Empirical Meropenem Versus Piperacillin/Tazobactam for Adult Patients With Sepsis

NCT06184659 | Recruiting Phase 4 DMC

• 2 other identifiers: RH-ITA-0102023-509703-33-00
• Study Type: interventional
• Target: 5,800
• Locations: 1 country
• Sites: 2

Brief Summary

The EMPRESS trial aims to test the two most commonly used antibiotics (meropenem and piperacillin/tazobactam) among intensive care patients with sepsis (blood poisoning), as the safety of these two drugs is unclear in this group of patients.

Conditions

Sepsis; Septic Shock

Keywords

Sepsis; Septic Shock; Intensive Care; Antimicrobial therapy; Meropenem; Piperacillin/Tazobactam

Outcome Measures

Primary Outcomes (1)

• All-cause mortality

  Number of participant deaths from all causes at day 30 after randomisation.

  Baseline to 30 days after enrollment

Secondary Outcomes (6)

• Serious Adverse Reaction (SAR)

  Baseline to 30 days after enrollment

• Bacterial resistance

  Baseline to 30 days after enrollment

• Days alive without life support

  Baseline to day 30 and day 90 after enrollment

• Days alive and out of hospital

  Day 30 and day 90 after enrollment

• All-cause mortality

  Day 90 and day 180 after enrollment

Study Arms (2)

Meropenem

EXPERIMENTAL

Participants in the experimental intervention arm will receive 1 g of IV meropenem three times daily administered according to usual clinical practice (i.e., intermittent-, prolonged-, or continuous infusion) until discharge from the participating site, death, or termination of empirical antibiotic therapy (including initiation of definitive treatment).

Drug: Meropenem

Piperacillin/Tazobactam

ACTIVE COMPARATOR

Participants in the control arm will receive 4/0.5 g of intravenous piperacillin/tazobactam four times daily administered according to usual clinical practice (i.e., intermittent-, prolonged-, or continuous infusion) until discharge from the participating site, death, or termination of empirical antibiotic therapy (including initiation of definitive treatment).

Drug: Piperacillin/Tazobactam

Interventions

Meropenem DRUG

For meropenem, the standard dose is 1 g administered 3 times daily as a 30-minute intravenous (IV) infusion, and the high dose is 2 g administered 3 times daily by extended 3-hour infusion

Meropenem

Piperacillin/Tazobactam DRUG

Standard dose of piperacillin/tazobactam 4/0.5 g administered 4 times daily as a 30-minute intravenous (IV) infusion or 3 times daily by extended 4-hour infusions and the recommended high dose is 4/0.5 g administered 4 times daily by extended 3-hour infusion

Piperacillin/Tazobactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Sepsis (including septic shock) defined according to the Sepsis-3 criteria (1), 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)
• Critical illness defined as use of at least one of the following:
• Invasive mechanical ventilation
• Non-invasive ventilation
• Continuous use of continuous positive airway pressure (CPAP) for hypoxia
• Oxygen supplementation with an oxygen flow of ≥ 10 litres (L)/minute independent of delivery system and total flows
• Continuous infusion of any vasopressor or inotrope (excluding strictly procedure-related infusions)
• Clinical indication for empirical treatment with either meropenem or piperacillin/tazobactam

You may not qualify if:

• Preceding intravenous treatment with meropenem or piperacillin/tazobactam for \> 24 hours prior to screening
• Fertile women \< 60 years of age with known pregnancy or positive urine human gonadotropin (hCG) or plasma hCG
• Known hypersensitivity or allergy to beta-lactam antibiotics
• Suspected or documented central nervous system infection
• 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)
• Current or planned use of valproate within 30 days from randomisation
• Patient included in another interventional trial where co-enrolment with EMPRESS is not permitted
• Previously randomised into the EMPRESS trial
• Patient under coercive measures

Sponsors & Collaborators

• Scandinavian Critical Care Trials Group: lead

Study Sites (2)

Rigshospitalet

Copenhagen, København Ø, 2100, Denmark

NOT YET RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Meropenem; Piperacillin, Tazobactam Drug Combination

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tazobactam; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Drug Combinations; Pharmaceutical Preparations

Central Study Contacts

Morten H Møller, MD, Professor, PhD

CONTACT

4535458685; morten.hylander.moeller@regionh.dk

Nick Meier, MD

CONTACT

4535450606; nick.meier@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: December 28, 2023
• Study Start: June 26, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): March 30, 2029
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

DK (2)