Efficacy of Pancreatic Stone Protein-Guided Early Meropenem Administration to Mitigate Sepsis Risk in Patients Presenting to the Emergency Department: A Phase III RCT
- Trial ID
- 2025-525006-37-00
- Protocol
- PROMISE
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate whether a single dose of meropenem improves clinical outcomes in patients with suspected infection at risk of mortality. Treatment is guided by the presence of a single qSOFA score indicator or a NEWS2 score of 5 or 6 in conjunction with blood pancreatic stone protein levels ≥300 ng/ml. This intervention aims to mitigate the risk of sepsis within the emergency department setting.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of adults of both sexes experiencing suspected infection. Inclusion requires the presence of clinical signs such as fever, tachycardia, shortness of breath, dysuria, diarrhea, or abdominal pain. Additionally, participants must present either one sign of the qSOFA score or a NEWS2 score of 5 or 6 in conjunction with a blood procalcitonin level of ≥300 ng/ml. The population includes vulnerable individuals.
Plans and Procedures
This Phase III, randomized, double-blind, controlled clinical trial is designed to evaluate the efficacy of early intervention with a single dose of meropenem in patients with suspected infection at risk of sepsis. The study methodology involves guiding treatment based on the presence of one qSOFA sign or a NEWS2 score of 5 or 6, in conjunction with blood pancreatic stone protein levels greater than or equal to 300 ng/ml. Participants are randomized to receive either the test product via intravenous infusion or a sodium chloride placebo. The primary objective is to assess 28-day mortality. Secondary endpoints include progression into organ dysfunction, changes in SOFA-2 scores, 90-day mortality, and rates of hospitalization. The trial is expected to occur between June 2026 and June 2028.
Treatment
The experimental treatment consists of meropenem (as meropenem anhydrous) administered as a solution for injection/infusion. The dosage is 2 g, delivered via intravenous infusion.
The control group receives a placebo consisting of sodium chloride 0.9%. This is provided as a 100 ml solution for infusion for intravenous infusion.
Efficacy
The primary efficacy endpoint is 28-day mortality, which is defined as death from any cause occurring within 28 days following randomization. Survival is censored at day 28 to assess the impact of early meropenem administration guided by early sepsis detection.
Secondary endpoints include:
- Progression into organ dysfunction, defined as an increase in the total SOFA-2 score by 2 or more points within the first 24 hours.
- Comparative changes in total SOFA-2 scores by 48 and 96 hours.
- Time to stop of antibiotics, determined by the discretion of attending physicians.
- Rate of hospitalization.
- Time to hospital discharge alive.
- 90-day mortality.
- Kinetics of pancreatic stone protein (PSP) over time and per type of infection.
- Rate of resistant fecal flora.
- Re-evaluation of primary and secondary endpoints for patients classified into infections after adjudication.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent
- Adult (≥ 18 years) patients of both sexes.
- Suspicion of infection defined as the presence of at least one of: Fever defined as core temperature ≥380 C , Tachycardia defined as more than 90 heart beats/min ,Acute presence of any of: shortness of breath or dysuria, or diarrhea or abdominal pain,Complaints that according to investigator’s discretion indicate/are correlated with the presence of infection
- Presence of either a) one of qSOFA signs (mental confusion, systolic blood pressure less than 100mmHg, respiratory rate more than 22 breaths/min) OR b) NEWS2 equal to 5 or 6 (see Appendices I and II). It is explicitly stated that patients with 0 qSOFA signs may be enrolled in the study if the NEWS2 is 5 or 6. It is also explicitly stated that patients with NEWS2 less than 5 may be enrolled in the study if qSOFA is equal to one.
- PSP ≥300ng/ml
Exclusion Criteria
- Deny to consent
- Age less than 18 years
- Patients with nil signs of qSOFA
- Patients with two or three qSOFA signs
- Pregnancy (confirmed by blood or urinary pregnancy test that will be conducted after the signing of the consent form at the emergency department) for female patients of reproductive age or lactation
- NEWS2 ≥ 7
- Full-blown sepsis with overt organ dysfunction (defined as need of high flow oxygen or mechanical ventilation or vasopressors)
- Hypersensitivity to meropenem, or to any other antibacterial agent that includes meropenem. Severe hypersensitivity to any antibacterial agent belonging to beta lactam class (eg. penicillins or cephalosporins).
- Patients receiving probenecid, valproic acid or warfarin.
- Documented acute organ dysfunction compatible with sepsis, as reflected by an increase in SOFA-2 score by ≥2 points.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Yet Recruiting | 01 Jun 2026 | 398 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Meronem 1g κόνις για ενέσιμο διάλυμα ή διάλυμα προς έγχυση | Test | ΚΌΝΙΣ ΓΙΑ ΕΝΈΣΙμΟ ΔΙΆΛΥμΑ Ή ΔΙΆΛΥμΑ ΠΡΟΣ ΈΓΧΥΣΗ | INTRAVENOUS INFUSION | 2 | 1 | PRD12355716 |
Sodium Chloride 0,9% | Placebo | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 100 | 1 | PRD355844 |