Sepsis Clinical Trial
— ACCESSOfficial title:
A Randomized Clinical Trial of Oral Clarithromycin in Community-acquired Pneumonia to Attenuate Inflammatory Responses and Improve Outcomes: the ACCESS Clinical Trial
Verified date | December 2023 |
Source | Hellenic Institute for the Study of Sepsis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Traditional management of community-acquired pneumonia (CAP) relies on the prompt administration of antimicrobials that target the most common causative pathogens. Retrospective analysis of observational clinical studies in CAP showed that the addition of macrolides to standard antibiotic therapy conferred a significant survival benefit. The proposed benefit of macrolides is coming from their anti-inflammatory mode of action. An RCT that proves the attenuation of the high inflammatory burden of the host with CAP after addition of clarithromycin in the treatment regimen is missing. This RCT is aiming to prove that addition of oral clarithromycin to a β-lactam rapidly attenuates the high inflammatory burden of the host in CAP.
Status | Completed |
Enrollment | 278 |
Est. completion date | April 11, 2023 |
Est. primary completion date | April 11, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Adult patients (=18 years) - Male of female gender - In case of non-menopausal women, unwillingness to become pregnant during the study period. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study. - Written informed consent provided by the patients or by a first-degree relative in case of patients unable to consent - Presence of at least two signs of SIRS (see below for definition) - SOFA score =2 (see Appendix I) - PCT =0.25 ng/ml - Presence of at least two of the following signs: i) cough; ii) purulent sputum expectoration; iii) dyspnea; and/or iv) pleuritic chest pain - Presence of CAP (see below for definition) SIRS is defined by the presence of at least two of the following criteria: - Core temperature >38 Celsius degrees or <36 Celsius degrees - Heart rate >90 beats/minute - Breath rate >20 breaths/minute or pco2<32 mmHg - Total white blood cell count >12,000/mm3 or <4,000/mm3 or >15% bands CAP is defined as the presence of auscultatory findings compatible with CAP and new consolidation in chest X-ray in a patient without any history of contact with the hospital environment or with health-care facilities the last 90 days. Exclusion Criteria: - Age below 18 years - Denial of written informed consent - Presence of infection by SARS-CoV-2 (COVID-19) - Intake of any macrolide for the current episode of CAP under study - Oral or intravenous intake of corticosteroids defined as any more than 0.4mg/kg daily intake of equivalent prednisone for the last 15 days - Neutropenia defined as an absolute neutrophil count below 1,000/mm3 - Known infection by the human immunodeficiency virus - Any chronic anti-cytokine treatment (e.g. antibodies against TNF for rheumatoid arthritis) - Hospitalization for more than 2 days the last 90 days - QTc interval at rest ECG =500 msec or history of known congenital long QT syndrome - Concomitant administration with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4, (lovastatin or simvastatin), and presence of any contraindications for the study drug - Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study. |
Country | Name | City | State |
---|---|---|---|
Greece | 1st Department of Internal Medicine, Amalia Fleming General Hospital | Athens | |
Greece | 1st Department of Internal Medicine, Gennimatas General Hospital | Athens | |
Greece | 1st Department of Internal Medicine, Konstantopouleio-Patission General Hospital | Athens | |
Greece | 1st Department of Internal Medicine, THRIASIO Eleusis General Hospital | Athens | |
Greece | 1st Department of Internal Medicine,Korgialeneio-Benakeio General Hospital | Athens | |
Greece | 2nd Department of Internal Medicine, Attikon University Hospital | Athens | |
Greece | 2nd Department of Internal Medicine, Thriasio General Hospital | Athens | |
Greece | 3rd Department of Internal Medicine, KORGIALENEION-BENAKEION Athens General Hospital | Athens | |
Greece | 3rd Department of Internal Medicine, Sotiria General Hospital | Athens | |
Greece | 4th Department of Internal Medicine, Attikon University Hospital | Athens | |
Greece | 5th Department of Internal Medicine, Evangelismos General Hospital | Athens | |
Greece | Department of Chest Medicine, EVANGELISMOS Athens General Hospital | Athens | |
Greece | Department of Pulmonary Medicine, General Hospital of Kerkyra | Corfu | |
Greece | 1st Department of Internal Medicine, Ioannina University General Hospital | Ioannina | |
Greece | Department of Internal Medicine, Larissa University General Hospital | Larissa | |
Greece | Department of Internal Medicine, Patras University General Hospital | Patra | |
Greece | 2nd Department of Internal Medicine, Tzaneion General Hospital | Piraeus | |
Greece | Department of Emergency Medicine, Tzanneion General Hospital | Piraeus |
Lead Sponsor | Collaborator |
---|---|
Hellenic Institute for the Study of Sepsis |
Greece,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change of baseline respiratory symptoms score | At least 50 percent (%) decrease of the sum of scoring (0-12) for the symptoms of cough (0-3), dyspnea (0-3), purulent sputum expectoration (0-3) and pleuritic chest pain (0-3) between baseline and Study Day 4 | 4 days | |
Primary | Change of baseline total sequential organ failure assessment (SOFA) score and/or change of baseline serum PCT | At least 30 percent (%) decrease between baseline sequential organ failure assessment (SOFA) score and measured sequential organ failure assessment (SOFA) score at Study Day 4 and/or at least 80 percent (%) decrease of serum PCT from baseline PCT at Study Day 4 and/or serum PCT below 0.25 ng/ml at Study Day 4 | 4 days | |
Secondary | Change of baseline respiratory symptoms score in the subgroup of patients infected or colonized by clarithromycin-susceptible S.pneumoniae | Comparison of the number of patients reaching at least 50 percent (%) decrease of the sum of scoring (0-12) for the symptoms of cough (0-3), dyspnea (0-3), purulent sputum expectoration (0-3) and pleuritic chest pain (0-3) between baseline and Study Day 4, among clarithromycin and placebo-treated patients, infected or colonized by clarithromycin-susceptible S.pneumoniae | 4 days | |
Secondary | Change of baseline respiratory symptoms score in the subgroup of patients infected or colonized by clarithromycin-resistant S.pneumoniae | Comparison of the number of patients reaching at least 50 percent (%) decrease of the sum of scoring (0-12) for the symptoms of cough (0-3), dyspnea (0-3), purulent sputum expectoration (0-3) and pleuritic chest pain (0-3) between baseline and Study Day 4, among clarithromycin and placebo-treated patients, infected or colonized by clarithromycin-susceptible S.pneumoniae | 4 days | |
Secondary | Change of baseline total sequential organ failure assessment (SOFA) score and/or change of baseline serum PCT in the subgroup of patients infected or colonized by clarithromycin-susceptible S.pneumoniae | Comparison of the number of patients reaching at least 30 percent (%) decrease between baseline sequential organ failure assessment (SOFA) score and measured sequential organ failure assessment (SOFA) score at Study Day 4 and/or at least 80 percent (%) decrease of serum PCT from baseline at Study Day 4 and/or serum PCT below 0.25 ng/ml at Study Day 4, among clarithromycin and placebo-treated patients infected or colonized by clarithromycin-susceptible S.pneumoniae | 4 days | |
Secondary | Change of baseline total sequential organ failure assessment (SOFA) score and/or change of baseline serum PCT in the subgroup of patients infected or colonized by clarithromycin-resistant S.pneumoniae | Comparison of the number of patients reaching at least 30 percent (%) decrease between baseline sequential organ failure assessment (SOFA) score and measured sequential organ failure assessment (SOFA) score at Study Day 4 and/or at least 80 percent (%) decrease of serum PCT from baseline at Study Day 4 and/or serum PCT below 0.25 ng/ml at Study Day 4, among clarithromycin and placebo-treated patients infected or colonized by clarithromycin-resistant S.pneumoniae | 4 days | |
Secondary | Mortality rate at 28 days | Differences in 28-day all-cause mortality rate between clarithromycin and placebo-treated arms | 28 days | |
Secondary | Mortality rate at 90 days | Differences in 90-day all-cause mortality rate between clarithromycin and placebo-treated arms | 90 days | |
Secondary | Clinical success at the end of treatment Visit (day 8) | Difference in clinical success rate at day 8, as defined by at least 50 percent (%) decrease of the baseline sum of scoring (0-12) for the symptoms of cough (0-3), dyspnea (0-3), purulent sputum expectoration (0-3) and pleuritic chest pain (0-3) | 8 days | |
Secondary | Hospital discharge until day 90 | Comparison of length of hospital stay (days) until day 90 between clarithromycin and placebo-treated arms | 90 days | |
Secondary | Hospital readmission until day 90 | Comparison of hospital readmission rate until day 90 between clarithromycin and placebo-treated arms | 90 days | |
Secondary | Change of baseline total sequential organ failure assessment (SOFA) score at the end of treatment Visit (day 8) | Comparison of number of patients reaching more than 50 percent (%) decrease between baseline sequential organ failure assessment (SOFA) score and measured sequential organ failure assessment (SOFA) score at Study Day 8 between clarithromycin and placebo-treated arms | 8 days | |
Secondary | Development of new organ dysfunctions until day 90 | Comparison of the rate of development of new organ dysfunctions between clarithromycin and placebo-treated arms | 90 days | |
Secondary | Change of function of monocytes, Th1, Th2 and T17 cells at Study Visit 4 | Comparison of cytokine production by stimulation of monocytes, Th1,Th2 and T17 cells between clarithromycin and placebo-treated arms | 4 days | |
Secondary | Change of gene expression of anti-inflammatory genes at Study Visit 4 | Comparison of the expressions of four genes (FGL-2, IL7R, HLA-DPA1, CPVL), that are down-regulated upon development of severe infections, between clarithromycin and placebo-treated arms | 4 days | |
Secondary | Anti-inflammatory PCT change at study Visit 6 | Comparison of number of patients reaching at least 80 percent (%) decrease of serum PCT from baseline on day 6 or any value of PCT below 0.25 ng/ml on day 6 between clarithromycin and placebo-treated arms | 6 days | |
Secondary | Anti-inflammatory PCT change at the end of treatment Visit (day 8) | Comparison of number of patients reaching at least 80 percent (%) decrease of serum PCT from baseline on day 8 or any value of PCT below 0.25 ng/ml on day 8 between clarithromycin and placebo-treated arms | 8 days | |
Secondary | Change of the IL-10/TNFa ratio at study Visit 6 | Comparison of the change of the IL-10/TNFa ratio between baseline and day 6 among clarithromycin and placebo-treated arms | 6 days | |
Secondary | Change of the IL-10/TNFa ratio at the end of treatment Visit (day 8) | Comparison of the of the change of the IL-10/TNFa ratio between baseline and day 8 among clarithromycin and placebo-treated arms | 8 days | |
Secondary | New sepsis episode until day 90 | Comparison of the rate of development of new sepsis episode between clarithromycin and placebo-treated arms | 90 days | |
Secondary | Change of expression of the MVK gene at study Visit 4 | Comparison of the expression of the MVK gene, that affects the cholesterol homeostasis pathway, between clarithromycin and placebo-treated arms | 4 days | |
Secondary | Change of expression of the SC5D gene at study Visit 4 | Comparison of the expression of the SC5D gene, that affects the cholesterol homeostasis pathway, between clarithromycin and placebo-treated arms | 4 days | |
Secondary | Change of expression of the MVD gene at study Visit 4 | Comparison of the expression of the MVD gene, that affects the cholesterol homeostasis pathway, between clarithromycin and placebo-treated arms | 4 days | |
Secondary | Change of expression of the STARD4 gene at study Visit 4 | Comparison of the expression of the STARD4 gene, that affects the cholesterol homeostasis pathway, between clarithromycin and placebo-treated arms | 4 days | |
Secondary | Change of expression of the SQLE gene at study Visit 4 | Comparison of the expression of the SQLE gene, that affects the cholesterol homeostasis pathway, between clarithromycin and placebo-treated arms | 4 days |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT05095324 -
The Biomarker Prediction Model of Septic Risk in Infected Patients
|
||
Completed |
NCT02714595 -
Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens
|
Phase 3 | |
Completed |
NCT03644030 -
Phase Angle, Lean Body Mass Index and Tissue Edema and Immediate Outcome of Cardiac Surgery Patients
|
||
Completed |
NCT02867267 -
The Efficacy and Safety of Ta1 for Sepsis
|
Phase 3 | |
Completed |
NCT04804306 -
Sepsis Post Market Clinical Utility Simple Endpoint Study - HUMC
|
||
Recruiting |
NCT05578196 -
Fecal Microbial Transplantation in Critically Ill Patients With Severe Infections.
|
N/A | |
Terminated |
NCT04117568 -
The Role of Emergency Neutrophils and Glycans in Postoperative and Septic Patients
|
||
Completed |
NCT03550794 -
Thiamine as a Renal Protective Agent in Septic Shock
|
Phase 2 | |
Completed |
NCT04332861 -
Evaluation of Infection in Obstructing Urolithiasis
|
||
Completed |
NCT04227652 -
Control of Fever in Septic Patients
|
N/A | |
Enrolling by invitation |
NCT05052203 -
Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
|
||
Terminated |
NCT03335124 -
The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock
|
Phase 4 | |
Recruiting |
NCT04005001 -
Machine Learning Sepsis Alert Notification Using Clinical Data
|
Phase 2 | |
Completed |
NCT03258684 -
Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis and Septic Shock
|
N/A | |
Recruiting |
NCT05217836 -
Iron Metabolism Disorders in Patients With Sepsis or Septic Shock.
|
||
Completed |
NCT05018546 -
Safety and Efficacy of Different Irrigation System in Retrograde Intrarenal Surgery
|
N/A | |
Completed |
NCT03295825 -
Heparin Binding Protein in Early Sepsis Diagnosis
|
N/A | |
Not yet recruiting |
NCT06045130 -
PUFAs in Preterm Infants
|
||
Not yet recruiting |
NCT05361135 -
18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in S. Aureus Bacteraemia
|
N/A | |
Not yet recruiting |
NCT05443854 -
Impact of Aminoglycosides-based Antibiotics Combination and Protective Isolation on Outcomes in Critically-ill Neutropenic Patients With Sepsis: (Combination-Lock01)
|
Phase 3 |