQR), mg/dl

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Increase in Serum Creatinine	0.07 mg/dL Interval -0.1 to 0.5	0.07 mg/dL Interval -0.1 to 0.5

SECONDARY outcome

Timeframe: 30 days

Incidence of stage II or III acute kidney injury by Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury criteria, censored at 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Incidence of Acute Kidney Injury	129 Participants	135 Participants

SECONDARY outcome

Timeframe: 28 days

ICU-free days to 28 days after enrollment will be defined as the number of days alive and not admitted to an intensive care unit service after the patient's final discharge from the intensive care unit before 28 days. If the patient is admitted to an intensive care unit service at day 28 or dies prior to day 28, ICU-free days will be 0.

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Intensive Care Unit Free Days to Day 28	25.1 days Interval 22.1 to 26.2	25.2 days Interval 21.8 to 26.4

SECONDARY outcome

Timeframe: 28 days

Ventilator-free days to day 28 will be defined as the number of days alive and with unassisted breathing to day 28 after enrollment, assuming a patient survives for at least two consecutive calendar days after initiating unassisted breathing and remains free of assisted breathing. If a patient returns to assisted breathing and subsequently achieves unassisted breathing prior to day 28, VFD will be counted from the end of the last period of assisted breathing to day 28. If the patient is receiving assisted ventilation at day 28 or dies prior to day 28, VFD will be 0.

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Ventilator-free Days (VFD) to Day 28	28.0 days Interval 27.0 to 28.0	28.0 days Interval 26.0 to 28.0

SECONDARY outcome

Timeframe: 28 days

Dialysis free survival to day 28 will be defined as the number of days alive and without dialysis receipt to day 28 after enrollment, assuming a patient survives for at least two consecutive calendar days after last receipt of dialysis and remains free of dialysis. If the patient is receiving dialysis at day 28 or dies prior to day 28, VFD will be 0.

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Dialysis-free Survival to Day 28	28.0 days Interval 28.0 to 28.0	28.0 days Interval 28.0 to 28.0

SECONDARY outcome

Timeframe: 30 days

Highest creatinine value in the first 30 days

Outcome measures

Outcome measures
Measure	0.9% Sodium Chloride n=454 Participants Participants in the '0.9% sodium chloride' arm will receive 0.9% sodium chloride ('normal saline') any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. 0.9% sodium chloride	Physiologically Balanced Fluid n=520 Participants Participants in the 'physiologically balanced fluid' arm will receive physiologically balanced fluid (Lactated ringers or Plasmalyte-A) any time an isotonic crystalloid is ordered by a provider during the intensive care unit admission. Physiologically balanced fluid
Peak Creatinine in the First 30 Days	1.19 mg/dL Interval 0.81 to 2.3	1.19 mg/dL Interval 0.8 to 2.62

Adverse Events

0.9% Sodium Chloride

Serious events: 0 serious events

Other events: 0 other events

Deaths: 68 deaths

Physiologically Balanced Fluid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 72 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Matthew Semler

Vanderbilt University Medical Center

Phone: 615-322-3412

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place