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The aim of this clinical trial is to clarify the clinical efficacy of clarithromycin as immunotherapy for the management of septic syndrome by ventilator-associated pneumonia.
The rationale of the trial is based on the favorable results of experimental studies of sepsis by multidrug-resistant Pseudomonas aeruginosa and by susceptible Escherichia coli in rabbits where clarithromycin was administered intravenously. Data from these latter studies suggest that administration of clarithromycin extended survival and attenuated systemic inflammatory response. Their major endpoint was successful immunotherapy achieved when clarithromycin was administered on presentation of symptoms of sepsis-induced pulmonary edema; on the contrary, former clinical trials for immunotherapies of sepsis were based on animal studies where the under evolution immunomodulator was administered before bacterial challenge. The efficacy of administration of clarithromycin upon presentation of septic syndrome in animal studies, renders its application promising in the clinical field.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous Clarithromycin | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Estimation of crude mortality by any reason of each study group | ||
| Estimation of attributable mortality by VAP of each study group | ||
| 7-day mortality rate of each group | ||
| 28-mortality rate of each group | ||
| Rate of progression to multiple organ failure and septic shock (and number of failing organs) of each study group | ||
| Time to progression to multiple organ failure and septic shock of each study group | ||
| Days of resolution of VAP | ||
| Days in ICU after diagnosis of VAP |
| Measure | Description | Time Frame |
|---|---|---|
| Influence of administration of clarithromycin on systemic inflammatory response |
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Inclusion Criteria:
d) diagnosis of Ventilator Associated Pneumonia; and e) signs of sepsis
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Evangelos J Giamarellos-Bourboulis, MD, PhD | University of Athens, Medical School, Greece | Study Chair |
| Helen Giamarellou, MD, PhD | University of Athens, Medical School, Greece | Principal Investigator |
| Apostolos Armaganidis, MD, PhD | University of Athens, Medical School, Greece | Principal Investigator |
| Charis Roussos, MD, PhD | University of Athens, Medical School, Greece | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1st Department of Critical Care, Evangelismos General Hospital | Athens | 106 72 | Greece | |||
| 2nd Department of Critical Care, ATTIKON University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14693524 | Background | Giamarellos-Bourboulis EJ, Adamis T, Laoutaris G, Sabracos L, Koussoulas V, Mouktaroudi M, Perrea D, Karayannacos PE, Giamarellou H. Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2004 Jan;48(1):93-9. doi: 10.1128/AAC.48.1.93-99.2004. | |
| 15664488 |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D053717 | Pneumonia, Ventilator-Associated |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| Athens |
| 124 64 |
| Greece |
| 4th Department of Internal Medicine, ATTIKON University Hospital | Athens | 124 64 | Greece |
| Giamarellos-Bourboulis EJ, Baziaka F, Antonopoulou A, Koutoukas P, Kousoulas V, Sabracos L, Panagou C, Perrea D, Giamarellou H. Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli. Int J Antimicrob Agents. 2005 Feb;25(2):168-72. doi: 10.1016/j.ijantimicag.2004.08.018. |
| 15764190 | Background | Giamarellos-Bourboulis E, Adamis T, Sabracos L, Raftogiannis M, Baziaka F, Tsaganos T, Koutoukas P, Plachouras D, Karayannacos P, Giamarellou H. Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli. Scand J Infect Dis. 2005;37(1):48-54. doi: 10.1080/00365540510026832. |
| 34871241 | Derived | Vittoros V, Kyriazopoulou E, Lada M, Tsangaris I, Koutelidakis IM, Giamarellos-Bourboulis EJ. Soluble fms-like tyrosine kinase 1, placental growth factor and procalcitonin as biomarkers of gram-negative sepsis: Analysis through a derivation and a validation cohort. Medicine (Baltimore). 2021 Nov 5;100(44):e27662. doi: 10.1097/MD.0000000000027662. |
| 31783881 | Derived | Karakike E, Kyriazopoulou E, Tsangaris I, Routsi C, Vincent JL, Giamarellos-Bourboulis EJ. The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort. Crit Care. 2019 Nov 29;23(1):387. doi: 10.1186/s13054-019-2665-5. |
| 29741298 | Derived | Strouvalis I, Routsi C, Adamopoulou M, Raftogiannis M, Renieris G, Orfanos SE, Kotanidou A, Sabracos L, Giamarellos-Bourboulis EJ. Early increase of VEGF-A is associated with resolution of ventilator-associated pneumonia: Clinical and experimental evidence. Respirology. 2018 Oct;23(10):942-949. doi: 10.1111/resp.13320. Epub 2018 May 9. |
| 27044546 | Derived | Tsaganos T, Raftogiannis M, Pratikaki M, Christodoulou S, Kotanidou A, Papadomichelakis E, Armaganidis A, Routsi C, Giamarellos-Bourboulis EJ. Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis. Antimicrob Agents Chemother. 2016 May 23;60(6):3640-6. doi: 10.1128/AAC.02974-15. Print 2016 Jun. |
| 18707849 | Derived | Giamarellos-Bourboulis EJ. Immunomodulatory therapies for sepsis: unexpected effects with macrolides. Int J Antimicrob Agents. 2008 Nov;32 Suppl 1:S39-43. doi: 10.1016/j.ijantimicag.2008.06.004. Epub 2008 Aug 15. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D000077299 | Healthcare-Associated Pneumonia |
| D003428 | Cross Infection |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |