Clinical Trial Results:
A RANDOMIZED, CONTROLLED, MULTICENTER PHASE 2 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FIBRIN SEALANT VH S/D 500 S-APR (TISSEEL) FOR HEMOSTASIS IN SUBJECTS UNDERGOING HEPATIC RESECTION
Summary
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EudraCT number |
2010-018480-42 |
Trial protocol |
DE |
Global end of trial date |
26 Jul 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Nov 2017
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First version publication date |
08 Nov 2017
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
550904
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01244425 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Baxter Healthcare Corporation
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Sponsor organisation address |
1 Baxter Parkway, Deerfield, United States, 60015
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Public contact |
Clinical Trials Disclosure Group, Baxter Healthcare Corporation, joe_archer@Baxter.com
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Scientific contact |
Clinical Trials Disclosure Group, Baxter Healthcare Corporation, joe_archer@Baxter.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Jul 2011
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Jul 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Jul 2011
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of FS VH S/D 500 s-apr for hemostasis in subjects undergoing partial hepatic resection, as compared to a control arm treated by manual compression with a surgical gauze swab.
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Protection of trial subjects |
If no hemostasis occurred within 10 minutes of treatment, the surgeon was free to use other additional hemostatic measures (ie, rescue therapy) as he/she felt appropriate. In the same way, the surgeon was, at any time in the procedure, free to abort study participation if convinced that medical circumstances made it necessary.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Nov 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 95
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Worldwide total number of subjects |
95
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EEA total number of subjects |
95
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
95
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were to undergo planned, elective resection of at least 1 anatomical segment of the liver for any reason by laparotomy. | ||||||||||||||||||
Pre-assignment
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Screening details |
Subjects were evaluated for eligibility at screening within 21 days prior to surgery, and enrolled as soon as informed consent was obtained after meeting all inclusion and exclusion criteria. A total of 95 subjects were enrolled, 25 subjects were not randomized (23 were screen failures, 2 discontinued). | ||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
95 | ||||||||||||||||||
Number of subjects completed |
70 | ||||||||||||||||||
Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Screen failures: 23 | ||||||||||||||||||
Reason: Number of subjects |
Operated by non-investigator: 1 | ||||||||||||||||||
Reason: Number of subjects |
Prolonged operation and IP could not be used: 1 | ||||||||||||||||||
Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | ||||||||||||||||||
Roles blinded |
Subject | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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FS VH S/D 500 s-apr | ||||||||||||||||||
Arm description |
Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr), sprayed onto the oozing resection surface of the liver, not to exceed 20mL per participant. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Fibrin Sealant (FS) VH S/D 500 s-apr
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Investigational medicinal product code |
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Other name |
Tisseel
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Pharmaceutical forms |
Sealant
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Routes of administration |
Topical use
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Dosage and administration details |
Single application, sprayed onto the oozing resection surface of the liver, not to exceed 20mL.
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Arm title
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Manual Compression | ||||||||||||||||||
Arm description |
A dry surgical gauze swab will be used to apply by hand an even light pressure onto the oozing resection surface of the liver. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline period represents subjects randomized into study, and included in both the Full Analysis Set (FAS) and Safety populations. Worldwide number reflects total number enrolled including those not randomized and those who did not receive treatment. |
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Baseline characteristics reporting groups
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Reporting group title |
FS VH S/D 500 s-apr
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Reporting group description |
Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr), sprayed onto the oozing resection surface of the liver, not to exceed 20mL per participant. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Manual Compression
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Reporting group description |
A dry surgical gauze swab will be used to apply by hand an even light pressure onto the oozing resection surface of the liver. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
FS VH S/D 500 s-apr
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Reporting group description |
Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr), sprayed onto the oozing resection surface of the liver, not to exceed 20mL per participant. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. | ||
Reporting group title |
Manual Compression
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Reporting group description |
A dry surgical gauze swab will be used to apply by hand an even light pressure onto the oozing resection surface of the liver. Hemostasis will be assessed at 4, 6, 8 and 10 minutes after application of the study treatment. |
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End point title |
Percentage of participants with intraoperative hemostasis at 4 minutes after application of the randomized treatment | ||||||||||||
End point description |
Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression.
The following were regarded as treatment failures:
- No hemostasis achieved at 4 minutes post treatment application (for the FS VH S/D 500 s-apr arm, the “time to hemostasis” was used; a time window of +5 seconds was acceptable for showing a success)
- Additional hemostatic treatment (ie, hemostatics in addition to the randomized treatment) was required
- Reapplication of FS VH S/D 500 s-apr after 4 minutes
- Intraoperative rebleeding after the first 4 minutes of the observation period
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End point type |
Primary
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End point timeframe |
4 minutes post start of treatment application
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
likelihood-ratio chi square test | ||||||||||||
Confidence interval |
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End point title |
Percentage of participants with intraoperative hemostasis at 6 minutes after application of the randomized treatment | ||||||||||||
End point description |
Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression.
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End point type |
Secondary
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End point timeframe |
6 minutes after start of treatment application
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
likelihood ratio chi-square test | ||||||||||||
Confidence interval |
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End point title |
Percentage of participants with intraoperative hemostasis at 8 minutes after application of the randomized treatment | ||||||||||||
End point description |
Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression.
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End point type |
Secondary
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End point timeframe |
8 minutes after start of treatment application
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.028 | ||||||||||||
Method |
likelihood ratio chi-square test | ||||||||||||
Confidence interval |
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End point title |
Percentage of participants with intraoperative hemostasis at 10 minutes after application of the randomized treatment | ||||||||||||
End point description |
Hemostasis defined as no visible bleeding on the liver resection surface (liver surgical site) after treatment application. Hemostasis had to be maintained until surgical closure. Time recording started with treatment application, ie, with the start of spraying Fibrin Sealant, Vapor Heated, Solvent/Detergent treated with 500 IU/mL thrombin and synthetic aprotinin (FS VH S/D 500 s-apr) or with the application of manual compression.
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End point type |
Secondary
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End point timeframe |
10 minutes after start of treatment application
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.017 | ||||||||||||
Method |
likelihood ratio chi-square test | ||||||||||||
Confidence interval |
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End point title |
Percentage of participants with intraoperative rebleeding after occurrence of hemostasis | ||||||||||||
End point description |
Intraoperative rebleeding from the treated liver resection surface after occurrence of hemostasis.
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End point type |
Secondary
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End point timeframe |
Intraoperative day 0
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.293 | ||||||||||||
Method |
likelihood ratio chi-square test | ||||||||||||
Confidence interval |
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End point title |
Percentage of participants with postoperative rebleeding | ||||||||||||
End point description |
Rebleeding until discharged from the surgical ward, defined as any rebleeding from the treated liver resection surface requiring surgical reexploration
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End point type |
Secondary
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End point timeframe |
Day 0 Postoperative until discharged from surgical ward (within 48 hours after end of surgery or longer)
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.237 | ||||||||||||
Method |
likelihood ratio chi-square test | ||||||||||||
Confidence interval |
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End point title |
Percentage of participants with transfusion requirements until discharged from surgical ward | ||||||||||||
End point description |
Transfusions administered included whole blood, packed red blood cells, fresh frozen plasma, and thrombocyte concentrate.
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End point type |
Secondary
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End point timeframe |
Day ) Intra- and Postoperative until discharged from surgical ward (within 48 hours after end of surgery or longer)
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Statistical analysis title |
Statistical Analysis | ||||||||||||
Comparison groups |
FS VH S/D 500 s-apr v Manual Compression
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.808 | ||||||||||||
Method |
likelihood ratio chi-square test | ||||||||||||
Confidence interval |
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End point title |
Median total volume of postoperative drainage fluid within 48 hours after surgery | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Within 48 hours after surgery
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Screening (within 21 days prior to surgery) through end of study (20-40 days after surgery)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
unspecific
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Reporting groups
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Reporting group title |
FS VH S/D 500 s-apr
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Manual Compression
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |