Use of Presepsin as a Marker for Immunotherapy Administration in Pneumonia

NCT05785442 | Completed Phase 2

• 2 other identifiers: INSPIRE2022-002390-28
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

The current study is an exploratory, phase IIa randomized clinical trial (RCT) aiming to evaluate if early presepsin increase coupled with early initiation of anakinra as an adjunct therapy to the standard-of-care treatment may improve outcomes of community-acquired pneumonia or hospital-acquired pneumonia.

Conditions

Community-acquired Pneumonia; Hospital-acquired Pneumonia

Keywords

sepsis; presepsin; pneumonia; anakinra; SOFA

Outcome Measures

Primary Outcomes (1)

• Change of Sequential Organ Failure Assessment score by day 7 or death by day 90.

  Patients who meet any of the following are considered to meet this endpoint: i) increase of Sequential Organ Failure Assessment score by 2 or more points from day 1 (before start of the study drug) until day 7; ii) death by day 90. Higher scores of the Sequential Organ Failure Assessment score indicate worsening of organ function, where the lowest score is 0 and highest is 24 (death).

  90 days

Secondary Outcomes (11)

• Change of Sequential Organ Failure Assessment score

  28 days

• 28-day organ dysfunction

  28 days

• Time to hospital discharge

  28 days

• 28-day mortality

  28 days

• 90-day mortality

  90 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Treatment Arm 1: patients receiving placebo (N/S 0.9% w/v) subcutaneously once daily for 10 days plus Standard of Care

Drug: Placebo

Anakinra

ACTIVE COMPARATOR

Treatment Arm 2: patients receiving anakinra subcutaneously 100 mg once daily for 10 days plus Standard of Care

Drug: Anakinra Prefilled Syringe

Interventions

Anakinra Prefilled Syringe DRUG

Anakinra 100 mg administration subcutaneously once daily for 10 days (at least 4 days)

Also known as: Kineret

Anakinra

Placebo DRUG

0.67 ml N/S 0.9% w/v administration subcutaneously once daily for 10 days (at least 4 days)

Also known as: NaCl

Placebo

Eligibility Criteria

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

You may qualify if:

• Age equal to or above 18 years
• Male or female gender
• In case of women of reproductive age, willingness to use dual contraceptive method during the study period
• Written informed consent provided by the patient. For subjects without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation in the Member State where the trial is planned
• Community-acquired pneumonia or hospital-acquired pneumonia
• qSOFA score equal to 1
• Serum presepsin \> 350 pg/ml

You may not qualify if:

• Age below 18 years
• Denial of written informed consent
• Any stage IV malignancy
• Any do not resuscitate decision
• Patients with PaO2/FiO2 less than 150 necessitating non-invasive ventilation or mechanical ventilation
• Hospitalization in Intensive Care Unit
• Known hypersensitivity to anakinra
• Oral or IV intake of corticosteroids at a daily dose equal to or greater than 0.4 mg/kg prednisone for a period greater than the last 15 days
• qSOFA score 0, 2 or 3
• Any anti-cytokine biological treatment for the last one month
• Participation in any other interventional trial

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (5)

4th Department of Internal Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School

Athens, 12462, Greece

Location

1st Department of Internal Medicine, General Hospital of Athens GENNIMATAS

Athens, Greece

Location

1st Department of Internal Medicine, General Hospital of Eleusis THRIASIO

Athens, Greece

Location

6th Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens

Athens, Greece

Location

3rd Department of Internal Medicine, General Hospital of Nikaia AGIOS PANTELEIMON

Nikaia, Greece

Location

Related Publications (1)

• Tavoulareas G, Kontakou-Zoniou O, Antonakos N, Tasouli E, Adamis G, Kakavoulis N, Michelakis E, Skopelitis I, Dakou K, Psarrakis C, Koufargyris P, Astriti M, Sympardi S, Giamarellos-Bourboulis EJ. Efficacy of anakinra in reducing progression to organ dysfunction in patients with pneumonia (INSPIRE): a randomised, double-blind, placebo-controlled, phase IIa trial. Lancet Reg Health Eur. 2025 Dec 29;62:101573. doi: 10.1016/j.lanepe.2025.101573. eCollection 2026 Mar.

  PMID: 41552367 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia; Healthcare-Associated Pneumonia; Sepsis; Pneumonia

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Cross Infection; Lung Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Evangelos Giamarellos-Bourboulis, MD, PhD

  Hellenic Institute for the Study of Sepsis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is designed to maintain blinding from participants, site investigators and their teams until completion of the study. At each center, there will be an unblinded pharmacist (and one substitute) who will be in charge of randomizing and preparing the study drug for each participant according to the randomized intervention assignment. These pharmacists will not be involved in data acquisition, collection, adjudication of outcomes or adverse events, or any other study procedures. They will not disclose the treatment assignment to the study team members unless it is via a formal process of early unblinding as described below. Αn independent biostatistician will generate the assignment to blinding treatment. Under normal circumstances, all the treatment assignments of participants will remain blinded until the completion of the trial (completion of enrollment and follow-up or early termination of the trial).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 27, 2023
• Study Start: March 6, 2023
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: July 31, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GR (5)