Trial Outcomes & Findings for Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: A Pilot Feasibility Study (NCT NCT03340805)
NCT ID: NCT03340805
Last Updated: 2019-08-05
Results Overview
Proportion of total crystalloids administered as saline in each arm during the intervention phase
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
50 participants
Primary outcome timeframe
up 48 hours after randomization
Results posted on
2019-08-05
Participant Flow
Participant milestones
| Measure |
Lactated Ringer's Fluid (LR)
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
26
|
|
Overall Study
COMPLETED
|
24
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: A Pilot Feasibility Study
Baseline characteristics by cohort
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
24 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
50 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
3.8 years
n=93 Participants
|
9.7 years
n=4 Participants
|
5.8 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Non-Hispanic White
|
11 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Non-Hispanic Black
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Hispanic
|
10 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Asian
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Unknown/Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=93 Participants
|
26 participants
n=4 Participants
|
50 participants
n=27 Participants
|
|
Comorbid Conditions
Cancer
|
4 participants
n=93 Participants
|
5 participants
n=4 Participants
|
9 participants
n=27 Participants
|
|
Comorbid Conditions
Kidney disease
|
2 participants
n=93 Participants
|
1 participants
n=4 Participants
|
3 participants
n=27 Participants
|
|
Comorbid Conditions
Neurologic dysfunction
|
7 participants
n=93 Participants
|
5 participants
n=4 Participants
|
12 participants
n=27 Participants
|
|
Comorbid Conditions
Chronic ventilator dependence
|
6 participants
n=93 Participants
|
5 participants
n=4 Participants
|
11 participants
n=27 Participants
|
|
Comorbid Conditions
Bone marrow or solid organ transplant
|
3 participants
n=93 Participants
|
2 participants
n=4 Participants
|
5 participants
n=27 Participants
|
|
Comorbid Conditions
Sickle cell disease
|
0 participants
n=93 Participants
|
2 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Comorbid Conditions
Indwelling central venous catheter
|
6 participants
n=93 Participants
|
4 participants
n=4 Participants
|
10 participants
n=27 Participants
|
|
Comorbid Conditions
Any comorbid condition
|
16 participants
n=93 Participants
|
16 participants
n=4 Participants
|
32 participants
n=27 Participants
|
|
Site of Infection
Bacteremia
|
2 participants
n=93 Participants
|
4 participants
n=4 Participants
|
6 participants
n=27 Participants
|
|
Site of Infection
Pneumonia/lung infection
|
5 participants
n=93 Participants
|
5 participants
n=4 Participants
|
10 participants
n=27 Participants
|
|
Site of Infection
Abdominal infection
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Site of Infection
Urinary Tract Infection
|
4 participants
n=93 Participants
|
3 participants
n=4 Participants
|
7 participants
n=27 Participants
|
|
Site of Infection
CNS infection
|
2 participants
n=93 Participants
|
3 participants
n=4 Participants
|
5 participants
n=27 Participants
|
|
Site of Infection
Skin/soft tissue infection
|
2 participants
n=93 Participants
|
3 participants
n=4 Participants
|
5 participants
n=27 Participants
|
|
Site of Infection
Other
|
6 participants
n=93 Participants
|
6 participants
n=4 Participants
|
12 participants
n=27 Participants
|
|
Site of Infection
Unknown
|
3 participants
n=93 Participants
|
4 participants
n=4 Participants
|
7 participants
n=27 Participants
|
|
Site of Infection
Alternative diagnosis other than infection
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: up 48 hours after randomizationProportion of total crystalloids administered as saline in each arm during the intervention phase
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Compliance With Study Fluid Administration in the Assigned Study Arm
|
0 Proportion of total crystalloids adminis
Interval 0.0 to 0.0
|
100 Proportion of total crystalloids adminis
Interval 100.0 to 100.0
|
SECONDARY outcome
Timeframe: up to 6 monthsProportion of eligible patients treated in the pediatric ED who are enrolled, randomized, and treated with study fluid
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=59 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Enrollment of Eligible Patients
|
50 Participants
|
—
|
SECONDARY outcome
Timeframe: up to 6 monthsProportion of eligible patients who meet criteria for EFIC who are enrolled, randomized, and treated with study fluid and do not withdraw prior to completion of the follow-up phase
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=44 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Acceptability of Enrollment Using "Exception From Informed Consent"
|
43 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 90 days following randomizationProportion of enrolled patients who do not survive
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Mortality
|
0 Participants
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 28 days following randomizationThe number of calendar days alive and out of the hospital between randomization (day 0) and day 27 with death prior hospital discharge defined as "zero" hospital-free days
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Hospital-free Days
|
23 days alive and free of hospitalization
Interval 20.0 to 25.0
|
25 days alive and free of hospitalization
Interval 20.0 to 26.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 90 days following randomizationProportion treated with any replacement therapy that was not a continuation of pre-hospital chronic therapy
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
New Inpatient Dialysis
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 90 days following randomizationMeasured as the number of calendar days between ED arrival and ED or hospital discharge (whichever occurs later)
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Hospital Length of Stay
|
5 days
Interval 3.0 to 8.0
|
3 days
Interval 2.0 to 9.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to four days post-randomizationHyperlactatemia, hyperkalemia, hypercalcemia, hypernatremia, hyponatremia, hyperchloremia, therapy for brain herniation
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Adverse Events
|
7 adverse events
|
18 adverse events
|
OTHER_PRE_SPECIFIED outcome
Timeframe: up to seven days post-randomizationVenous thromboembolism
Outcome measures
| Measure |
Lactated Ringer's Fluid (LR)
n=24 Participants
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 Participants
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Adverse Events
|
0 Participants
|
0 Participants
|
Adverse Events
Lactated Ringer's Fluid (LR)
Serious events: 4 serious events
Other events: 11 other events
Deaths: 0 deaths
0.9% "Normal" Saline Fluid (NS)
Serious events: 2 serious events
Other events: 12 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Lactated Ringer's Fluid (LR)
n=24 participants at risk
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 participants at risk
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Cardiac disorders
Shock
|
8.3%
2/24 • Number of events 2 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
7.7%
2/26 • Number of events 2 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
12.5%
3/24 • Number of events 3 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
3.8%
1/26 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
General disorders
Death
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
3.8%
1/26 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Nervous system disorders
Cerebral edema
|
4.2%
1/24 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
0.00%
0/26 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
Other adverse events
| Measure |
Lactated Ringer's Fluid (LR)
n=24 participants at risk
Lactated Ringer's (LR) fluid will be administered to patients randomized to the experimental arm. LR will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Lactated Ringer: LR is a sterile, nonpyrogenic "balanced" solution used for fluid and electrolyte replenishment via intravenous or intraosseous administration. Each 100 mL of LR contains 600 mg sodium chloride (NaCl), 310 mg of sodium lactate (C3H5NaO3), 30 mg of potassium chloride (KCl), and 20 mg of calcium chloride (CaCl2 · 2H20) with an approximate potential of hydrogen (pH) of 6.5 (6.0 to 7.5).
|
0.9% "Normal" Saline Fluid (NS)
n=26 participants at risk
0.9% "normal" saline (NS) fluid will be administered to patients randomized to the active comparator (control) arm. NS will be used for all fluid boluses and maintenance fluids (supplemental electrolytes are allowed) from time immediately after randomization through 11:59 pm of the next calender day. The determination of when to give fluid, how much fluid to give, how fast to give fluid, and what access to use to administer fluid will remain at the discretion of the treating team.
Normal saline: Normal saline solution is an "unbalanced" crystalloid solution containing 154 mEq/L of sodium and 154 milliequivalent (mEq/L) of chloride.
|
|---|---|---|
|
Metabolism and nutrition disorders
Hyperlactatemia
|
8.3%
2/24 • Number of events 2 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
15.4%
4/26 • Number of events 4 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
8.3%
2/24 • Number of events 2 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
7.7%
2/26 • Number of events 2 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
15.4%
4/26 • Number of events 4 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Metabolism and nutrition disorders
Hypernatremia
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
0.00%
0/26 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
0.00%
0/26 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Metabolism and nutrition disorders
Hyperchloremia
|
12.5%
3/24 • Number of events 3 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
26.9%
7/26 • Number of events 7 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Vascular disorders
Thrombosis
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
0.00%
0/26 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
29.2%
7/24 • Number of events 7 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
23.1%
6/26 • Number of events 6 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Nervous system disorders
Seizure
|
4.2%
1/24 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
7.7%
2/26 • Number of events 2 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
3.8%
1/26 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
4/24 • Number of events 4 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
15.4%
4/26 • Number of events 4 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Hepatobiliary disorders
Liver dysfunction
|
0.00%
0/24 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
3.8%
1/26 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
|
Skin and subcutaneous tissue disorders
Pressure injury
|
4.2%
1/24 • Number of events 1 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
0.00%
0/26 • 7 days
Selective AEs recorded were: Death, Cardiac arrest, Arrhythmia requiring intervention, Vasoactive infusion, ECMO, Invasive mechanical ventilation, Non-invasive mechanical ventilation, Dialysis (not pre-existing), Liver dysfunction, Limb necrosis, Brain herniation, Seizure, Pulmonary embolus, Deep venous thrombosis, Central venous line clot requiring pharmacologic therapy, Bleeding, Hospital infection, Pressure ulcer, IV infiltrate (grade 3 or 4), Rash, and electrolyte abnormalities
|
Additional Information
Dr. Scott L. Weiss, study co-PI
The Children's Hospital of Philadelphia
Phone: 215-590-5505
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place