Meropenem versus piperacillin/tazobactam for adults with sepsis
Empirical Meropenem Versus Piperacillin/Tazobactam for Adult Patients With Sepsis (EMPRESS) Trial
This trial will test whether meropenem or piperacillin/tazobactam works better and safer as the first antibiotic for critically ill adults with sepsis.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 5800 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Scandinavian Critical Care Trials Group Academic / other |
| Locations | 2 sites (Copenhagen, København Ø and 1 other locations) |
| Trial ID | NCT06184659 on ClinicalTrials.gov |
What this trial studies
EMPRESS is an international, investigator-initiated, randomized, open-label adaptive trial comparing empirical meropenem with piperacillin/tazobactam in critically ill adults meeting Sepsis-3 criteria. It uses response-adaptive randomisation and adaptive stopping rules with an integrated feasibility phase to make the trial more likely to reach clear conclusions and to increase patients' chances of receiving the better-performing antibiotic. The primary focus is on mortality and other patient-important outcomes during critical care, with participants enrolled when clinicians plan empirical treatment with either study antibiotic. The trial excludes patients who have already received these antibiotics intravenously for more than 24 hours and other standard contraindications.
Who should consider this trial
Good fit: Adults (≥18 years) who are critically ill with sepsis or septic shock by Sepsis-3 criteria, require intensive support such as mechanical ventilation, high-flow oxygen/CPAP, or continuous vasopressors, and for whom clinicians intend empirical treatment with meropenem or piperacillin/tazobactam are ideal candidates.
Not a fit: Patients who have already had more than 24 hours of intravenous meropenem or piperacillin/tazobactam, pregnant women or those with contraindications to either drug, and less severely ill patients not requiring intensive organ support are unlikely to benefit from participating.
Why it matters
Potential benefit: If successful, the trial could identify which antibiotic reduces deaths and complications in critically ill sepsis patients and guide safer initial antibiotic choices.
How similar studies have performed: Previous systematic reviews suggested possible worse outcomes with piperacillin/tazobactam in severe infections but the evidence was low or very low certainty, so conclusive comparisons are still lacking.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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: 1. Invasive mechanical ventilation 2. Non-invasive ventilation 3. Continuous use of continuous positive airway pressure (CPAP) for hypoxia 4. Oxygen supplementation with an oxygen flow of ≥ 10 litres (L)/minute independent of delivery system and total flows 5. Continuous infusion of any vasopressor or inotrope (excluding strictly procedure-related infusions) * Clinical indication for empirical treatment with either meropenem or piperacillin/tazobactam Exclusion Criteria: * 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 * Informed consent following inclusion expected to be unobtainable * Patient under coercive measures
Where this trial is running
Copenhagen, København Ø and 1 other locations
- Rigshospitalet — Copenhagen, København Ø, Denmark (Not_yet_recruiting)
- Rigshospitalet — Copenhagen, Denmark (Recruiting)
Study contacts
- Study coordinator: Morten H Møller, MD, Professor, PhD
- Email: morten.hylander.moeller@regionh.dk
- Phone: 4535458685
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.