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RECRUITINGPhase 3INTERVENTIONAL

Clarithromycin Treatment to Prevent Sepsis Progression in CAP (REACT)

Biomarker-Guided Early Elarithromycin Treatment to Prevent Sepsis Progression in Community-Acquired Pneumonia: The React Randomized Clinical Trial

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The primary objective of the REACT randomized clinical trial (RCT) is to optimize the clinical benefit from adjunctive clarithromycin treatment shown in the ACCESS trial and to provide evidence for the clinical benefit of early start of adjunctive oral clarithromycin guided by suPAR to prevent the progression into sepsis in patients with community-acquired pneumonia (CAP) at risk. This can be achieved by endpoints incorporating clinical benefit with the effect of treatment on the improvement of the immune dysregulation of CAP. The secondary objectives of REACT are to investigate the impact of early adjunctive treatment with clarithromycin on the resolution of CAP at the test-of-cure (TOC) visit.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 willing to sign a consent form provided by the patient. For subjects without decision-making capacity, willing to sign a consent form must be obtained from a legally designated representative following the national legislation - Community-acquired pneumonia (CAP) - Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain - PCT ≥0.25 ng/ml - suPAR ≥6 ng/ml Who Should NOT Join This Trial: - Age below 18 years - Denial of written willing to sign a consent form - Any stage IV malignancy - Any do not resuscitate decision - Patients necessitating non-invasive ventilation or mechanical ventilation - Hospitalization in Intensive Care Unit - Infection by SARS-CoV-2 - 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 - Intake of any macrolide for the current episode of CAP under study - Known infection by the human weakened immune system virus - Any chronic anti-cytokine treatment for more than two months - QTc interval at rest in the ECG ≥500 msec or history of know long QT syndrome - Medical history of allergy to macrolides - 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. - Medical history of torsades de pointes arrhythmia - Concomitant intake of lovostatin or simvastatin; patients may be enrolled in the trial if they stop these drugs during trial participation. - Concomitant presence of end-stage liver failure and end-stage renal failure. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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 * Community-acquired pneumonia (CAP) * Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain * PCT ≥0.25 ng/ml * suPAR ≥6 ng/ml Exclusion Criteria: * Age below 18 years * Denial of written informed consent * Any stage IV malignancy * Any do not resuscitate decision * Patients necessitating non-invasive ventilation or mechanical ventilation * Hospitalization in Intensive Care Unit * Infection by SARS-CoV-2 * 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 * Intake of any macrolide for the current episode of CAP under study * Known infection by the human immunodeficiency virus * Any chronic anti-cytokine treatment for more than two months * QTc interval at rest in the ECG ≥500 msec or history of know long QT syndrome * Medical history of allergy to macrolides * 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. * Medical history of torsades de pointes arrhythmia * Concomitant intake of lovostatin or simvastatin; patients may be enrolled in the trial if they stop these drugs during trial participation. * Concomitant presence of end-stage liver failure and end-stage renal failure. * Severe hypokalemia or severe hypomagnesemia; a patient may be enrolled one any of these electrolyte disturbances are restored. * Any contradictions for macrolide uptake * Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study * Participation in any other interventional trial within the last 30 days

Treatments Being Tested

DRUG

Clarithromycin 500mg

Oral tablets of 500mg of clarithromycin

DRUG

Tablets

Oral tablets of similar appearance to active study drug

Locations (20)

5th Pulmonary Department, SOTIRIA Athens General Hospital of Chest Diseases
Athens, Athens, Greece
1st Department of Internal Medicine - General Hospital of Athens "Sismanogleio-Amalia Fleming"
Athens, Greece, Greece
1st Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki
Athens, Greece, Greece
1st Department of Internal Medicine, EVANGELISMOS Athens General Hospital
Athens, Greece, Greece
1st Department of Internal Medicine, G. GENNIMATAS Athens General Hospital
Athens, Greece, Greece
1st Department of Internal Medicine, General University Hospital of Ioannina
Athens, Greece, Greece
1st Department of Internal Medicine, KORGIALENEIO-BENAKEIO E.E.S. Athens General Hospital
Athens, Greece, Greece
1st Department of Internal Medicine, THRIASIO General Hospital of Elefsis
Athens, Greece, Greece
1st University Department of Pulmonary Medicine, SOTIRIA General Hospital of Chest Diseases of Athens
Athens, Greece, Greece
2nd Department of Internal Medicine, Attikon University Hospital
Athens, Greece, Greece
2nd Department of Internal Medicine, THRIASIO General Hospital of Elefsis
Athens, Greece, Greece
2nd Department of Internal Medicine, TZANEIO Piraeus General Hospital
Athens, Greece, Greece
2nd Department of Internal Medicine, University General Hospital of Alexandroupolis
Athens, Greece, Greece
3rd Department of Internal Medicine - General State Hospital of Nikaia "Saint Panteleimon" - West Attica General Hospital
Athens, Greece, Greece
3rd Department of Internal Medicine, General Hospital of Athens KORGIALENEIO- BENAKEIO E.E.S.
Athens, Greece, Greece
3rd University Department of Internal Medicine, SOTIRIA Athens General Hospital of Chest Diseases
Athens, Greece, Greece
4th Department of Internal Medicine, Attikon University Hospital
Athens, Greece, Greece
6th Pulmonary Medicine Department, SOTIRIA General Hospital of Chest Diseases of Athens
Athens, Greece, Greece
Department of Chest Medicine, EVANGELISMOS Athens General Hospital
Athens, Greece, Greece
Department of Internal Medicine, Larissa University General Hospital
Athens, Greece, Greece