Trial Outcomes & Findings for Defibrotide in the Human Endotoxemia Model --- an Exploratory Trial Investigating the Effects and the Mechanisms of Defibrotide (NCT NCT02876601)
NCT ID: NCT02876601
Last Updated: 2019-12-19
Results Overview
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h. The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
20 participants
Primary outcome timeframe
The parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h.
Results posted on
2019-12-19
Participant Flow
This was a crossover study. Of 20 healthy volunteers 16 were randomly assigned to receive LPS, while 4 received Placebo only. All participants underwent two study periods: A defibrotide and a placebo period. The system will not let us enter this study design of a crossover study. Only 20 healthy volunteers participated.
Participant milestones
| Measure |
LPS+ First Defibrotide, Then Placebo
First Intervention:
LPS: 2ng/kg bodyweight Defibrotide: 6.25mg/kg bodyweight over 2h infusion
Washout for 6 weeks:
Second Intervention:
LPS: 2ng/kg bodyweight Placebo: 0.9% sodium chloride infusion over 2h infusion
|
LPS+ First Placebo, Then Defibrotide
First Intervention:
LPS: 2ng/kg bodyweight Placebo: 0.9% sodium chloride infusion over 2h infusion
Washout for 6 weeks:
Second Intervention:
LPS: 2ng/kg bodyweight Defibrotide: 6.25mg/kg bodyweight over 2h infusion
|
Placebo+ First Defibrotide, Then Placebo
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
First Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Defibrotide: 6.25mg/kg bodyweight Defibrotide over 2 hours
Washout: 6 weeks
Second Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Placebo: 0.9% sodium chloride solution infusion over 2h
|
Placebo+ First Placebo, Then Defibrotide
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
First Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Placebo: 0.9% sodium chloride solution infusion over 2h
Washout: 6 weeks
Second Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Defibrotide: 6.25mg/kg bodyweight Defibrotide over 2 hours
|
|---|---|---|---|---|
|
First Intervention (24 Hours)
STARTED
|
8
|
8
|
2
|
2
|
|
First Intervention (24 Hours)
COMPLETED
|
8
|
8
|
2
|
2
|
|
First Intervention (24 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Washout (Minimum of 6 Weeks)
STARTED
|
8
|
8
|
2
|
2
|
|
Washout (Minimum of 6 Weeks)
COMPLETED
|
8
|
8
|
1
|
2
|
|
Washout (Minimum of 6 Weeks)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Second Intervention (24 Hours)
STARTED
|
8
|
8
|
1
|
2
|
|
Second Intervention (24 Hours)
COMPLETED
|
8
|
8
|
1
|
2
|
|
Second Intervention (24 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
LPS+ First Defibrotide, Then Placebo
First Intervention:
LPS: 2ng/kg bodyweight Defibrotide: 6.25mg/kg bodyweight over 2h infusion
Washout for 6 weeks:
Second Intervention:
LPS: 2ng/kg bodyweight Placebo: 0.9% sodium chloride infusion over 2h infusion
|
LPS+ First Placebo, Then Defibrotide
First Intervention:
LPS: 2ng/kg bodyweight Placebo: 0.9% sodium chloride infusion over 2h infusion
Washout for 6 weeks:
Second Intervention:
LPS: 2ng/kg bodyweight Defibrotide: 6.25mg/kg bodyweight over 2h infusion
|
Placebo+ First Defibrotide, Then Placebo
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
First Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Defibrotide: 6.25mg/kg bodyweight Defibrotide over 2 hours
Washout: 6 weeks
Second Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Placebo: 0.9% sodium chloride solution infusion over 2h
|
Placebo+ First Placebo, Then Defibrotide
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
First Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Placebo: 0.9% sodium chloride solution infusion over 2h
Washout: 6 weeks
Second Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Defibrotide: 6.25mg/kg bodyweight Defibrotide over 2 hours
|
|---|---|---|---|---|
|
Washout (Minimum of 6 Weeks)
unforeseen unavailability
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
LPS+ First Defibrotide, Then Placebo
n=8 Participants
First Intervention:
LPS: 2ng/kg bodyweight Defibrotide: 6.25mg/kg bodyweight over 2h infusion
Washout for 6 weeks:
Second Intervention:
LPS: 2ng/kg bodyweight Placebo: 0.9% sodium chloride infusion over 2h infusion
|
LPS+ First Placebo, Then Defibrotide
n=8 Participants
First Intervention:
LPS: 2ng/kg bodyweight Placebo: 0.9% sodium chloride infusion over 2h infusion
Washout for 6 weeks:
Second Intervention:
LPS: 2ng/kg bodyweight Defibrotide: 6.25mg/kg bodyweight over 2h infusion
|
Placebo+ First Defibrotide, Then Placebo
n=2 Participants
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
First Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Defibrotide: 6.25mg/kg bodyweight Defibrotide over 2 hours
Washout: 6 weeks
Second Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Placebo: 0.9% sodium chloride solution infusion over 2h
|
Placebo+ First Placebo, Then Defibrotide
n=2 Participants
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
4 healthy volunteers were randomized not to receive LPS. However, they still received Placebo or Defibrotide. This group was included as another control group and to investigate the effects of Defibrotide in vivo.
First Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Placebo: 0.9% sodium chloride solution infusion over 2h
Washout: 6 weeks
Second Intervention:
Placebo: bolus infusion of 0.9% sodium chloride solution Defibrotide: 6.25mg/kg bodyweight Defibrotide over 2 hours
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=20 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
2 Participants
n=2 Participants
|
2 Participants
n=2 Participants
|
20 Participants
n=20 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=20 Participants
|
|
Age, Continuous
|
32 years
STANDARD_DEVIATION 9 • n=8 Participants
|
29 years
STANDARD_DEVIATION 7 • n=8 Participants
|
41 years
STANDARD_DEVIATION 8 • n=2 Participants
|
21 years
STANDARD_DEVIATION 0 • n=2 Participants
|
31 years
STANDARD_DEVIATION 9 • n=20 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=2 Participants
|
2 Participants
n=2 Participants
|
2 Participants
n=20 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
2 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
18 Participants
n=20 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Austria
|
8 participants
n=8 Participants
|
8 participants
n=8 Participants
|
2 participants
n=2 Participants
|
2 participants
n=2 Participants
|
20 participants
n=20 Participants
|
PRIMARY outcome
Timeframe: The parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h. The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Prothrombin Fragments f1+2
|
31.1 fold-change*h
Interval 16.96 to 61.6
|
34.08 fold-change*h
Interval 20.38 to 60.8
|
27.41 fold-change*h
Interval 27.21 to 46.48
|
36.02 fold-change*h
Interval 23.64 to 51.95
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h. The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Thrombin-Antithrombin Complexes
|
23.39 fold*h
Interval 15.19 to 32.52
|
27.4 fold*h
Interval 21.47 to 41.57
|
17.46 fold*h
Interval 15.58 to 20.46
|
21.83 fold*h
Interval 16.09 to 23.26
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, and 6h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h. The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Plasmin-Antiplasmin Complexes
|
11.8 fold*h
Interval 9.59 to 15.12
|
9.99 fold*h
Interval 8.15 to 13.16
|
7 fold*h
Interval 6.31 to 7.19
|
7.12 fold*h
Interval 6.34 to 7.79
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Tumor Necrosis Factor (TNF)-Alpha
|
286 fold*h
Interval 162.0 to 453.0
|
326 fold*h
Interval 172.0 to 366.0
|
28.08 fold*h
Interval 22.19 to 28.35
|
21.01 fold*h
Interval 16.75 to 25.27
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Tissue-type Plasminogen Activator
|
21.8 fold*h
Interval 14.9 to 29.3
|
17 fold*h
Interval 13.9 to 23.9
|
20.57 fold*h
Interval 19.75 to 21.45
|
23.54 fold*h
Interval 21.72 to 24.78
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Interleukin-6
|
1543 fold*h
Interval 815.0 to 2919.0
|
1144 fold*h
Interval 22.0 to 1923.0
|
35 fold*h
Interval 32.0 to 113.0
|
31 fold*h
Interval 23.0 to 51.0
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
E-Selectin
|
35 fold*h
Interval 32.0 to 40.0
|
33 fold*h
Interval 24.0 to 45.0
|
21 fold*h
Interval 18.0 to 36.0
|
41 fold*h
Interval 20.0 to 63.0
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Plasminogen Activator Inhibitor 1
|
216 fold*h
Interval 32.0 to 898.0
|
477 fold*h
Interval 49.0 to 1000.0
|
25 fold*h
Interval 25.0 to 29.5
|
24.86 fold*h
Interval 22.7 to 25.0
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison.
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The quantification of von Willebrand Factor is based on reference values and results are in % of "normal". The respective arbitrary unit therefore is %\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Von Willebrand Factor Antigen
|
54 %*h
Interval 41.0 to 70.0
|
53 %*h
Interval 41.0 to 65.0
|
27 %*h
Interval 27.0 to 31.0
|
26 %*h
Interval 24.0 to 29.0
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h, 24h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison.
In this analysis, first of all a ratio of the measurement time point to the baseline was calculated. Thereafter deltas (baeline-ratio) were calculated. With the results an AUC was calculated. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Clotting Time in Thromboelastometry
|
1.12 fold*h
Interval 0.8 to 1.43
|
1.12 fold*h
Interval 1.04 to 1.41
|
-0.2 fold*h
Interval -6.0 to 2.17
|
2.14 fold*h
Interval 0.31 to 4.28
|
SECONDARY outcome
Timeframe: This parameter was assessed at baseline, at 0h, 1h, 2h, 4h, 6h and AUC was calculated based on these measurements.Population: The main statistical comparison was done for all subjects receiving LPS (defibrotide vs. placebo). The "placebo period" (4 subjects who did not receive lipopolysaccharide) was only included for a descriptive comparison, but not for statistical comparison.
Based on the changes from baseline an area-under the concentration-time curve will be calculated and will be compared between the placebo and the verum phase within each subject. The respective arbitrary unit therefore is fold\*h.
Outcome measures
| Measure |
LPS Plus Defibrotide
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
LPS Plus Placebo
n=16 Participants
Intervention: 6.25mg/kg bodyweight defibrotide plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Defibrotide
n=3 Participants
Intervention: placebo infusion (0.9% sodium chloride) plus 2ng/kg bodyweight LPS bolus infusion
|
Placebo Plus Placebo
n=4 Participants
Intervention: placebo (0.9% sodium chloride) infusion placebo bolus infusion (0.9% sodium chloride)
|
|---|---|---|---|---|
|
Maximum Lysis in Thromboelastometry
|
7.9 fold*h
Interval 7.1 to 10.1
|
7.7 fold*h
Interval 6.6 to 9.0
|
6.84 fold*h
Interval 6.72 to 7.07
|
6.85 fold*h
Interval 6.32 to 7.05
|
Adverse Events
Defibrotide Plus LPS
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Placebo Plus LPS
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Defibrotide Plus Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo/Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Defibrotide Plus LPS
n=16 participants at risk
Intervention: 6.25mg/kg bodyweight defibrotide infusion plus 2ng/kg bodyweight LPS infusion
|
Placebo Plus LPS
n=16 participants at risk
Intervention: placebo infusion (0.9% sodium chloride solution) plus 2ng/kg bodyweight LPS infusion
|
Defibrotide Plus Placebo
n=3 participants at risk
Intervention: 6.25mg/kg bodyweight defibrotide infusion plus placebo bolus infusion (0.9% sodium chloride solution)
|
Placebo/Placebo
n=4 participants at risk
Intervention: placebo infusion (0.9% sodium chloride solution) plus placebo bolus infusion (0.9% sodium chloride solution)
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
81.2%
13/16 • Number of events 13 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
68.8%
11/16 • Number of events 11 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
25.0%
1/4 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
Nervous system disorders
Vertigo
|
6.2%
1/16 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Flu-like Symptoms
|
37.5%
6/16 • Number of events 6 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
37.5%
6/16 • Number of events 6 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Arthralgia
|
12.5%
2/16 • Number of events 2 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
43.8%
7/16 • Number of events 7 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Chills
|
18.8%
3/16 • Number of events 3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
37.5%
6/16 • Number of events 6 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Impaired Concentration
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
6.2%
1/16 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Fatigue
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
6.2%
1/16 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Precollapse
|
6.2%
1/16 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Dizziness
|
6.2%
1/16 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
General disorders
Nausea
|
12.5%
2/16 • Number of events 2 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
6.2%
1/16 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/3 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
|
Skin and subcutaneous tissue disorders
Urticarial rash
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/16 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
33.3%
1/3 • Number of events 1 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
0.00%
0/4 • For the individual subject, adverse events were assessed during every study visit (screening, study day1, study day 2, follow up) during the whole study. The whole study period lastet for a minimum of 8 weeks, but could be longer for individual subjects (washout period was a minimum of 6 weeks). The respective time frame could therefore differ between the individual subjects but was a minimum of 8 weeks.
|
Additional Information
Univ.Prof. Dr. Bernd Jilma
Medical University of Vienna
Phone: +4314040029810
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place