Clinical Trial Results:
Antibiotic prophylaxis oral vs parenteral + parenteral in colonic surgery: a prospective, randomized, multicenter clinical trial.
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Summary
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EudraCT number |
2014-002345-21 |
Trial protocol |
ES |
Global end of trial date |
28 Apr 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Sep 2021
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First version publication date |
30 Sep 2021
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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 |
2011/001/PROF-ATB
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
VHIR
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Sponsor organisation address |
Passeig Vall dHebron 119-129, Barcelona, Spain, 08035
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Public contact |
VHIR/Technical Secretariat, Joaquin Lopez-Soriano, 34 934893807, joaquin.lopez.soriano@vhir.org
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Scientific contact |
Colorectal Surgery Unit, Dr Eloy Espin, 934893807 9342720006587, eespinbasany@gmail.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 |
28 Apr 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Apr 2017
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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 |
Patients undergoing colon surgery were recruited from five major hospitals in Spain. Patients were eligible for inclusion if they were diagnosed with neoplasia or diverticular disease and if a partial colon resection or total colectomy was indicated. Participants were randomly assigned to either administration of oral antibiotics the day before surgery (experimental group) or no administration of oral antibiotics before surgery (control group). For the experimental group, ciprofloxacin 750 mg was given every 12 h (two doses at 1200 h and 0000 h) and metronidazole 250 mg every 8 h (three doses at 1200 h, 1800 h, and 0000 h) the day before surgery. All patients were given intravenous cefuroxime 1·5 g and metronidazole 1 g at the time of anaesthetic induction. The primary outcome was incidence of surgical-site infections. Patients were followed up for 1 month after surgery and all postsurgical complications were registered.
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Protection of trial subjects |
The detection and evaluation of surgical-site infections and complications after surgery followed current clinical practice guidelines, consisting of daily physical examination of the patient in the immediate period after surgery and outpatient visits at the study centre in the first, second, and fourth weeks after surgery. All examinations for surgical-site infections were done by a nurse specialising in infections. Complementary tests for the screening of infections after surgery were blood tests, cultures of wound exudates of intra-abdominal abscesses, abdomen–pelvic CT, and surgical exploration.
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Background therapy |
Mechanical bowel preparation is a relevant confounder if associated with oral antibiotics. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Aug 2014
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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 |
Spain: 536
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Worldwide total number of subjects |
536
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EEA total number of subjects |
536
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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) |
501
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From 65 to 84 years |
35
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited from five hospitals in Spain: the Vall d’Hebron University Hospital (Barcelona), Bellvitge University Hospital (Barcelona), the Josep Trueta University Hospital (Girona), Lucus Augusti Hospital (Lugo), and the Cruces University Hospital (Bilbao). | |||||||||
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Pre-assignment
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Screening details |
Patients were eligible if they were diagnosed with neoplasia or diverticular disease and if a partial colon resection or total colectomy was indicated. Patients were excluded if they had been given antibiotic treatment in the 2 weeks before surgery or had undergone mechanical bowel preparation the day before surgery. | |||||||||
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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 | |||||||||
Roles blinded |
Monitor [1] | |||||||||
Blinding implementation details |
Patients were randomly assigned (1:1), using online randomisation software, stratified by study site, to two parallel groups, the control group (no oral antibiotics) or the experimental group (oral antibiotics). Randomisation was done by an external statistician.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Control | |||||||||
Arm description |
No oral antibiotics | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Cefuroxime
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1500 mg at the time of anaesthetic induction.
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Investigational medicinal product name |
Metronidazole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1 g at the time of anaesthetic induction.
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Arm title
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Oral antibiotic | |||||||||
Arm description |
The experimental group was treated with a regimen of ciprofloxacin 750 mg every 12 h (two doses at 1200 h and 0000 h) and metronidazole 250 mg every 8 h (three doses at 1200 h, 1800 h, and 0000 h) orally the day before the scheduled surgery. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Ciprofloxacin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ciprofloxacin 750 mg every 12 h (two doses at 1200 h and 0000 h) orally
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: The investigators, surgeons, patients, and statistician were unmasked to the group the patient was randomly assigned to, but the nurse who assessed the presence or absence of a surgical-site infection was masked to treatment assignment. |
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Baseline characteristics reporting groups
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Reporting group title |
Control
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Reporting group description |
No oral antibiotics | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oral antibiotic
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Reporting group description |
The experimental group was treated with a regimen of ciprofloxacin 750 mg every 12 h (two doses at 1200 h and 0000 h) and metronidazole 250 mg every 8 h (three doses at 1200 h, 1800 h, and 0000 h) orally the day before the scheduled surgery. | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Control
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Reporting group description |
No oral antibiotics | ||
Reporting group title |
Oral antibiotic
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Reporting group description |
The experimental group was treated with a regimen of ciprofloxacin 750 mg every 12 h (two doses at 1200 h and 0000 h) and metronidazole 250 mg every 8 h (three doses at 1200 h, 1800 h, and 0000 h) orally the day before the scheduled surgery. | ||
Subject analysis set title |
Full study
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients
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End point title |
Surgical-site infections | ||||||||||||
End point description |
The primary endpoint was the incidence of surgical-site infections, defined as the sum of skin superficial, deep incisional, and organ-space infections, according to the criteria of the US Centers for Disease Control and Prevention
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End point type |
Primary
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End point timeframe |
End of study
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Statistical analysis title |
Site infections | ||||||||||||
Comparison groups |
Control v Oral antibiotic
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Number of subjects included in analysis |
536
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.013 | ||||||||||||
Method |
Chi-squared | ||||||||||||
Confidence interval |
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End point title |
Duration of stay in hospital | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
End of study
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Statistical analysis title |
Stay in hospital | ||||||||||||
Comparison groups |
Control v Oral antibiotic
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Number of subjects included in analysis |
536
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.088 | ||||||||||||
Method |
Chi-squared | ||||||||||||
Confidence interval |
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End point title |
Time from surgery to infection detection | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
All the study
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Statistical analysis title |
Time to infection | ||||||||||||
Comparison groups |
Control v Oral antibiotic
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Number of subjects included in analysis |
536
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.115 | ||||||||||||
Method |
Chi-squared | ||||||||||||
Confidence interval |
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End point title |
Complication | ||||||||||||
End point description |
Not including surgical-site infection
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End point type |
Secondary
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End point timeframe |
All the study
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Statistical analysis title |
Complications | ||||||||||||
Comparison groups |
Control v Oral antibiotic
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Number of subjects included in analysis |
536
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.017 | ||||||||||||
Method |
Chi-squared | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All the study
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
14.1
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| 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: No adverse events associated with the oral antibiotics were recorded. A full list of local, surgical, and medical complications is given in the publication, recorded as secondary end points. |
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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. | |||
| Placebo was not used for the control group, which might be a source of bias. Additionally, surgeons and patients were not masked to treatment group assignment because of logistical issues, which could be regarded as a source of bias. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/32325012 |
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