Clarithromycin to Prevent Secondary Infections in Patients with Sepsis Following Lower Respiratory Tract Infections: the Classify Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Elliniko Institouto Meletis Tis Sipsis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-06-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Therapy, Efficacy

The CLASSIFY trial is designed to determine whether adjunctive clarithromycin, administered IV or orally, can reduce the incidence of secondary infection episodes including sepsis within 28 days among patients with CAP-related sepsis and evidence of SII.

Conditions and MedDRA coding

Community- acquired pneumonia related sepsis with evidence of Sepsis Induced Immunoparalysis SII

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age equal to or above 18 years
2. Patients of either gender
3. 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.
4. Negative (blood or urinary) pregnancy test for female patients of reproductive age
5. For female patients of reproductive age, willingness to use contraception during and seven days after the administration of the study drug.
6. Presence of Community-acquired pneumonia (CAP)
7. 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.
8. Absolute lymphocyte count (ALC) less than 1000/mm³.

Exclusion criteria 20

1. Age below 18 years
2. Neutropenia defined as an absolute neutrophil count less than 500/mm³
3. Intake of macrolide for the current episode of CAP under study
4. Corrected QT interval at rest in the ECG ≥500 msec or history of known long QT syndrome
5. Medical history of allergy to macrolides
6. 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
7. Medical history of torsades de pointes arrhythmia
8. Denial of written informed consent
9. Pregnancy (confirmed by blood or urinary pregnancy test) or lactation for female patients
10. Unwillingness to receive contraception during and seven days after the administration of the study drug (for Female patients)
11. Known HIV infection with known CD4 cell count ≤ 200/mm³
12. Solid organ, or bone marrow transplantation
13. Corticosteroid oral or intravenous intake greater than 0.4 mg/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
14. Intake of a biological agent in the last month
15. Known active neoplasms or other conditions unrelated to sepsis that compromise short-term survival to less than 6 months.
16. Severe hypokalemia or severe hypomagnesemia; a patient may be enrolled one any of these electrolyte disturbances are restored.
17. Any contraindications for macrolide uptake
18. Participation in any other interventional trial within the last 30 days
19. Previous participation in the CLASSIFY study
20. Patients with severe hepatic failure or severe renal dysfunction may be excluded at the discretion of the attending physician

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. The impact of intravenous or oral clarithromycin as adjunctive treatment to SoC antibiotic therapy compared to placebo on the incidence of new infection. This is a composite endpoint incorporating any of the following
2. Worsening of the episode of CAP for which the patient is enrolled in the study. “Worsening” is defined as need to change SoC during the first 7 days of the study. Change of the SoC to moxifloxacin because of detection of atypical pathogens is not considered worsening of the episode of CAP.
3. Any recurrence of the symptoms of the episode of CAP under study despite improvement after the first 7 days. “Recurrence of symptoms” is defined at the discretion of the attending physician and necessitates the start of new treatment or change of administered treatment after 7 days.
4. Any new infection of any other site than the lung during the first 28 days from inclusion in the study
5. Any episode of secondary sepsis between day 8 (stop of the study drug) and day 28 of follow-up. This outcome is defined as either onset of any new infection or recrudescence of the episode of CAP under study accompanied by at least 2-point increase of the total SOFA-1 compared to the SOFA-1 score before the onset of the new infection or the recurrence of CAP under study.

Secondary endpoints 12

1. All-cause 28-day mortality
2. All-cause 90-day mortality
3. Sepsis response: this is defined as at least 25% decrease of the day 1 (pre-treatment) SOFA-1 score by day 7
4. Type of new sepsis episode (predominant pathogen and site of infection)
5. Each of the elements of the composite primary endpoint separately
6. Time to antimicrobial escalation (days).
7. Need for hospital re-admission by day 90
8. Analysis of all secondary endpoints for the subgroup of patients defined by each appropriate treatment pathway.
9. Comparison of outcomes between patients who receive IV clarithromycin.
10. Patient status self-report documented by the EQ-5D questionnaire or a bespoke visual-analog scale.
11. Incremental cost-effectiveness ratios (ICERs) will be calculated and cross-referenced to patients’ health status for both treatment assignments.
12. Biomarkers of sepsis-induced immunosuppression through serial measurement of IFNγ, absolute number of HLA-DR receptors, TNFα by ex-vivo stimulation analysis, serum lipids, ferritin, sTREM-1, sTNFR-1, IL-6, IL-8, protein C and PAI-1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Elliniko Institouto Meletis Tis Sipsis

Sponsor organisation

Elliniko Institouto Meletis Tis Sipsis

Address

Laodikias 17

City

Athens

Postcode

115 28

Country

Greece

Scientific contact point

Organisation

Elliniko Institouto Meletis Tis Sipsis

Contact name

President of the Board

Public contact point

Organisation

Elliniko Institouto Meletis Tis Sipsis

Contact name

President of the Board

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications