Clinical Trial Results:
Skin bacteria as a source of surgical infections: molecular epidemiology and prevention of wound contamination
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Summary
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EudraCT number |
2009-016566-82 |
Trial protocol |
GB |
Global end of trial date |
07 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Jun 2022
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First version publication date |
25 Jun 2022
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Other versions |
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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 |
05/SP/120
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Additional study identifiers
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ISRCTN number |
ISRCTN73863246 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Belfast Health and Social Care Trust
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Sponsor organisation address |
Research Office, 2nd floor King Edward Building, Royal Hospital Site, Belfast, United Kingdom, BT12 6BA
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Public contact |
Alison Murphy, Research Office, Belfast Health and Social Care Trust , ResearchSponsor@belfasttrust.hscni.net
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Scientific contact |
Research Office, Belfast Health and Social Care Trust, ResearchSponsor@belfasttrust.hscni.net
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Sponsor organisation name |
Queen's University Belfast (QUB)
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Sponsor organisation address |
Research Governance, Ethics and Integrity, QUB, 63 University Road, Belfast, United Kingdom, BT7 1NN
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Public contact |
researchgovernance@qub.ac.uk, Research Governance, Ethics and Integrity, QUB
, 028 90972572, researchgovernance@qub.ac.uk
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Scientific contact |
researchgovernance@qub.ac.uk, Research Governance, Ethics and Integrity, QUB
, 028 90972572, researchgovernance@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 |
07 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Jul 2014
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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 aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery.
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Protection of trial subjects |
The following exclusion criteria were applied:
Patients who had more than 7 days in hospital prior to surgery.
Patients who had been transferred from another hospital, i.e. patients who had been inpatients in another hospital and transferred for surgery.
Patients with overt spinal infections suspected pre-operatively, or where evidence of purulence in any part of the wound is observed
during surgery.
Patients who were sensitive or allergic to the skin antiseptics.
Patients on antibiotics prior to surgery as antibiotics can be excreted in sweat and could therefore affect the normal resident microbiota.
Patients aged less than 18 years.
Pregnant women.
A data monitoring committee was also convened for the trial.
As the intervention being investigated was part of a routine surgical procedure no other protections were required.
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Background therapy |
Not applicable. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 May 2010
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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: 407
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Worldwide total number of subjects |
407
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EEA total number of subjects |
407
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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) |
350
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From 65 to 84 years |
56
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85 years and over |
1
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Recruitment
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Recruitment details |
Patients admitted for spinal surgery (Belfast Trust) were invited to participate in the study at pre-op assessment (4 to 6 months prior to their operation). Following admission 408 patients were recruited to the trial between 23/05/2010 and 07/07/2014. | |||||||||
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Pre-assignment
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Screening details |
All patients undergoing elective spinal surgery were screened and invited to participate in the study at a preoperative visit or by letter. 557 patients were approached and screened in accordance with the trial inclusion/exclusion criteria. 149 patients were deemed ineligible and were not recruited. | |||||||||
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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 |
Single blind [1] | |||||||||
Roles blinded |
Investigator, Data analyst [2] | |||||||||
Blinding implementation details |
The randomisation schedule was generated before the start of the trial by a statistician not involved in the trial or assessing outcomes. The trial was open label to the patients and hospital staff as the antiseptics were different colours and formulations. The principal investigator and staff who analysed and recorded bacterial culture from samples were however blinded to the treatment group.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm 1 | |||||||||
Arm description |
Patient skin disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
PVI (povidone iodine; Videne Alcoholic Tincture)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cutaneous solution, Cutaneous solution + medicated sponge
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Routes of administration |
Cutaneous use
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Dosage and administration details |
10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, applied neat, twice to skin surface before surgery.
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Arm title
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Arm 2 | |||||||||
Arm description |
Patient skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
PVI (povidone iodine; Videne Alcoholic Tincture) CHG (chlorhexidine gluconate; Chloraprep with tint)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cutaneous solution, Cutaneous solution + medicated sponge
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Routes of administration |
Cutaneous use
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Dosage and administration details |
10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, applied once neat to skin surface followed by 2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol, applied once neat to skin surface before surgery.
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| Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: The trial was open label to the patients and hospital staff as the antiseptics were different colours and formulations. The principal investigator and staff who analysed and recorded bacterial culture from samples were however blinded to the treatment group. [2] - The roles blinded appear inconsistent with a simple blinded trial. Justification: The trial was open label to the patients and hospital staff as the antiseptics were different colours and formulations. The principal investigator and staff who analysed and recorded bacterial culture from samples were however blinded to the treatment group. |
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Baseline characteristics reporting groups
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Reporting group title |
Arm 1
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Reporting group description |
Patient skin disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm 2
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Reporting group description |
Patient skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm 1
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Reporting group description |
Patient skin disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice. | ||
Reporting group title |
Arm 2
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Reporting group description |
Patient skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). | ||
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End point title |
Culture-positive | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
Culture-positive | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 1 v Arm 2
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.009 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.574
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.38 | |||||||||
upper limit |
0.866 | |||||||||
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End point title |
Internal samples culture-positive | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
Internal samples culture-positive | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 2 v Arm 1
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.011 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.545
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.344 | |||||||||
upper limit |
0.862 | |||||||||
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End point title |
Aerobic Culture-Positive | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
Aerobic Culture-Positive | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 1 v Arm 2
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.001 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.386
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.219 | |||||||||
upper limit |
0.681 | |||||||||
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End point title |
Anaerobic Culture-Positive | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
Anaerobic Culture-Positive | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 2 v Arm 1
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.047 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.648
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.429 | |||||||||
upper limit |
0.98 | |||||||||
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End point title |
High total viable count | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
High total viable count | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 1 v Arm 2
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.036 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.616
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.398 | |||||||||
upper limit |
0.955 | |||||||||
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End point title |
High aerobic total viable count | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
High aerobic total viable count | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 1 v Arm 2
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.028 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.408
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.189 | |||||||||
upper limit |
0.88 | |||||||||
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End point title |
High anaerobic total viable count | |||||||||
End point description |
Several different samples were taken during first 20mins of surgery and immediately stored under anaerobic conditions.
These were then transported to the lab and processed (destructively) asap same day.
Aliquots of processed samples were grown on a range of agar media, under both anaerobic and aerobic conditions, for 1 week.
After 1 week, cross-section of morphologically different isolates were removed from agar plates and subjected to molecular analysis.
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End point type |
Primary
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End point timeframe |
After surgical incisions have been performed
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Statistical analysis title |
High anaerobic total viable count | |||||||||
Statistical analysis description |
Proportion of patients with bacterial contamination of surgical site samples after skin disinfection
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Comparison groups |
Arm 1 v Arm 2
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Number of subjects included in analysis |
407
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.059 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.644
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.415 | |||||||||
upper limit |
1 | |||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
The timeframe for reporting of AE and SAEs was three months after the collection of the last sample of each patient.
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Assessment type |
Systematic | ||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||||||||
Dictionary version |
2
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Reporting groups
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Reporting group title |
Arm 2 PVI + CHG
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Reporting group description |
- | ||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There was one serious adverse event reported for the study and no non-serious adverse events reported. |
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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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08 Jan 2010 |
Protocol version 1.2: Protocol amendment |
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28 Jan 2010 |
Protocol version 1.3:Amendment to letter of invitation to participant |
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23 May 2011 |
Protocol version 1.5: Change to exclusion criteria in protocol: Number of days in hospital prior to surgery increased from no more than 2 to no more than 7 to increase recruitment rate. |
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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/28963158 |
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