Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

26 Jun 2025 → ongoing

Decision date (initial)

2024-04-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509703-33-00

WHO UTN

U1111-1301-6379

ClinicalTrials.gov

NCT06184659

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the effects of empirical meropenem versus piperacillin/tazobactam on mortality and other patient-important outcomes in critically ill adults with sepsis.

Conditions and MedDRA coding

Septic Shock

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥ 18 years
2. 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)
3. Critical illness defined as use of at least one of the following: a. Invasive 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)
4. Clinical indication for empirical treatment with either meropenem or piperacillin/tazobactam

Exclusion criteria 10

1. Preceding intravenous treatment with meropenem or piperacillin/tazobactam for > 24 hours prior to screening
2. Fertile women < 60 years of age with known pregnancy or positive urine human gonadotropin (hCG) or plasma hCG
3. Known hypersensitivity or allergy to beta-lactam antibiotics
4. Suspected or documented central nervous system infection
5. 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)
6. Current or planned use of valproate within 30 days from randomisation
7. Patient included in another interventional trial where co-enrolment with EMPRESS is not permitted
8. Previously randomised into the EMPRESS trial
9. Informed consent following inclusion expected to be unobtainable
10. Patient under coercive measures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. All-cause mortality at day 30 after randomisation

Secondary endpoints 10

1. 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
2. Number of participants with new isolation precautions due to one or more resistant bacteria within 30 days of randomisation
3. 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
4. Days alive and out of hospital from randomisation to day 30
5. 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
6. Days alive and out of hospital from randomisation to day 90
7. All-cause mortality at day 90
8. All-cause mortality at day 180
9. HRQoL at day 180 using EQ-5D-5L index values
10. HRQoL at day 180 using EQ VAS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Morten Hylander Møller

Public contact point

Organisation

Rigshospitalet

Contact name

Nick Meier

Third parties 1

Locations

2 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications