Trial Outcomes & Findings for Release of Nociceptin From Granulocytes in Sepsis (NCT NCT03037281)
NCT ID: NCT03037281
Last Updated: 2021-01-06
Results Overview
Measure of N/OFQ presence in granulocytes and associated supernatant
Recruitment status
COMPLETED
Target enrollment
14 participants
Primary outcome timeframe
Day 1
Results posted on
2021-01-06
Participant Flow
Participant milestones
| Measure |
Septic
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
|
Overall Study
COMPLETED
|
6
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Septic
n=6 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers
n=8 Participants
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=14 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=14 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=6 Participants
|
8 Participants
n=8 Participants
|
13 Participants
n=14 Participants
|
|
Age, Continuous
|
75.5 years
n=6 Participants
|
34.5 years
n=8 Participants
|
52 years
n=14 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=6 Participants
|
6 Participants
n=8 Participants
|
9 Participants
n=14 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=6 Participants
|
2 Participants
n=8 Participants
|
5 Participants
n=14 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=6 Participants
|
8 participants
n=8 Participants
|
14 participants
n=14 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: Biosensor cells
Measure of N/OFQ presence in granulocytes and associated supernatant
Outcome measures
| Measure |
Septic
n=138 Biosensor cells
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
n=40 Biosensor cells
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
n=258 Biosensor cells
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
n=210 Biosensor cells
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
n=184 Biosensor cells
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
n=410 Biosensor cells
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Proportion of Responsive Biosensor Cells Responding to Granulocyte Addition in the Presence and Absence of NOP Antagonist
Eosinophils
|
34.25907426 mean % responsive biosensor cells
Standard Deviation 26.36477836
|
5.882352941 mean % responsive biosensor cells
Standard Deviation NA
Insufficient number of responsive cells as a fraction of overall number of cells extracted to allow SD to be calculated.
|
44.17193917 mean % responsive biosensor cells
Standard Deviation 30.09734468
|
25.13095238 mean % responsive biosensor cells
Standard Deviation 31.52494693
|
17.86976912 mean % responsive biosensor cells
Standard Deviation 14.33561565
|
39.97303622 mean % responsive biosensor cells
Standard Deviation 32.13672569
|
|
Proportion of Responsive Biosensor Cells Responding to Granulocyte Addition in the Presence and Absence of NOP Antagonist
Neutrophils
|
25.73232323 mean % responsive biosensor cells
Standard Deviation 25.95276607
|
8.712121212 mean % responsive biosensor cells
Standard Deviation 0.535686955
|
48.66792929 mean % responsive biosensor cells
Standard Deviation 37.86453531
|
32.34442641 mean % responsive biosensor cells
Standard Deviation 22.5667298
|
12.87518038 mean % responsive biosensor cells
Standard Deviation 20.00326171
|
17.06777597 mean % responsive biosensor cells
Standard Deviation 15.88672067
|
SECONDARY outcome
Timeframe: Day 1Count of the number of neutrophils in the original sample
Outcome measures
| Measure |
Septic
n=6 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
n=8 Participants
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Granulocyte Count
Neutrophils
|
5.07 x10^7 cells ml-1
Interval 3.33 to 6.4
|
2.05 x10^7 cells ml-1
Interval 0.94 to 3.4
|
—
|
—
|
—
|
—
|
|
Granulocyte Count
Eosinophils
|
0.98 x10^7 cells ml-1
Interval 0.4 to 1.9
|
1.61 x10^7 cells ml-1
Interval 0.53 to 2.44
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 daysAll cause mortality at 30 days
Outcome measures
| Measure |
Septic
n=6 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
n=8 Participants
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Mortality In-hospital, at 30 Days
|
3 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Time to ICU discharge (or death if on ICU)Outcome measures
| Measure |
Septic
n=4 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Time to ICU Discharge (or Death if on ICU)
|
7.5 days
Interval 3.0 to 24.0
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Number of days between admission and death or discharge from hospitalTime to death or discharge (days)
Outcome measures
| Measure |
Septic
n=6 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Time to Death or Discharge
|
17.5 days
Interval 3.0 to 59.0
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1The Acute Physiology and Chronic Health Evaluation (APACHE-2) score for the patient. APACHE 2 is an international standard,12 variable score from 0-71 reflecting disease severity in the critically unwell during the first 24 hours of illness. The score is a combined measure of illness severity (acute physiology), and background chronic health factors. Increased score represents increased predicted mortality. Variables recorded include AaDO2 or PaO2 (depending on FiO2), temperature, mean arterial pressure, blood pH, heart rate, respiratory rate, serum sodium, serum potassium, creatinine, hematocrit, white blood cell count, Glasgow Coma Scale Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985). "APACHE II: a severity of disease classification system". Critical Care Medicine. 13 (10): 818-29
Outcome measures
| Measure |
Septic
n=6 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Acute Physiology and Chronic Health Evaluation (APACHE-2) Score
|
19.8 score on a scale
Interval 6.0 to 31.0
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1The Sequential Organ Failure Assessment (SOFA) score for the patient, a score predictive of mortality in sepsis for intensive care patients based on respiratory, cardiovascular, hepatic, coagulation, renal and neurological function (each scored 0-4, with a maximum overall score of 24). The worst (most deranged) physiological values for the first 24 hours are used. A higher score predicts increased mortality. The mortality breakdown for each sofa score range is - SOFA 0-6 (\<10% mortality), 7-9 (15-20%), 10-12 (40-50%), 13-14 (50 - 60%), 15 (\> 80%), 16 to 24 (\> 90%)
Outcome measures
| Measure |
Septic
n=6 Participants
Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Septic (+NOP Antagonist SB612111)
Cells harvested from patients with sepsis, treated in an environment containing the NOP antagonist SB612111
|
Septic (N/OFQ Control)
Control treatment of biosensor cells with N/OFQ as a control
|
Healthy Volunteers
Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.
Septic: 30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.
|
Healthy Volunteers (+NOP Antagonist SB612111)
Cells harvested from healthy volunteers in an environment containing the NOP antagonist SB612111
|
Healthy Volunteers (N/OFQ Control)
Cells taken from healthy volunteers treated with N/OFQ as a control
|
|---|---|---|---|---|---|---|
|
Sequential Organ Failure Assessment (SOFA) Score
|
9.33 score on a scale
Interval 5.0 to 12.0
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Septic
Serious events: 0 serious events
Other events: 0 other events
Deaths: 3 deaths
Healthy Volunteers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place