CLARITHROMYCIN TO PREVENT SECONDARY INFECTIONS IN PATIENTS WITH SEPSIS FOLLOWING LOWER RESPIRATORY TRACT INFECTIONS: THE CLASSIFY TRIAL

NCT07834346 | Recruiting Phase 3 DMC

• 3 other identifiers: CLASSIFY2025-525058-20-002025
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 19

Brief Summary

The goal of this clinical trial is to assess whether clarithromycin, given as an adjunct to standard-of-care antibiotic therapy, can reduce the risk of new infections and secondary sepsis in adult patients hospitalized with community-acquired pneumonia (CAP), sepsis, and sepsis-induced immunoparalysis (SII). The primary objective is to evaluate the effect of clarithromycin on the incidence of new infection, including worsening or recurrence of the initial CAP episode, new infections at other sites, and secondary sepsis during the 28-day follow-up period. Secondary objectives are to investigate the impact of clarithromycin on mortality, sepsis response, type of secondary infection, time to antimicrobial escalation, hospital readmission, quality of life, cost-effectiveness, and biomarkers of sepsis-induced immunoparalysis. Researchers will compare clarithromycin plus standard-of-care antibiotic therapy to placebo plus standard-of-care antibiotic therapy. Participants will:

• Receive clarithromycin or placebo, administered orally or intravenously, in addition to standard-of-care antibiotic therapy for up to 7 days.
• Be evaluated during treatment and follow-up through Day 28, with additional assessment of mortality, hospital readmission, and health status through Day 90.

Conditions

Sepsis

Keywords

sepsis; clarithromycin; CLASSIFY; CAP; Community Acquired Pneumonia; SOFA-1; SOFA-2; SII

Outcome Measures

Primary Outcomes (1)

• Incidence of new infection

  The incidence of new infection within 28 days following randomization, comparing intravenous or oral clarithromycin plus standard-of-care (SoC) antibiotic therapy with placebo plus SoC. The composite endpoint includes any of the following: * Worsening of the CAP episode, defined as the need to change SoC antibiotic treatment during the first 7 days. A change to moxifloxacin due to detection of atypical pathogens is not considered worsening. * Recurrence of CAP symptoms after initial improvement, requiring initiation of new treatment or a change in treatment after Day 7. * Any new infection at a non-pulmonary site during the first 28 days. * Secondary sepsis occurring between Day 8 and Day 28, defined as the onset of a new infection or recurrence of the CAP episode accompanied by an increase of at least 2 points in the total SOFA-1 score compared with the SOFA-1 score immediately before the new infection or CAP recurrence.

  Day 1 through Day 28.

Secondary Outcomes (12)

• All-cause mortality at Day 28

  Day 28.

• All-cause mortality at Day 90

  Day 90.

• Sepsis response at Day 7

  Day 7.

• Type of new sepsis episode

  Through Day 28.

• Each of the elements of the composite primary endpoint separately

  Through Day 28.

Other Outcomes (2)

• Sepsis response by SOFA-2

  Day 7.

• Primary endpoint according to baseline IL-6 and IFN-γ levels

  Through Day 28.

Study Arms (2)

Standard-of-care (SoC) and placebo

PLACEBO COMPARATOR

In the case of IV placebo medication, patients receive water for injection at a volume of 10ml diluted to a final volume of 250 ml dextrose in water 5%. The duration of the infusion is 1 hour and treatment is given every 12 hours daily for 7 days. In the case of oral placebo medication, this is given as oral tablets every 12 hours once for 7 days. Step-down from IV to oral medication, respectively, is permitted.

Drug: Placebo

Standard-of-care (SoC) and clarithromycin

ACTIVE COMPARATOR

In the case of IV medication, patients receive 500 mg of clarithromycin diluted with water for injection at a volume of 10ml and further diluted to a final volume of 250 ml dextrose in water 5%. The duration of the infusion is 1 hour and treatment is given every 12 hours daily for 7 days. In the case of oral medication, this is given as clarithromycin IR 500mg every 12 hours for 7 days. Step-down from IV to oral medication, respectively, is permitted.

Drug: clarithromycin

Interventions

Placebo DRUG

There is no other intervention in this clinical study and participation in another clinical study is an exclusion criterion.

Standard-of-care (SoC) and placebo

clarithromycin DRUG

There is no other intervention in this clinical study and participation in another clinical study is an exclusion criterion.

Standard-of-care (SoC) and clarithromycin

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
• Patients of either gender
• Written informed consent provided by the patient. For patients without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation.
• Negative (blood or urinary) pregnancy test for female patients of reproductive age
• For female patients of reproductive age, willingness to use highly effective contraception during and seven days after the administration of the IMP.
• Presence of Community-acquired pneumonia (CAP)
• Presence of sepsis as defined by the Sepsis-3 classification criteria (at least 2 points increase of the total SOFA-1 score from the baseline score of the specific patient). The SOFA score which will be used for the definition of sepsis has recently been renamed SOFA-1.
• Absolute lymphocyte count (ALC) less than 1000/mm³.

You may not qualify if:

• Age below 18 years
• Denial of written informed consent
• Pregnancy (confirmed by blood or urinary pregnancy test) or lactation for female patients
• Unwillingness to receive contraception during and seven days after the administration of the IMPstudy drug (for Female patients)
• Known HIV infection with known CD4 cell count \<200/mm³
• Solid organ or bone marrow transplantation
• Corticosteroid oral or intravenous intake greater than 0.4mg/kg of equivalent prednisone daily over the last 15 days or other immunosuppressive therapy. However, corticosteroids received as adjunctive treatment for the current septic/infectious episode are allowed
• Intake of a biological agent in the last month
• Known active neoplasms or other conditions unrelated to sepsis that compromise short-term survival less than 6 months
• Neutropenia \< 500/mm³
• Intake of any macrolide for the current episode of CAP under study
• QTc interval at rest in the ECG ≥500 msec or history of known long QT syndrome
• Medical history of allergy to macrolides
• Concomitant use of medicinal products contraindicated with clarithromycin, including CYP3A substrates associated with QT prolongation (e.g., astemizole, cisapride, domperidone, pimozide, terfenadine, ivabradine), ergot alkaloids (e.g., ergotamine, dihydroergotamine), oral midazolam, HMG-CoA reductase inhibitors primarily metabolised by CYP3A4 (e.g., lovastatin, simvastatin), colchicine, ticagrelor, and ranolazine. This criterion applies to all medicinal products within these classes, not only the specific examples listed, in accordance with the SmPC for clarithromycin. Patients may be enrolled provided that such medications are discontinued prior to or at the time of trial participation. Given their short half-life, no wash-out period is required
• Medical history of torsades de pointes arrhythmia

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (19)

General University Hospital of Patras, Department of Internal Medicine

Pátrai, Achaea, 265 04, Greece

RECRUITING

Evaggelismos Hospital, 1st Department of Internal Medicine

Athens, Attica, 106 76, Greece

RECRUITING

General Hospital of Athens Korgialenio Benakio H.R.C, Intensive Care Unit

Athens, Attica, 115 26, Greece

RECRUITING

General Hospital of Athens Korgialenio Benakio H.R.C., 1st Department of Internal Medicine

Athens, Attica, 115 26, Greece

RECRUITING

General Hospital of Athens G.Gennimatas, 1st Department of Internal Medicine

Athens, Attica, 115 27, Greece

RECRUITING

Thoracic General Hospital of Athens I Sotiria, 3rd University Department of Internal Medicine

Athens, Attica, 115 27, Greece

RECRUITING

Thoracic General Hospital of Athens I Sotiria, 6th Department of Pulmonary Medicine

Athens, Attica, 115 27, Greece

RECRUITING

General Hospital of Athens Alexandra, Ηigh Dependency Unit of Department of Clinical Therapeutics

Athens, Attica, 115 28, Greece

RECRUITING

University General Hospital Attikon-General Hospital of West Attica H Agia Varvara, 2nd Department of Propaedeutic Medicine

Athens, Attica, 124 61, Greece

RECRUITING

University General Hospital Attikon-General Hospital of West Attica H Agia Varvara, 4th Department of Internal Medicine

Athens, Attica, 124 61, Greece

RECRUITING

General Oncological Hospital of Kifisia Agioi Anargyroi, Intensive Care Unit

Athens, Attica, 145 64, Greece

RECRUITING

University General Hospital of Ioannina, 1st Department of Internal Medicine

Ioannina, Ioannina, 455 00, Greece

NOT YET RECRUITING

University General Hospital of Thessaloniki Ahepa, Intensive Care Unit

Thessaloniki, Thessaloniki, 546 36, Greece

NOT YET RECRUITING

Ippokratio General Hospital of Thessaloniki, 2nd Propaedeutic Department of Internal Medicine

Thessaloniki, Thessaloniki, 546 42, Greece

RECRUITING

General Hospital of Thessaloniki Papageorgiou, Department of Internal Medicine

Thessaloniki, Thessaloniki, 564 29, Greece

RECRUITING

Geniko Nosokomeio Thessalonikis George Papanikolaou, Intensive Care Unit

Thessaloniki, Thessaloniki, 570 10, Greece

RECRUITING

University General Hospital of Alexandroupolis, 2nd Department of Internal Medicine

Alexandroupoli, Thrace, 681 00, Greece

NOT YET RECRUITING

General Hospital of Eleusina Thriasio, 1st Department of Internal Medicine

Elefsina, West Attica, 190 18, Greece

NOT YET RECRUITING

General Hospital of Eleusina Thriasio, 2nd Department of Internal Medicine

Elefsina, West Attica, 190 18, Greece

NOT YET RECRUITING

MeSH Terms

Conditions

Sepsis; Community-Acquired Pneumonia

Interventions

Clarithromycin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Community-Acquired Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Evangelos J Giamarellos-Bourboulis, Professor

  Hellenic Institute for the Study of Sepsis

  STUDY CHAIR

Central Study Contacts

Evangelos J Giamarellos-Bourboulis, Professor

CONTACT

2105831994; egiamarel@med.uoa.gr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 22, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 2, 2026

Record last verified: 2026-09

Locations

GR (19)