Clinical Trial Results:
Prevention by HMGCoA reductase inhibition of ALI associated with one lung ventilation following oesophagectomy by a Reduction of Pulmonary vascular dysfunction and inflammation (Prevention-HARP)
Summary
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EudraCT number |
2007-002454-37 |
Trial protocol |
GB |
Global end of trial date |
10 Nov 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Mar 2020
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First version publication date |
08 Mar 2020
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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 |
RGHT000392
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Additional study identifiers
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ISRCTN number |
ISRCTN56543987 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Belfast Health & Social Care Trust (BHSCT)
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Sponsor organisation address |
King Edward Building, Royal Hospitals, Grosvenor Road,, Belfast, United Kingdom,
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Public contact |
Prof Daniel McAuley, Queen's University of Belfast, 02890 976385, d.f.mcauley@qub.ac.uk
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Scientific contact |
Prof Daniel McAuley, Queen's University of Belfast, 02890 976385, d.f.mcauley@qub.ac.uk
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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 |
10 Nov 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Nov 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Nov 2013
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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 |
The hypothesis of the study is that treatment with simvastatin can prevent lung injury and inflammation in humans undergoing oesophagectomy as assessed by important surrogate clinical outcomes.
The primary outcome is to evaluate the efficacy of simvastatin to improve pulmonary vascular function between the simvastatin and placebo treated groups
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Protection of trial subjects |
A Clinical Trials Monitor monitored study site compliance with study and CTU SOPs and provided feedback on any actual or potential problems in relation to safeguarding patients safety and wellbeing.
A DMEC was appointed comprising two clinicians with experience in undertaking clinical trials / caring for critically ill patients and a statistician. The DMEC met regularly and meetings were formally minuted. The DMEC’s responsibility was to safeguard the interests of the trial participants, in particular with regard to safety. The DMEC monitored recruitment and adverse events.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Aug 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United Kingdom: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
39
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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) |
22
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From 65 to 84 years |
17
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 102 patients, who were due to undergo esophagectomy, were assessed for eligibility between July 2007 and July 2010. 39 patients fulfilled the eligibility criteria and were enrolled into the trial. | |||||||||||||||
Pre-assignment
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Screening details |
Inclusion criteria Adult patients undergoing oesophagectomy for oesophageal cancer at the Royal Victoria Hospital, Belfast (RVH) were eligible for inclusion in the study. Patients were identified prior to surgery at the oesophageal cancer multi-disciplinary meeting. | |||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Investigator, Monitor, Assessor, Subject | |||||||||||||||
Blinding implementation details |
Simvastatin 80 mg or placebo (1:1) were encapsulated and in identical containers to ensure blinding.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Simvastatin | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Simvastatin
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Investigational medicinal product code |
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Other name |
Simvastatin
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Pharmaceutical forms |
Capsule
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Routes of administration |
Gastroenteral use
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Dosage and administration details |
Simvastatin 80mg for 4 days preoperatively and for 7 days postoperatively.
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Arm title
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Placebo | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Gastroenteral use
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Dosage and administration details |
For 4 days pre-operatively and 7 days post-operatively.
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Baseline characteristics reporting groups
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Reporting group title |
Simvastatin
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Simvastatin
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- |
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End point title |
pulmonary dead space (Vd/Vt) at 6 hours | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at 6 hours following oesophagectomy or prior to extubation
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Statistical analysis title |
Deadspace at 6 hours t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.2 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Compliance | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at 6 hours following one lung ventilation or prior to extubation if earlier
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Statistical analysis title |
Compliance t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.9 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
PaO2/FiO2 ratio | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
following oesophagectomy
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Statistical analysis title |
PaO2/FiO2 ratio t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.8 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Aspartate aminotransferase at day 4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 4
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Statistical analysis title |
Aspartate aminotransferase Day 4 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.8 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Aspartate aminotransferase at day 11 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 11
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Statistical analysis title |
Aspartate aminotransferase day 11 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.9 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Alanine aminotransferase day 4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 4
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Statistical analysis title |
Alanine aminotransferase day 4 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.6 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Alanine aminotransferase day 11 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 11
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Statistical analysis title |
Alanine aminotransferase day 11 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.8 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Creatine kinase at day 4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 4
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Statistical analysis title |
Creatine kinase day 4 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.03 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Creatine kinase at day 11 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 11
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Statistical analysis title |
Creatine kinase day 11 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 1 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Creatinine at day 4 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 4
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Statistical analysis title |
Creatinine day 4 t-test | ||||||||||||
Comparison groups |
Placebo v Simvastatin
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.4 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Safety Profile - Creatinine at day 11 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
at day 11
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Statistical analysis title |
Creatinine day 11 t-test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.9 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Plasma Rage- D0 pre-OLV | ||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
D0 pre-OLV
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Statistical analysis title |
Plasma Rage D0 pre-OLV 2-way ANOVA | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.02 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Plasma Rage D0 post-OLV | ||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
D0 post-OLV
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Statistical analysis title |
Plasma Rage D0 post-OLV 2-way ANOVA | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.02 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Plasma Rage Day 3 | ||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
Day 3
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Statistical analysis title |
Plasma Rage Day 3 2-way ANOVA | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.02 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Plasma Rage Day 7 | ||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
Day 7
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Statistical analysis title |
Plasma Rage Day 3 2-way ANOVA | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.02 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Hospital Outcomes - ALI | |||||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
until discharge
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Statistical analysis title |
Hospital Outcome ALI Fisher exact test | |||||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.1 | |||||||||||||||
Method |
Fisher exact | |||||||||||||||
Confidence interval |
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End point title |
Hospital Outcomes - Complications | ||||||||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
until discharge
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Statistical analysis title |
Complications Fisher exact test | ||||||||||||||||||
Statistical analysis description |
cardiac, respiratory and infective complications
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Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.29 | ||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||
Confidence interval |
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End point title |
Hospital Outcomes - ICU readmission | |||||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
until discharge
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Statistical analysis title |
Hospital Outcomes- ICU readmission Fisher exact | |||||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.33 | |||||||||||||||
Method |
Fisher exact | |||||||||||||||
Confidence interval |
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End point title |
Hospital Outcome Total Ventilator Days | ||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
until discharge
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Statistical analysis title |
Hospital Outcomes- Total Ventilator Days | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Hospital Outcomes- Total Hospital Stay | ||||||||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
Until discharge
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Statistical analysis title |
Hospital Outcome- Total Hospital Stay t test | ||||||||||||
Comparison groups |
Simvastatin v Placebo
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.26 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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Adverse events information
|
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Timeframe for reporting adverse events |
Up to day 7
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTC AE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Simvastatin
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Nov 2007 |
In the event of delay and postponement of the surgery the study medication will be stopped and then restarted 4 days prior to the new date of surgery.
Above info added to intervention section 3.3 of protocol
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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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/23817506 |