Condition category
Neonatal Diseases
Date applied
25/05/2020
Date assigned
28/05/2020
Last edited
28/05/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Sepsis is a life-threatening reaction to an infection, and early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic treatment in newborns with a negative blood test. Overuse of antibiotics may lead to increased antibiotic-resistant bacteria. Antibiotic treatment in term newborns has also been associated with increased risks of asthma, wheezing, food allergy and childhood obesity. The aim of this study is to find out whether an intervention could reduce unwarranted antibiotic use in a safe way in term newborns with culture-negative sepsis.

Who can participate?
All term newborns (week 37 + 0 to week 41 + 6) treated for EOS at Ryhov Hospital, Jönköping, Sweden before (period 1: 2016-2017) and after the intervention (period 2: 11 June 2018 to 30 September 2019). In the study, EOS was defined as onset of symptoms within 72 hours of life.

What does the study involve?
The intervention includes new treatment guidelines including C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic treatment in term newborns meeting the criteria of the new treatment guidelines. Before the new guidelines were introduced, newborns with EOS used to be treated with at least seven days of intravenous antibiotics at the neonatal intensive care unit. According to the new treatment guidelines, the intravenous antibiotic therapy can be withdrawn after three days followed by administration of oral suspension antibiotic (amoxicillin, 20 mg/kg three times a day) for two more days in term newborns meeting the criteria of the new treatment guidelines. In the study newborns with EOS receive benzylpenicillin 50 mg/kg every 8-12 hours and amikacin 15 mg/kg every 24 hours. The new guidelines contain the following criteria: term newborn (week 37 + 0 to week 41 + 6), no need for intensive care (including invasive respiratory [breathing] support or cardiovascular [heart] support) initially when the antibiotic treatment started, the newborn appears well on day 3, the blood culture is not positive on day 3 and maximum CRP value of 80 mg/l decreasing by at least 50% during the first three days. In the study, newborns with EOS meeting the criteria of the guidelines are compared before and after the implementation of the guidelines.

What are the possible benefits and risks of participating?
Reduced antibiotic use may lead to fewer side effects of antibiotic treatment and a shorter hospital stay which is beneficial for the patient. Reduced antibiotic use may potentially increase the risk of reinfection or readmission in infected newborns.

Where is the study run from?
Ryhov Hospital (Sweden)

When is the study starting and how long is it expected to run for?
February 2018 to May 2020

Who is funding the study?
This study was financed by Ryhov County Hospital, Futurum - the academy for healthcare, Region Jönköping County, and grants from the Swedish state under an agreement between the Swedish government and the county council, the ALF agreement

Who is the main contact?
Johan Gyllensvärd
johan.gyllensvard@rjl.se

Trial website

Contact information

Type

Scientific

Primary contact

Mr Johan Gyllensvärd

ORCID ID

https://orcid.org/0000-0002-8671-6346

Contact details

Barn- och ungdomsmedicinska kliniken
Länssjukhuset Ryhov
Jönköping
551 85
Sweden
+46 (0)10 241 00 00
johan.gyllensvard@rjl.se

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

dnr 2018/503-31

Study information

Scientific title

C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay

Acronym

Study hypothesis

It is hypothesized that the implementation of the new treatment guidelines would lead to reduced antibiotic use, hospital stay and healthcare costs, with no reinfection in a cohort of term infants.

Ethics approval

Approved 11/11/2018, The regional ethical committee of Linköping (Etikprövningsmyndigheten, Box 2110, 750 02 Uppsala Sweden; +46 (0)10 4750808; registrator@etikprovning.se), ref: dnr 2018/503-31

Study design

Single-centre before and after interventional study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Early-onset sepsis in term neonates

Intervention

The intervention includes new treatment guidelines introduced on 11 June 2018. The researchers decided a priori to evaluate the guidelines by comparing data from 24 months before and 15-16 months after the introduction of the guidelines after they did a sample size calculation. Period 1 was between 1 January 2016 and 31 December 2017 and period 2 was between 11 June 2018 and 30 September 2019. Infants born during period 1 were considered a control group. The guidelines include C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. According to the new treatment guidelines, the intravenous antibiotic therapy (benzylpenicillin 50 mg/kg every 8-12 h and amikacin 15 mg/kg every 24 h) can be withdrawn after three days followed by administration of oral suspension antibiotic (amoxicillin, 20 mg/kg three times a day) for two more days in term neonates meeting the criteria of the new treatment guidelines.

The new guidelines contain the following criteria:
1. Term neonate (week 37 + 0 to week 41 + 6)
2. No need for intensive care (including invasive respiratory support or cardiovascular support) initially when the antibiotic treatment started
3. The neonate appeared well on day 3
4. The blood culture was not positive on day 3
5. Maximum CRP value of 80 mg/l decreasing by at least 50% during the first 3 days

Before the new guidelines were introduced, neonates with both culture-positive and culture-negative early-onset sepsis used to be treated with at least seven days of intravenous antibiotics at the neonatal intensive care unit.

Intervention type

Drug

Phase

Not Applicable

Drug names

Amoxicillin, amikacin, benzylpenicillin

Primary outcome measure

The number of days with antibiotic treatment, collected retrospectively from medical records for Period 1 between 1 January 2016 and 31 December 2017 and period 2 between 11 June 2018 and 30 September 2019

Secondary outcome measures

1. Reinfection or readmission to hospital within 3 days after completed antibiotic treatment
2. Hospital stay
3. Healthcare costs calculated based on the cost per day of care
Data collected retrospectively from medical records for Period 1 between 1 January 2016 and 31 December 2017 and period 2 between 11 June 2018 and 30 September 2019

Overall trial start date

19/02/2018

Overall trial end date

19/05/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Term neonates in gestational week 37 + 0 to week 41 + 6
2. Clinically diagnosed as early-onset sepsis that had initiated antibiotic treatment within 72 h of life

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

There were 7618 term infants (week 37 + 0 to week 41 + 6) who were born before and 5005 term infants born after the introduction of the new guidelines. 237 patients had early-onset sepsis during the study period (140 before and 97 neonates after the introduction of the guidelines).

Total final enrolment

237

Participant exclusion criteria

Term neonates who received prophylactic antibiotic treatment and not because of early-onset sepsis

Recruitment start date

01/01/2016

Recruitment end date

30/09/2019

Locations

Countries of recruitment

Sweden

Trial participating centre

Ryhov Hospital
Barn- och ungdomsmedicinska kliniken Länssjukhuset Ryhov
Jönköping
553 05
Sweden

Sponsor information

Organisation

Ryhov County Hospital

Sponsor details

Barn- och ungdomsmedicinska kliniken
Länssjukhuset Ryhov
Jönköping
55185
Sweden
+46 (0)10 241 00 00
johan.gyllensvard@rjl.se

Sponsor type

Hospital/treatment centre

Website

https://www.rjl.se/lanssjukhusetryhov

Funders

Funder type

Hospital/treatment centre

Funder name

Ryhov County Hospital

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Futurum - the academy for healthcare, Region Jönköping County

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

1. There is a study protocol in Swedish which is available upon request
2. Results from the study will be published in a peer-reviewed scientific journal

IPD sharing statement
The datasets generated and/or analysed during the current study are not publicly available due to the ethics committee specifically stating that no data which can identify a patient can be publicly available but are available from the corresponding author Johan Gyllensvärd (johan.gyllensvard@rjl.se) on reasonable request.

Intention to publish date

22/06/2019

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

28/05/2020: Trial's existence confirmed by the regional ethical committee of Linköping.