Clinical trial • Infectious Disease

LINEZOLID for Sepsis | Septic shock

Clinical trial of LINEZOLID for Sepsis | Septic shock.

Overview

Trial Therapeutic Area
Infectious Disease
Trial Disease
Sepsis | Septic shock
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
20-12-2023
First CTIS Authorization Date
10-04-2024

Trial design

Randomised, piperacillin and beta-lactamase inhibitor (piperacillin sodium, tazobactam sodium), intravenous administration; max daily dose amount listed as 24 g (product entry: maxdailydoseamount: 24 g).-controlled trial in Denmark, Sweden.

Randomised
Yes
Comparator
PIPERACILLIN AND BETA-LACTAMASE INHIBITOR (piperacillin sodium, tazobactam sodium), intravenous administration; max daily dose amount listed as 24 g (product entry: maxDailyDoseAmount: 24 g).
Target Sample Size
700
Trial Duration For Participant
180

Eligibility

Recruits 700 The trial has vulnerable population selected (isVulnerablePopulationSelected: true). Patients under coercive measures are explicitly excluded and subjects for whom informed consent following inclusion is expected to be unobtainable are excluded. Subject information and informed consent forms include versions for guardian and relative (documents: L1_ICF_Guardian, L1_ICF_Relative) and other subject information materials are listed among documents..

Pregnancy Exclusion
Fertile women < 60 years of age with known pregnancy or positive urine human gonadotropin (hCG) or plasma hCG
Vulnerable Population
The trial has vulnerable population selected (isVulnerablePopulationSelected: true). Patients under coercive measures are explicitly excluded and subjects for whom informed consent following inclusion is expected to be unobtainable are excluded. Subject information and informed consent forms include versions for guardian and relative (documents: L1_ICF_Guardian, L1_ICF_Relative) and other subject information materials are listed among documents.

Inclusion criteria

  • {"criterion_text":"- Age ≥ 18 years"}
  • {"criterion_text":"- Sepsis (including septic shock) defined according to the Sepsis-3 criteria, i.e., suspected or documented infection and an acute increase of ≥ 2 points in the Sequential Organ Failure Assessment (SOFA) score (a marker of acute organ dysfunction)"}
  • {"criterion_text":"- Critical illness defined as use of at least one of the following: a.\tInvasive mechanical ventilation b. Non-invasive ventilation c. Continuous use of continuous positive airway pressure (CPAP) for hypoxia d. Oxygen supplementation with an oxygen flow of ≥ 10 litres (L)/minute independent of delivery system and total flows e. Continuous infusion of any vasopressor or inotrope (excluding strictly procedure-related infusions)"}
  • {"criterion_text":"- Clinical indication for empirical treatment with either meropenem or piperacillin/tazobactam"}

Exclusion criteria

  • {"criterion_text":"- Preceding intravenous treatment with meropenem or piperacillin/tazobactam for > 24 hours prior to screening"}
  • {"criterion_text":"- Patient under coercive measures"}
  • {"criterion_text":"- Fertile women < 60 years of age with known pregnancy or positive urine human gonadotropin (hCG) or plasma hCG"}
  • {"criterion_text":"- Known hypersensitivity or allergy to beta-lactam antibiotics"}
  • {"criterion_text":"- Suspected or documented central nervous system infection"}
  • {"criterion_text":"- Known infection/colonialization with microorganism with acquired resistance against meropenem or piperacillin/tazobactam within the previous 3 months (e.g., ESBL-, AmpC- or carbapenemase-producing bacteria)"}
  • {"criterion_text":"- Current or planned use of valproate within 30 days from randomisation"}
  • {"criterion_text":"- Patient included in another interventional trial where co-enrolment with EMPRESS is not permitted"}
  • {"criterion_text":"- Previously randomised into the EMPRESS trial"}
  • {"criterion_text":"- Informed consent following inclusion expected to be unobtainable"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- All-cause mortality at day 30 after randomisation","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Number of participants with one or more serious adverse reactions (SARs, defined as anaphylactic shock to IV piperacillin/tazobactam or meropenem, invasive fungal infection, pseudomembranous colitis, or toxic epidermal necrolysis) within 30 days of randomisation","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of participants with new isolation precautions due to one or more resistant bacteria within 30 days of randomisation","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Days alive without life support (i.e., invasive mechanical ventilation, circulatory support, or renal replacement therapy [including days in between intermittent renal replacement therapy]) from randomisation to day 30","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Days alive and out of hospital from randomisation to day 30","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Days alive without life support (i.e., invasive mechanical ventilation, circulatory support, or renal replacement therapy [including days in between intermittent renal replacement therapy]) from randomisation to day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Days alive and out of hospital from randomisation to day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- All-cause mortality at day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- All-cause mortality at day 180","definition_or_measurement_approach":""}
  • {"endpoint_text":"- HRQoL at day 180 using EQ-5D-5L index values","definition_or_measurement_approach":""}
  • {"endpoint_text":"- HRQoL at day 180 using EQ VAS","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
700
Recruitment Window Months
51
Consent Approach
Informed consent and subject information documents are provided (documents listed include L1_ICF EMPRESS, L1_SIS, L1_ICF_Guardian, L1_ICF_Relative, L1_GIS, L1_RIS and other subject information materials). Participants will be informed about data sharing during the informed consent process (stated in individualParticipantData). Exclusion criteria note participants for whom informed consent following inclusion is expected to be unobtainable are excluded. Guardian and relative informed consent forms are available according to document list.

Geography

Total Number Of Sites
29
Total Number Of Participants
700

Denmark

Earliest CTIS Part Ii Submission Date
23-03-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
755
Number Of Sites
25
Number Of Participants
400

Sites

Site Name
Bispebjerg Hospital
Department Name
Department of Intensive Care
Contact Person Name
Nanna Reiter
Contact Person Email
nanna.reiter@regionh.dk
Site Name
Region Midtjylland
Department Name
Department of Intensive Care
Contact Person Name
Helle Bundgaard
Contact Person Email
helle.bundgaard@randers.rm.dk
Site Name
Herlev Hospital
Department Name
Department of Intensive Care
Contact Person Name
Anne Sofie Andreasen
Site Name
Region Midtjylland
Department Name
Department of Intensive Care, North
Contact Person Name
Klaus Ulrik Koch
Contact Person Email
klaukoch@rm.dk
Site Name
Kolding Sygehus
Department Name
Department of Intensive Care
Contact Person Name
Anne Brøchner
Site Name
Hillerod Hospital
Department Name
Department of Intensive Care
Contact Person Name
Morten Bestle
Contact Person Email
morten.bestle@regionh.dk
Site Name
Regionshospital Nordjylland
Department Name
Department of Intensive Care
Contact Person Name
Malgorzata B Pawlowicz-Dworzanska
Contact Person Email
mabep@rn.dk
Site Name
Odense University Hospital
Department Name
Department of infectious diseases
Contact Person Name
Isik Johansen
Contact Person Email
empress@cric.nu
Site Name
Region Sjaelland
Department Name
Department of intensive care
Contact Person Name
Lars Peter Kloster Andersen
Contact Person Email
lpka@regionsjaelland.dk
Site Name
Nykoebing F Sygehus
Department Name
Department of Intensive Care, 4131
Contact Person Name
Hans Fjeldsøe-Nielsen
Contact Person Email
nf-sygehus@regionsjaelland.dk
Site Name
Hvidovre Hospital
Department Name
Department of infectious diseases
Contact Person Name
Thomas Benfield
Contact Person Email
empress@cric.nu
Site Name
Esbjerg Og Grindsted Sygehus
Department Name
Department of intensive care
Contact Person Name
Henrik Nørlund
Contact Person Email
svs-forskning@rsyd.dk
Site Name
Slagelse Hospital
Department Name
Department of Intensive Care
Contact Person Name
Anne Groenborg Vedel
Contact Person Email
agse@regionsjaelland.dk
Site Name
Region Midtjylland
Department Name
Department of Intensive Care
Contact Person Name
Thomas Tværmose Troelsen
Contact Person Email
thomtroe@rm.dk
Site Name
Hvidovre Hospital
Department Name
Department of Intensive Care
Contact Person Name
Ronni Plovsing
Site Name
Rigshospitalet
Department Name
Department of Neuroanaesthesiology
Contact Person Name
Kirsten Møller
Contact Person Email
kirsten.moeller.01@regionh.dk
Site Name
Rigshospitalet
Department Name
Department of Cardiology B
Contact Person Name
Christian Hasseager
Contact Person Email
christian.hassager@regionh.dk
Site Name
Aalborg University Hospital
Department Name
Department of Intensive Care
Contact Person Name
Bodil Steen Rasmussen
Contact Person Email
bodil.steen.rasmussen@rn.dk
Site Name
Region Midtjylland
Department Name
Department of Intensive Care
Contact Person Name
Christoffer Sølling
Contact Person Email
chrsoell@rm.dk
Site Name
Rigshospitalet
Department Name
Department og Thoraxanaesthesiology
Contact Person Name
Theis Itenov
Contact Person Email
pbhjortrup@gmail.com
Site Name
Rigshospitalet
Department Name
Department of Intensive Care, 4131
Contact Person Name
Morten Hyllander
Site Name
Region Midtjylland
Department Name
Department of Intensive Care, East
Contact Person Name
Steffen Christensen
Contact Person Email
steffen.christensen@auh.rm.dk
Site Name
Holbaek Sygehus
Department Name
Department of Intensive Care
Contact Person Name
Mette Krag
Contact Person Email
mevo@regionsjaelland.dk
Site Name
Rigshospitalet
Department Name
Department of infectious diseases
Contact Person Name
Marie Helleberg
Contact Person Email
empress@cric.nu

Sweden

Earliest CTIS Part Ii Submission Date
05-12-2025
Latest Decision Or Authorization Date
29-01-2026
Processing Time Days
55
Number Of Sites
4
Number Of Participants
300

Sites

Site Name
Karolinska University Hospital
Department Name
Karolinska University Hospital Stockholm
Contact Person Name
Johan Petersson
Site Name
Region Joenkoepings Laen
Department Name
OP IVA Ryhov
Contact Person Name
Knut Taxbro
Contact Person Email
kliniskastudierfuturum@rjl.se
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Skane University Hospital, Malmö
Contact Person Name
Fredrik Sjövall
Contact Person Email
fredrik.sjovall@med.lu.se
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Skane University Hospital Lund
Contact Person Name
Anna Lybeck
Contact Person Email
empress@cric.nu

Sponsor

Primary sponsor

Full Name
Rigshospitalet
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Denmark

Third parties

  • {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
MEROPENEM
Active Substance
LINEZOLID
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENIOUS INFUSION
Maximum Dose
6 g
Investigational Product Name
PIPERACILLIN AND BETA-LACTAMASE INHIBITOR
Active Substance
PIPERACILLIN SODIUM, TAZOBACTAM SODIUM
Modality
Small molecule
Routes Of Administration
INTRAVENOUS ADMINISTRATION
Route
INTRAVENOUS ADMINISTRATION
Maximum Dose
24 g

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