Clinical Trial Results:
Antibiotic Prophylaxis and Intervention for Postpartum Infections following Caesarean Section
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Summary
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EudraCT number |
2012-002068-29 |
Trial protocol |
DK |
Global end of trial date |
30 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Oct 2021
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First version publication date |
09 Oct 2021
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Other versions |
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Summary report(s) |
Unpublished data |
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 |
1-09-09-2012
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02072798 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Southern Denmark
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Sponsor organisation address |
Kloevervaenget 10, 10. floor, Odense, Denmark, 5000
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Public contact |
Nana Hyldig, Odense University Hospital, 0045 64415156, nana.hyldig@ouh.regionsyddanmark.dk
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Scientific contact |
Nana Hyldig, Odense University Hospital, 0045 64415156, nana.hyldig@ouh.regionsyddanmark.dk
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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 |
31 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Apr 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Apr 2015
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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 main large-scale trial was altered into a smaller pilot study with the object to investigate the timing of prophylactic antibiotics in women undergoing CS, with particular focus on maternal and neonatal outcomes
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Protection of trial subjects |
na
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Background therapy |
Participants in both groups received a single dose of intravenous cefuroxime 1.5 g dissolved in 100 ml NaCl. Cefuroxime, a second-generation cephalosporin, is the standard prophylaxis recommended in the Danish National Guidelines and has been selected because it is active against streptococci, staphylococci, and most enterobacteria. | ||
Evidence for comparator |
The effect of prophylactic antibiotics is optimal if the dose is administrated in the hour before the surgical incision, and the risk can be reduced further if the antibiotic is administrated in the 30 minutes prior to incision. Administration more than two hours before or after the incision increases the risk of SSI due to insufficient concentration of antibiotics in the surgical field. However, previously the recommendation was a single dose of antibiotic administered immediately after umbilical cord clamping, rather than preoperatively, to avoid placental transfer. Subsequently, individual studies and systematic reviews have demonstrated that pre-incision antibiotic prophylaxis compared to that after cord clamping is advantageous for the mother with no apparent disadvantage to the neonate. As a result, countries such as the United States, England and Canada have changed their national guidelines recommending that the timing should be 15 to 60 minutes prior to skin incision. The neonatal outcomes most frequently studied are neonatal sepsis, neonatal septic work-up and admission to the special care baby unit. No studies report on placental transfer of antibiotics, the possible effects on the neonatal gut micobiome, or long-term follow-up. | ||
Actual start date of recruitment |
28 Jan 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research, Safety | ||
Long term follow-up duration |
1 Months | ||
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 |
Denmark: 42
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Worldwide total number of subjects |
42
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EEA total number of subjects |
42
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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) |
42
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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 |
All women giving brith by elective CS at Odense University Hospital were informed the day before her planned elective CS by a project nurse, who handed out written together with oral information. Women declining participation received iv. Cefuroxim 1,5g post umbilical cord clamping, as standard practice at the time of the project. | |||||||||
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Pre-assignment
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Screening details |
Inclusion criteria: Age ≥ 18 year, able to read and understand Danish, gestation age ≥ 28 weeks, BMI < 30 kg/m2. Exclusion criteria: Hypersensitivity to cephalosporin antibiotics, previous severe reaction to penicillin, systemic exposure to any antibiotic agent within 1 week before CS, very sick newborn infants treated with antibiotic. | |||||||||
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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 |
Not blinded | |||||||||
Blinding implementation details |
The pilot study is a non-blinded RCT because we only want to collect blood samples from infants delivered by mothers in the intervention group. Thus, to avoid taking blood sample from infants in the control group, the study was unblinded.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention arm | |||||||||
Arm description |
Participants in the intervention arm was given 1500 mg iv Cefuroxim administrated 15 to 60 minuts before the caesarean section incision was made. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Cefuroxime
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Investigational medicinal product code |
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Other name |
cephalosporin
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Pharmaceutical forms |
Concentrate and solvent for intravesical solution
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Routes of administration |
Intravenous use
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Dosage and administration details |
Cefuroxime is a second-generation cephalosporin. The summery product characteristics (SPC) of cefuroxime is described at the Danish Health and Medicines Authority’s webpage www.produktresume.dk
The woman in the intervention group was given 1500 mg iv Cefuroxime dissolved in 100 ml NaCl administrated 15 to 60 minutes before the surgical incision.
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Arm title
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Control arm | |||||||||
Arm description |
Participants in the control arm was given 1500 mg iv Cefuroxime after after umbilical cord clamping as current practice at the time of the study. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Cefuroxime
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Investigational medicinal product code |
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Other name |
cephalosporin
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Pharmaceutical forms |
Concentrate and solvent for intravesical solution
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Routes of administration |
Intravenous use
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Dosage and administration details |
Cefuroxime is a second-generation cephalosporin. The summery product characteristics (SPC) of cefuroxime is described at the Danish Health and Medicines Authority’s webpage www.produktresume.dk
The woman in the control group was given 1500 mg iv Cefuroxime dissolved in 100 ml NaCl administrated after umbilical cord clamping.
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Baseline characteristics reporting groups
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Reporting group title |
Intervention arm
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Reporting group description |
Participants in the intervention arm was given 1500 mg iv Cefuroxim administrated 15 to 60 minuts before the caesarean section incision was made. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control arm
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Reporting group description |
Participants in the control arm was given 1500 mg iv Cefuroxime after after umbilical cord clamping as current practice at the time of the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention arm
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Reporting group description |
Participants in the intervention arm was given 1500 mg iv Cefuroxim administrated 15 to 60 minuts before the caesarean section incision was made. | ||
Reporting group title |
Control arm
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Reporting group description |
Participants in the control arm was given 1500 mg iv Cefuroxime after after umbilical cord clamping as current practice at the time of the study. | ||
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End point title |
maternal infectious morbidity | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
from time of caesarean section undtil 30 days after surgery
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Statistical analysis title |
logistic regression | |||||||||
Comparison groups |
Intervention arm v Control arm
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Risk ratio (RR) | |||||||||
Point estimate |
0.26
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.06 | |||||||||
upper limit |
1.12 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
The day of caesarean section until 30 days after surgery
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Assessment type |
Systematic | ||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
non | ||||||||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
overall trial
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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? Yes | |||
Date |
Amendment |
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18 Dec 2013 |
The trial was original designed to investigate “Antibiotic prophylaxis and Intervention for postpartum infections following caesarean section” with focus on mothers giving birth by caesarean section. Due to lack of funding the trial was redesigned to be a a feasibility study with focus on the newborn infants: “Antibiotics and gut microbiota among newborn infants”. |
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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/31053348 http://www.ncbi.nlm.nih.gov/pubmed/27240549 |
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