Clarithromycin Treatment to Prevent Sepsis Progression in CAP (REACT)
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.
- EligibilityCriteria: 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 - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult