NCT01988428

Brief Summary

Sepsis is one of the most frequent reasons for referral to emergency departments (EDs) worldwide. The incidence of sepsis is likely to rise in the upcoming years. Sepsis has a tendency to become more serious when left untreated with a high mortality rate, exceeding even those of myocardial infarction and stroke. Therefore, much effort has been put in to start with appropriate therapy as early as possible. Early goal-directed therapy (EGDT) in the emergency department with fluid resuscitation, administration of vasopressors/vasodilators and intravenous antibiotics in patients with severe sepsis and septic shock has indeed decreased mortality substantially. Emergency medical services (EMS) personnel have already made a significant difference in improving care for patients with acute coronary syndrome, multiple trauma and stroke. Patients with severe sepsis or septic shock could also benefit greatly from timely pre-hospital care. Earlier recognition and initiation of treatment by EMS personnel may improve survival even more. Interestingly, the first hour of ED presentation seems to be the most critical hour. Administration of antibiotics and fluid resuscitation in the pre-hospital setting will reduce the time to administration substantially. In adults, to the best of our knowledge, no studies on the effect of pre-hospital administration of antibiotics have been performed. In children with meningitis, some uncontrolled studies show contradictory results, most probably due to bias by severity. We propose a non-blinded randomised multicentre clinical trial study on the efficacy of early, pre-hospital intravenous administration of broad spectrum antibiotics (ceftriaxone), which are effective against a wide variety of infectious pathogens that cause most common community-acquired infections) in patients referred to the ED with suspected severe sepsis or septic shock. Objective: To evaluate whether early, pre-hospital administration of antibiotics, together with training of ambulance personnel in recognizing and initiating treatment reduces 28-day mortality in patients referred to the ED with suspected severe sepsis or septic shock Study design: Non-blinded randomized multicentre clinical trial nested within a stepped wedge design Study population: All patients above the age of 18 years, with suspected severe sepsis or septic shock and transferred to the ED by ambulance, are eligible for study inclusion Intervention: prehospital antibiotics (ceftriaxone 2000 mg intravenously) Main study parameters/endpoints: 28-day mortality, hospital length of stay, admission to intensive or medium care unit (ICU/MC), time to administration of antibiotics. Follow up of one year. QoL after one month after discharge.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,672

participants targeted

Target at P75+ for not_applicable sepsis

Timeline
Completed

Started Jun 2014

Typical duration for not_applicable sepsis

Geographic Reach
1 country

34 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2013

Completed
15 days until next milestone

First Posted

Study publicly available on registry

November 20, 2013

Completed
6 months until next milestone

Study Start

First participant enrolled

June 1, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2017

Completed
Last Updated

June 15, 2017

Status Verified

June 1, 2017

Enrollment Period

3 years

First QC Date

November 5, 2013

Last Update Submit

June 13, 2017

Conditions

Keywords

sepsissevere sepsisseptic shock

Outcome Measures

Primary Outcomes (1)

  • mortality

    To evaluate whether early, pre-hospital administration of antibiotics reduces 28-day mortality in patients referred to the ED with suspected severe sepsis or septic shock.

    28 day mortality

Secondary Outcomes (1)

  • length of stay

    an expected average of 5 weeks

Other Outcomes (3)

  • quality of life

    one month after discharge hospital

  • Length of stay at ICU

    Participants will be followed for the duration of ICU stay, an expected average of 5 weeks may vary from a few days to several weeks

  • time to adminstration of antibiotics (door to needle time)

    door to needle time at the ED: from entry at the ED till time to administration of antibiotics

Study Arms (2)

standard care

NO INTERVENTION

* standard care * training of ambulance personnel in recognizing sepsis and initiating pre-hospital treatment

Antibiotics

EXPERIMENTAL

* ceftriaxone 2000 mg (after taking bloodcultures) * training of ambulance personnel in recognizing sepsis and initiating pre-hospital treatment

Drug: Ceftriaxone 2000 mg

Interventions

Ceftriaxone 2000 mg

Also known as: rocephin (roche)
Antibiotics

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- All patients older than 18 years who are suspected of sepsis AND have an abnormal temperature (\>38 degrees Celsius or \< 36 degrees Celsius) in combination with at least one of the following two SIRS criteria, abnormal pulse (\> 90 beats per minute) and/or abnormal respiratory rate (\> 20 per minutes)

You may not qualify if:

  • Age \<18 years
  • Known severe allergic reaction to ceftriaxone or to other beta lactam antibiotics
  • Known pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (34)

Amstelland Ziekenhuis

Amstelveen, North Holland, 1186 AM, Netherlands

Location

Meander Medical Center

Amersfoort, Netherlands

Location

Academic Medical Centre

Amsterdam, Netherlands

Location

BovenIJ hospital

Amsterdam, Netherlands

Location

Onze Lieve Vrouwe Gasthuis Oost (former: St. Lucas Andreas Hospital)

Amsterdam, Netherlands

Location

Onze Lieve Vrouwe Gasthuis Oost

Amsterdam, Netherlands

Location

VU medical center

Amsterdam, Netherlands

Location

Rijnstate Hospital

Arnhem, Netherlands

Location

Rode Kruis Hospital

Beverwijk, Netherlands

Location

Amphia Hospital

Breda, Netherlands

Location

Albert Schweitzer Hospital

Dordrecht, Netherlands

Location

Gelderse Vallei

Ede, Netherlands

Location

Catharina Hospital

Eindhoven, Netherlands

Location

Maxima Medical Center

Eindhoven, Netherlands

Location

St.Anna Hospital

Geldrop, Netherlands

Location

Zuyderland Hospital

Geleen, Netherlands

Location

Beatrix Hospital

Gorinchem, Netherlands

Location

Spaarne Gasthuis, Haarlem

Haarlem, Netherlands

Location

Zuyderland Hospital

Heerlen, Netherlands

Location

Elkerliek Hospital

Helmond, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, Netherlands

Location

Maastricht Medical Center

Maastricht, Netherlands

Location

St.Antonius Hospital

Nieuwegein, Netherlands

Location

Canisius Wilhemina Hospital

Nijmegen, Netherlands

Location

Bravis Hospital

Roosendaal, Netherlands

Location

Haven Hospital

Rotterdam, Netherlands

Location

Ikazia Hospital

Rotterdam, Netherlands

Location

Maasstad Hospital

Rotterdam, Netherlands

Location

St.Franciscus Gasthuis

Rotterdam, Netherlands

Location

Vlietland Hospital

Schiedam, Netherlands

Location

Rivierenland Hospital

Tiel, Netherlands

Location

Diakonesse Hospital

Utrecht, Netherlands

Location

University Medical Center, Utrecht

Utrecht, Netherlands

Location

VieCuri Medical Center

Venlo, Netherlands

Location

Related Publications (3)

  • Ling L, Joynt GM, Lipman J. A narrative review on antimicrobial therapy in septic shock: updates and controversies. Curr Opin Anaesthesiol. 2021 Apr 1;34(2):92-98. doi: 10.1097/ACO.0000000000000954.

  • Nannan Panday RS, Lammers EMJ, Alam N, Nanayakkara PWB. An overview of positive cultures and clinical outcomes in septic patients: a sub-analysis of the Prehospital Antibiotics Against Sepsis (PHANTASi) trial. Crit Care. 2019 May 21;23(1):182. doi: 10.1186/s13054-019-2431-8.

  • Alam N, Oskam E, Stassen PM, Exter PV, van de Ven PM, Haak HR, Holleman F, Zanten AV, Leeuwen-Nguyen HV, Bon V, Duineveld BAM, Nannan Panday RS, Kramer MHH, Nanayakkara PWB; PHANTASi Trial Investigators and the ORCA (Onderzoeks Consortium Acute Geneeskunde) Research Consortium the Netherlands. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018 Jan;6(1):40-50. doi: 10.1016/S2213-2600(17)30469-1. Epub 2017 Nov 28.

MeSH Terms

Conditions

SepsisShock, Septic

Interventions

Ceftriaxone

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

CefotaximeCephacetrileCephalosporinsbeta-LactamsLactamsAmidesOrganic ChemicalsThiazinesSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Prabath WB Nanayakkara, MD, PhD

    VU Medical Center (VUmc), Amsterdam

    PRINCIPAL INVESTIGATOR
  • P. Stassen, MD, Phd

    Maastricht Medical Center, Maastricht

    PRINCIPAL INVESTIGATOR
  • E. Oskam, MD

    Albert Schweitzer Hospital, Dordrecht

    PRINCIPAL INVESTIGATOR
  • H. Nguyen, MD, PhD

    Maasstad Hospital, Rotterdam

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
Open label
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Doctor

Study Record Dates

First Submitted

November 5, 2013

First Posted

November 20, 2013

Study Start

June 1, 2014

Primary Completion

June 1, 2017

Study Completion

June 1, 2017

Last Updated

June 15, 2017

Record last verified: 2017-06

Data Sharing

IPD Sharing
Will not share

Locations