Sepsis Clinical Trial
— PROVIDEOfficial title:
A Personalized Randomized Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis
Verified date | July 2020 |
Source | Hellenic Institute for the Study of Sepsis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The aim of the study is to conduct one RCT of personalized immunotherapy in sepsis targeting patients who lie either on the predominantly hyper-inflammatory arm or on the predominantly hypo-inflammatory arm of the spectrum of the host response. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be randomly allocated to placebo or immunotherapy treatment according to their needs.
Status | Completed |
Enrollment | 36 |
Est. completion date | December 31, 2019 |
Est. primary completion date | December 31, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Age equal to or above 18 years - Male or female gender - In case of women, unwillingness to remain pregnant during the study period - Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent - Community-acquired pneumonia or hospital-acquired pneumonia or ventilator-associated pneumonia or primary bacteremia or acute cholangitis - Sepsis defined by the Sepsis-3 definitions. - Patients with laboratory diagnosis of MALS or hypo-inflammation (immune-paralysis) based on two consecutive blood sampling with 24 hours apart. MALS is defined as the presence of ferritin >4,420 ng/ml and hypo-inflammation as HLA-DR expression on CD14-monocytes (co-expression) less than 30% Exclusion Criteria: - Age below 18 years - Denial for written informed consent - Acute pyelonephritis or intraabdominal infection other than AC, meningitis or skin infection. It is explicitly stated that in the case of a patient with both AC and any other type of intraabdominal infection, the patient cannot be enrolled. - Any stage IV malignancy - Any do not resuscitate decision - In the case of BSI, patients with blood cultures growing coagulase-negative staphylococci or skin commensals or catheter-related infections cannot be enrolled. - Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB - Infection by the human immunodeficiency virus (HIV) - Any primary immunodeficiency - Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg prednisone or greater the last 15 days - Any anti-cytokine biological treatment the last one month - Medical history of systemic lupus erythematosus - Medical history of multiple sclerosis or any other demyelinating disorder - 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 | Intensive Care Unit, Alexandroupolis University Hospital | Alexandroupolis | |
Greece | 1st Department of Pulmonary Medicine and Intensive Care Unit | Athens | |
Greece | 2nd Department of Critical Care Medicine | Athens | Haidari |
Greece | 4th Department of Internal Medicine | Athens | Haidari |
Greece | Intensive Care Unit, Center for Accident Rehabilitation (KAT) of Athens | Athens | Kifissia |
Greece | Intensive Care Unit, "Latsio", Thriasio Elefsis General Hospital | Elefsína | |
Greece | Intensive Care Unit, Ioannina University Hospital | Ioánnina | Ioannina |
Greece | Department of Internal Medicine, Larissa University Hospital | Larissa | |
Greece | Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General Hospital | Larissa | |
Greece | Department of Internal Medicine, Patras University Hospital | Patras | Rion |
Greece | Intensive Care Unit, "Tzanio" Piraeus General Hospital | Piraeus | |
Greece | Intensive Care Unit, "Aghios Dimitrios" Thessaloniki General Hospital | Salónica | |
Greece | Intensive Care Unit, "G.Gennimatas" Thessaloniki General Hospital | Salónica |
Lead Sponsor | Collaborator |
---|---|
Hellenic Institute for the Study of Sepsis |
Greece,
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Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of Adults Wit — View Citation
Kyriazopoulou E, Leventogiannis K, Norrby-Teglund A, Dimopoulos G, Pantazi A, Orfanos SE, Rovina N, Tsangaris I, Gkavogianni T, Botsa E, Chassiou E, Kotanidou A, Kontouli C, Chaloulis P, Velissaris D, Savva A, Cullberg JS, Akinosoglou K, Gogos C, Armagani — View Citation
Leentjens J, Kox M, Koch RM, Preijers F, Joosten LA, van der Hoeven JG, Netea MG, Pickkers P. Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study. Am J Respir Crit Care Med. 2012 Nov 1;186(9):838-45. d — View Citation
Opal SM, Fisher CJ Jr, Dhainaut JF, Vincent JL, Brase R, Lowry SF, Sadoff JC, Slotman GJ, Levy H, Balk RA, Shelly MP, Pribble JP, LaBrecque JF, Lookabaugh J, Donovan H, Dubin H, Baughman R, Norman J, DeMaria E, Matzel K, Abraham E, Seneff M. Confirmatory — View Citation
Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M, Oikonomou A, Poulakou G, Roilides E, Giamarellou H. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and exte — View Citation
Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, Cron RQ, Opal SM. Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III — View Citation
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International C — View Citation
Zilberberg MD, Shorr AF. Ventilator-associated pneumonia: the clinical pulmonary infection score as a surrogate for diagnostics and outcome. Clin Infect Dis. 2010 Aug 1;51 Suppl 1:S131-5. doi: 10.1086/653062. Review. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Mortality | Mortality will be compared between the groups of treatment | 28 days | |
Secondary | Mortality | Mortality will be compared between the groups of treatment | 90 days | |
Secondary | Time to decrease of SOFA score by more than 50% | The time to decrease of SOFA score by more than 50% will be compared between the groups of treatment | 28 days | |
Secondary | Time to infection resolution | The time to infection resolution will be compared between the groups of treatment | 28 days | |
Secondary | Duration of hospitalisation | The duration of hospitalisation will be compared between the groups of treatment | 28 days | |
Secondary | Number of secondary infections | The number of secondary infections will be compared between the groups of treatment | 28 days | |
Secondary | Cytokine stimulation | Cytokine stimulation from peripheral blood mononuclear cells will be compared between the groups of treatment | 4 days | |
Secondary | Cytokine stimulation | Cytokine stimulation from peripheral blood mononuclear cells will be compared between the groups of treatment | 7 days | |
Secondary | Gene expression | Gene expression of peripheral blood mononuclear cells will be compared between the groups of treatment | 7 days | |
Secondary | Gut microbiome changes | Gut microbiome changes will be compared between the groups of treatment | 7 days | |
Secondary | Epigenetic changes | Epigenetic changes of circulating monocytes will be compared between the groups of treatment | 7 days | |
Secondary | Classification of the immune function | Classification of the immune function of screened patients not characterized with MALS neither with hypo-inflammation | 28 days |
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