Trial Outcomes & Findings for Pain Reduction With Intranasal Medications for Extremity Injuries (NCT NCT02778880)
NCT ID: NCT02778880
Last Updated: 2020-09-01
Results Overview
A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
90 participants
Primary outcome timeframe
30 minutes after study medication
Results posted on
2020-09-01
Participant Flow
This clinical trial took place at a tertiary care children's hospital emergency department from March 2016 to February 2017. The study sample was identified through an established triage process identifying children with an acute painful extremity injury. These patients were ages 8-17 years with a visual analog scale (VAS) score greater than 35 mm.
Participant milestones
| Measure |
Ketamine
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Overall Study
STARTED
|
45
|
45
|
|
Overall Study
COMPLETED
|
44
|
42
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
One patient in the Ketamine group did not have a baseline pain score documented.
Baseline characteristics by cohort
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
11.8 years
STANDARD_DEVIATION 2.6 • n=44 Participants
|
12.2 years
STANDARD_DEVIATION 2.3 • n=42 Participants
|
12.0 years
STANDARD_DEVIATION 2.5 • n=86 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=44 Participants
|
11 Participants
n=42 Participants
|
29 Participants
n=86 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=44 Participants
|
31 Participants
n=42 Participants
|
57 Participants
n=86 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · White
|
30 Participants
n=44 Participants
|
29 Participants
n=42 Participants
|
59 Participants
n=86 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Black
|
11 Participants
n=44 Participants
|
10 Participants
n=42 Participants
|
21 Participants
n=86 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Hispanic
|
0 Participants
n=44 Participants
|
2 Participants
n=42 Participants
|
2 Participants
n=86 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Other
|
3 Participants
n=44 Participants
|
1 Participants
n=42 Participants
|
4 Participants
n=86 Participants
|
|
Weight
|
45.8 kilograms
STANDARD_DEVIATION 14.4 • n=44 Participants
|
50.8 kilograms
STANDARD_DEVIATION 22.8 • n=42 Participants
|
48.3 kilograms
STANDARD_DEVIATION 18.6 • n=86 Participants
|
|
Mechanism of Injury
Sports Related/Recreational
|
30 Participants
n=44 Participants
|
26 Participants
n=42 Participants
|
56 Participants
n=86 Participants
|
|
Mechanism of Injury
Motor Vehicle Accident
|
1 Participants
n=44 Participants
|
2 Participants
n=42 Participants
|
3 Participants
n=86 Participants
|
|
Mechanism of Injury
Fall
|
10 Participants
n=44 Participants
|
13 Participants
n=42 Participants
|
23 Participants
n=86 Participants
|
|
Mechanism of Injury
Other
|
3 Participants
n=44 Participants
|
1 Participants
n=42 Participants
|
4 Participants
n=86 Participants
|
|
Time of injury prior to arrival
|
43.0 minutes
n=44 Participants
|
51.5 minutes
n=42 Participants
|
47.3 minutes
n=86 Participants
|
|
Extremity
Upper Extremity
|
33 participants
n=44 Participants
|
28 participants
n=42 Participants
|
61 participants
n=86 Participants
|
|
Extremity
Lower Extremity
|
13 participants
n=44 Participants
|
15 participants
n=42 Participants
|
28 participants
n=86 Participants
|
|
Diagnosis
Fracture
|
39 participants
n=44 Participants
|
34 participants
n=42 Participants
|
73 participants
n=86 Participants
|
|
Diagnosis
Dislocation
|
4 participants
n=44 Participants
|
2 participants
n=42 Participants
|
6 participants
n=86 Participants
|
|
Diagnosis
Sprain/Strain
|
1 participants
n=44 Participants
|
5 participants
n=42 Participants
|
6 participants
n=86 Participants
|
|
Diagnosis
Other
|
2 participants
n=44 Participants
|
1 participants
n=42 Participants
|
3 participants
n=86 Participants
|
|
Reduction Required
|
19 Participants
n=44 Participants
|
23 Participants
n=42 Participants
|
42 Participants
n=86 Participants
|
|
Sedation Required
|
19 Participants
n=44 Participants
|
20 Participants
n=42 Participants
|
39 Participants
n=86 Participants
|
|
Analgesic Prior to Arrival
Ibuprofen
|
4 Participants
n=44 Participants
|
4 Participants
n=42 Participants
|
8 Participants
n=86 Participants
|
|
Analgesic Prior to Arrival
Acetaminophen
|
1 Participants
n=44 Participants
|
2 Participants
n=42 Participants
|
3 Participants
n=86 Participants
|
|
Analgesic Prior to Arrival
Naproxen
|
0 Participants
n=44 Participants
|
1 Participants
n=42 Participants
|
1 Participants
n=86 Participants
|
|
Analgesic Prior to Arrival
No Analgesic
|
39 Participants
n=44 Participants
|
35 Participants
n=42 Participants
|
74 Participants
n=86 Participants
|
|
Initial VAS score
|
74.7 score on a scale
STANDARD_DEVIATION 15.3 • n=43 Participants • One patient in the Ketamine group did not have a baseline pain score documented.
|
72.0 score on a scale
STANDARD_DEVIATION 18.6 • n=42 Participants • One patient in the Ketamine group did not have a baseline pain score documented.
|
73.4 score on a scale
STANDARD_DEVIATION 17.0 • n=85 Participants • One patient in the Ketamine group did not have a baseline pain score documented.
|
|
Baseline Heart Rate
|
90.8 beats per minute
STANDARD_DEVIATION 15.2 • n=44 Participants
|
88.6 beats per minute
STANDARD_DEVIATION 14.8 • n=42 Participants
|
89.7 beats per minute
STANDARD_DEVIATION 15.0 • n=86 Participants
|
|
Baseline Respiratory Rate
|
22.1 breaths per minute
STANDARD_DEVIATION 6.6 • n=44 Participants
|
23.0 breaths per minute
STANDARD_DEVIATION 7.4 • n=42 Participants
|
22.5 breaths per minute
STANDARD_DEVIATION 7.0 • n=86 Participants
|
|
Baseline Systolic Blood Pressure
|
126.5 mmHg
STANDARD_DEVIATION 19.1 • n=44 Participants
|
128.9 mmHg
STANDARD_DEVIATION 19.6 • n=42 Participants
|
127.7 mmHg
STANDARD_DEVIATION 19.4 • n=86 Participants
|
|
Baseline Diastolic Blood Pressure
|
78.9 mmHg
STANDARD_DEVIATION 13.6 • n=44 Participants
|
73.5 mmHg
STANDARD_DEVIATION 12.9 • n=42 Participants
|
76.3 mmHg
STANDARD_DEVIATION 13.5 • n=86 Participants
|
|
Baseline Oxygen Saturation
|
99.8 percent
STANDARD_DEVIATION 0.6 • n=44 Participants
|
99.6 percent
STANDARD_DEVIATION 0.6 • n=42 Participants
|
99.7 percent
STANDARD_DEVIATION 0.6 • n=86 Participants
|
|
Baseline End Tidal Captometry
|
36.6 mmHg
STANDARD_DEVIATION 6.4 • n=44 Participants
|
38.0 mmHg
STANDARD_DEVIATION 4.4 • n=42 Participants
|
37.3 mmHg
STANDARD_DEVIATION 5.5 • n=86 Participants
|
|
Time to Study Medication from Arrival
|
26.6 minutes
STANDARD_DEVIATION 9.9 • n=44 Participants
|
26.1 minutes
STANDARD_DEVIATION 10.3 • n=42 Participants
|
26.4 minutes
STANDARD_DEVIATION 10.1 • n=86 Participants
|
|
Volume of Study Medication Administered
|
1.3 milliliters
n=44 Participants
|
1.8 milliliters
n=42 Participants
|
1.6 milliliters
n=86 Participants
|
|
Dose of Study Medication Administered (Ketamine)
|
1.5 milligrams per kilogram (mg/kg)
n=44 Participants • Participants receiving Fentanyl did not receive Ketamine
|
—
|
1.5 milligrams per kilogram (mg/kg)
n=44 Participants • Participants receiving Fentanyl did not receive Ketamine
|
|
Dose of Study Medication Administered (Fentanyl)
|
—
|
1.9 micrograms per kilogram (mcg/kg)
n=42 Participants • Participants receiving Ketamine did not receive Fentanyl
|
1.9 micrograms per kilogram (mcg/kg)
n=42 Participants • Participants receiving Ketamine did not receive Fentanyl
|
PRIMARY outcome
Timeframe: 30 minutes after study medicationPopulation: One patient in the ketamine group did not have a baseline pain score documented and four patients withdrew from the study (1 in the ketamine group, 3 in the fentanyl group), resulting in 43 patients randomized to the ketamine group and 42 patients randomized to the fentanyl group included in the primary outcome analysis.
A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
Outcome measures
| Measure |
Ketamine
n=43 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Difference From Baseline in Visual Analog Scale Pain Score
|
-30.6 score on a scale
Interval -35.8 to -25.4
|
-31.9 score on a scale
Interval -37.2 to -26.6
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationPopulation: One patient in the ketamine group did not have a baseline pain score documented and four patients withdrew from the study (1 in the ketamine group, 3 in the fentanyl group), resulting in 43 patients randomized to the ketamine group and 42 patients randomized to the fentanyl group included in this secondary outcome analysis.
A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
Outcome measures
| Measure |
Ketamine
n=43 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Difference From Baseline in Visual Analog Scale Pain Score
|
-24.4 score on a scale
Interval -29.3 to -19.4
|
-25.3 score on a scale
Interval -30.3 to -20.3
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationPopulation: One patient in the ketamine group did not have a baseline pain score documented and four patients withdrew from the study (1 in the ketamine group, 3 in the fentanyl group), resulting in 43 patients randomized to the ketamine group and 42 patients randomized to the fentanyl group included in this secondary outcome analysis.
A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
Outcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Difference From Baseline in Visual Analog Scale Pain Score
|
-27.7 score on a scale
Interval -33.8 to -21.6
|
-29.0 score on a scale
Interval -35.1 to -22.8
|
SECONDARY outcome
Timeframe: 15, 30, and 60 minutes after study medication administrationThe University of Michigan Sedation Scale is a valid and reliable tool that allows for rapid assessment of the depth of sedation in children. It is a simple observational tool that assesses the level of alertness on a five-point scale. It has been validated in children and has shown to have significant inter-rater reliability. Score is 0-4 (0 = awake and alert; 1= minimally sedated; 2 = moderately sedated; 3 = deeply sedated; 4 = unarousable)
Outcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Highest Achieved University of Michigan Sedation Scale (UMSS) Score
UMSS 0
|
23 Participants
|
32 Participants
|
|
Highest Achieved University of Michigan Sedation Scale (UMSS) Score
UMSS 1
|
17 Participants
|
9 Participants
|
|
Highest Achieved University of Michigan Sedation Scale (UMSS) Score
UMSS 2
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Within the first 60 minutes after study medicationDocumentation of additional pain medication after study medication administration
Outcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Rescue Analgesia
Ibuprofen
|
1 Participants
|
3 Participants
|
|
Rescue Analgesia
Fentanyl
|
1 Participants
|
3 Participants
|
|
Rescue Analgesia
Morphine
|
7 Participants
|
3 Participants
|
|
Rescue Analgesia
Ketamine
|
1 Participants
|
0 Participants
|
|
Rescue Analgesia
Toradol
|
1 Participants
|
0 Participants
|
|
Rescue Analgesia
No rescue analgesia
|
33 Participants
|
33 Participants
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Heart Rate
|
90.1 beats per minute
Standard Deviation 12.8
|
84.4 beats per minute
Standard Deviation 14.1
|
SECONDARY outcome
Timeframe: 30 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Heart Rate
|
90.5 beats per minute
Standard Deviation 12.8
|
85.6 beats per minute
Standard Deviation 13.5
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Heart Rate
|
85.1 beats per minute
Standard Deviation 12.4
|
82.9 beats per minute
Standard Deviation 12.9
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Respiratory Rate
|
23.1 breaths per minute
Standard Deviation 11.9
|
22.3 breaths per minute
Standard Deviation 5.8
|
SECONDARY outcome
Timeframe: 30 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Respiratory Rate
|
23.3 breaths per minute
Standard Deviation 8.7
|
19.9 breaths per minute
Standard Deviation 5.7
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Respiratory Rate
|
21.8 breaths per minute
Standard Deviation 8.1
|
19.7 breaths per minute
Standard Deviation 5.7
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Systolic Blood Pressure
|
127.3 mmHg
Standard Deviation 18.0
|
127.9 mmHg
Standard Deviation 19.3
|
SECONDARY outcome
Timeframe: 30 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Systolic Blood Pressure
|
126.3 mmHg
Standard Deviation 15.0
|
123.4 mmHg
Standard Deviation 15.6
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Systolic Blood Pressure
|
122.3 mmHg
Standard Deviation 14.9
|
122.0 mmHg
Standard Deviation 15.1
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Diastolic Blood Pressure
|
76.1 mmHg
Standard Deviation 10.7
|
73.4 mmHg
Standard Deviation 12.7
|
SECONDARY outcome
Timeframe: 30 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Diastolic Blood Pressure
|
76.3 mmHg
Standard Deviation 10.3
|
73.6 mmHg
Standard Deviation 11.2
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Diastolic Blood Pressure
|
70.8 mmHg
Standard Deviation 9.2
|
70.6 mmHg
Standard Deviation 10.4
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Oxygen Saturation
|
99.6 percent
Standard Deviation 0.7
|
99.2 percent
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: 30 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Oxygen Saturation
|
99.5 percent
Standard Deviation 0.7
|
99.4 percent
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Oxygen Saturation
|
99.3 percent
Standard Deviation 0.9
|
99.3 percent
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: 15 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Capnometry Value
|
36.6 mmHg
Standard Deviation 5.2
|
38.3 mmHg
Standard Deviation 4.2
|
SECONDARY outcome
Timeframe: 30 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Capnometry Value
|
38.6 mmHg
Standard Deviation 5.6
|
40.4 mmHg
Standard Deviation 6.8
|
SECONDARY outcome
Timeframe: 60 minutes after study medicationOutcome measures
| Measure |
Ketamine
n=44 Participants
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 Participants
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Capnometry Value
|
38.7 mmHg
Standard Deviation 4.2
|
38.9 mmHg
Standard Deviation 5.4
|
Adverse Events
Ketamine
Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths
Fentanyl
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ketamine
n=44 participants at risk
Ketamine 1.5 mg/kg intranasally for one dose
|
Fentanyl
n=42 participants at risk
Fentanyl 2 mcg/kg intranasally for one dose
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
20.5%
9/44 • 30 days
|
16.7%
7/42 • 30 days
|
|
Nervous system disorders
Dysphoria/Dissociation
|
2.3%
1/44 • 30 days
|
0.00%
0/42 • 30 days
|
|
Gastrointestinal disorders
Unpleasant Taste
|
20.5%
9/44 • 30 days
|
4.8%
2/42 • 30 days
|
|
Nervous system disorders
Drowsiness
|
47.7%
21/44 • 30 days
|
23.8%
10/42 • 30 days
|
|
Gastrointestinal disorders
Nausea/Vomiting
|
6.8%
3/44 • 30 days
|
0.00%
0/42 • 30 days
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
2.3%
1/44 • 30 days
|
0.00%
0/42 • 30 days
|
|
Eye disorders
Vision Changes
|
4.5%
2/44 • 30 days
|
0.00%
0/42 • 30 days
|
|
Nervous system disorders
Headache
|
0.00%
0/44 • 30 days
|
2.4%
1/42 • 30 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/44 • 30 days
|
2.4%
1/42 • 30 days
|
|
Nervous system disorders
Lightheadedness
|
4.5%
2/44 • 30 days
|
0.00%
0/42 • 30 days
|
|
Eye disorders
Nystagmus
|
2.3%
1/44 • 30 days
|
0.00%
0/42 • 30 days
|
Additional Information
Theresa Frey, MD
Cincinnati Children's Hospital Medical Center
Phone: 513-636-7966
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place