CLARITHROMYCIN for Community-acquired pneumonia | Sepsis

Inclusion criteria

• {"criterion_text":"- Age equal to or above 18 years"}
• {"criterion_text":"- Male or female gender"}
• {"criterion_text":"- In case of women of reproductive age, willingness to use dual contraceptive method during the study period"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain"}
• {"criterion_text":"- Community-acquired pneumonia (CAP)"}
• {"criterion_text":"- PCT ≥0.25 ng/ml"}
• {"criterion_text":"- suPAR ≥6 ng/ml"}

Exclusion criteria

• {"criterion_text":"- Age below 18 years"}
• {"criterion_text":"- Concomitant oral intake of astemizole, cizapride, doperidone, pimozide, terfenadine, midazolam, ranolazine, ergot alkaloids (e.g. ergotamine and dihydroergotamine), lomitapide and colchicine; patients may be enrolled in the trial if they stop these drugs during trial participation."}
• {"criterion_text":"- Denial of written informed consent"}
• {"criterion_text":"- Any stage IV malignancy"}
• {"criterion_text":"- Any do not resuscitate decision"}
• {"criterion_text":"- Patients necessitating non-invasive ventilation or mechanical ventilation"}
• {"criterion_text":"- Hospitalization in Intensive Care Unit"}
• {"criterion_text":"- Infection by SARS-CoV-2"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Intake of any macrolide for the current episode of CAP under study"}
• {"criterion_text":"- Known infection by the human immunodeficiency virus"}
• {"criterion_text":"- Any chronic anti-cytokine treatment for more than two months"}
• {"criterion_text":"- QTc interval at rest in the ECG ≥500 msec or history of know long QT syndrome"}
• {"criterion_text":"- Medical history of allergy to macrolides"}
• {"criterion_text":"- Medical history of torsades de pointes arrhythmia"}
• {"criterion_text":"- Concomitant intake of lovostatin or simvastatin; patients may be enrolled in the trial if they stop these drugs during trial participation."}
• {"criterion_text":"- Concomitant presence of end-stage liver failure and end-stage renal failure."}
• {"criterion_text":"- Severe hypokalemia or severe hypomagnesemia; a patient may be enrolled one any of these electrolyte disturbances are restored."}
• {"criterion_text":"- Any contradictions for macrolide uptake"}
• {"criterion_text":"- Participation in any other interventional trial"}
• {"criterion_text":"- Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study"}

Primary endpoints

• {"endpoint_text":"- This is defined on day 4 and it is a composite endpoint of three conditions. Only patients meeting ALL three conditions will be considered as succeeding the primary endpoint.","definition_or_measurement_approach":"Defined on day 4 as a composite of three specific conditions; only patients meeting all three conditions succeed the primary endpoint."}
• {"endpoint_text":"- Condition A RSS i.e. the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain on visit 4 is decreased by at least 50% from the baseline score of day 1 without the development of any new symptom","definition_or_measurement_approach":"Respiratory Symptom Score (RSS): sum of scores for cough, dyspnea, purulent sputum expectoration and pleuritic chest pain on visit 4 decreased by ≥50% from baseline (day 1) with no new symptom."}
• {"endpoint_text":"- Condition B SOFA score on visit 4 is decreased by at least 30% from the baseline SOFA score of day 1","definition_or_measurement_approach":"Change in SOFA score: SOFA at visit 4 decreased by ≥30% from baseline SOFA on day 1."}
• {"endpoint_text":"- Condition C Combination of: (Plasma PCT on visit 4 has decreased by at least 80% from baseline PCT on screening or it is below 0.25 ng/ml) AND ([plasma IL-10 on visit 4 has decreased by at least 25% from IL-10 of visit 1 or it is below the lower limit of detection] or [the IL-8 to IL-10 ratio of day 4 has decreased less than 15% from the IL- 8 to IL-10 ratio of visit 1]).","definition_or_measurement_approach":"Laboratory biomarker criteria at visit 4: PCT decrease ≥80% from baseline or <0.25 ng/ml AND (IL-10 decrease ≥25% from visit 1 or below LOD OR IL-8/IL-10 ratio on day 4 decreased less than 15% from visit 1)."}
• {"endpoint_text":"- It is explicitly stated that patients dying prior to day 4 are considered failing the primary endpoint.","definition_or_measurement_approach":"Patients who die prior to day 4 are counted as failing the primary endpoint."}

Secondary endpoints

• {"endpoint_text":"- Development of new organ dysfunctions until day 28","definition_or_measurement_approach":"Occurrence of new organ dysfunctions up to day 28."}
• {"endpoint_text":"- Progression into sepsis","definition_or_measurement_approach":"Development/progression to sepsis (as defined in study procedures)."}
• {"endpoint_text":"- Clinical success at the TOC visit; this is also analyzed separately for patients infected or colonized by clarithromycin-susceptible and clarithromycin-resistant S.pneumoniae","definition_or_measurement_approach":"Clinical success at test-of-cure (TOC) visit; subgroup analysis by clarithromycin susceptibility of S. pneumoniae."}
• {"endpoint_text":"- Need for up-escalation of the SoC administered antibiotics. This is considered as the change of the baseline administered SoC antibiotics into more broad-spectrum antibiotics.","definition_or_measurement_approach":"Need for escalation defined as change from baseline standard-of-care antibiotics to broader-spectrum antibiotics."}
• {"endpoint_text":"- Alive hospital discharge until day 28","definition_or_measurement_approach":"Discharge alive from hospital by day 28."}
• {"endpoint_text":"- Achievement of more than 50% decrease of baseline SOFA score at EOT visit","definition_or_measurement_approach":"SOFA score at end of treatment (EOT) decreased by >50% compared with baseline (day 1)."}
• {"endpoint_text":"- Score of improvement of CAP-associated immune dysregulation (see sections of Laboratory procedures) at the EOT visit","definition_or_measurement_approach":"Score assessing improvement of CAP-associated immune dysregulation measured at EOT per laboratory procedures."}
• {"endpoint_text":"- Change of cytokine production by PBMCs: IL -6, IL-8, IL-10, TNFα on day 4 from visit 1.","definition_or_measurement_approach":"Change in cytokine production by PBMCs (IL-6, IL-8, IL-10, TNFα) on day 4 versus day 1."}
• {"endpoint_text":"- Association of 28-day mortality with the score of improvement of CAP-associated immune dysregulation","definition_or_measurement_approach":"Correlation between 28-day mortality and improvement score of CAP-associated immune dysregulation."}
• {"endpoint_text":"- Association of 90-day mortality with score of improvement of CAP- associated immune dysregulation","definition_or_measurement_approach":"Correlation between 90-day mortality and improvement score of CAP-associated immune dysregulation."}
• {"endpoint_text":"- Cost of hospital stay","definition_or_measurement_approach":"Economic endpoint: hospital stay cost."}
• {"endpoint_text":"- Comparison of 28-day mortality between screening failure patients due to SuPAR <6 ng/ml and/or PCT <0.25 ng/ml, and patients randomized to the placebo group","definition_or_measurement_approach":"Comparison of 28-day mortality between screening-fail patients (SuPAR <6 ng/ml and/or PCT <0.25 ng/ml) and randomized placebo group."}

Greece

Earliest CTIS Part Ii Submission Date

16-10-2023

Latest Decision Or Authorization Date

09-10-2025

Processing Time Days

724

Number Of Sites

29

Number Of Participants

330

Primary sponsor

Full Name

Hellenic Institute For The Study Of Sepsis

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Greece

Third parties

• {"country":"Greece","full_name":"Sustchem Techniki Symvouleftiki S.A.","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}