Clinical trial NCT02393781: Adrenomedullin and Outcome in Severe Sepsis and Septic Shock
Official title: Adrenomedullin and Outcome in Severe Sepsis and Septic Shock. The AdrenOSS Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Sepsis
Septic Shock
Keywords: severe sepsis
septic shock
adrenomedullin
organ dysfunction
Lead sponsor: Sphingotec GmbH
Sponsor class: INDUSTRY
Collaborators: name: Fondation Transplantation_EDDH
name: Hopital Lariboisière
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
First posted: 2015-03-19
Enrollment: 596
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 600 patients admitted in intensive care unit of 26 hospitals, in 5 countries, with diagnosis of severe sepsis or septic shock, will be included in this study.

Brief summary: The aim of this prospective study is to assess the prognostic value of bioactive plasma adrenomedullin (ADM) in 600 patients with severe sepsis or septic shock in an international multicenter study and to validate the findings concerning the association of ADM concentration and the use of vasopressor therapy, organ failure and outcome.

Detailed description: Sepsis involves an overactive inflammatory response to severe bacterial infection that can compromise vascular integrity and cause tissue edema, organ dysfunction and death. Adrenomedullin (ADM) has attracted the interest of researchers because of its powerful physiological functions. An anti-ADM antibody reduced the norepinephrine infusion rates required to achieve hemodynamic targets, increased urine flow and improved creatinine clearance, which ultimately resulted in attenuated systemic inflammation and tissue apoptosis, during resuscitated cecal ligation and puncture (CLP)-induced septic shock in mice.

In humans, plasma ADM has been determined only in a small number of sepsis patients, and - except from one study - the assays used did not selectively measure the bioactive ADM form and have been considered not reliable. Therefore, the potential value of determining plasma ADM in such patients cannot yet be ascertained and the optimal cut off needs to be validated in future studies

Eligibility criteria: Inclusion Criteria:

* Age \>18 years
* Patients admitted in intensive care unit for severe sepsis or septic shock according to international, standardized criteria,transferred from another intensive care unit less than 24 hours after the primary admission, or being treated with vasopressors for less than 24 hours in the prior ICU
* Signed Consent form

Exclusion Criteria:

* Age \< 18 years
* Severe sepsis or septic shock patients transferred from another intensive care unit later than 24 hours after the primary admission or being treated with vasopressors for more than 24 hours in the prior ICU
* Pregnant women
* Vegetative coma
* Participation in an interventional clinical trial in the preceding month

Primary outcomes:
measure: rate of all-cause mortality
timeFrame: Day 28.
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: La Louvière
country: Belgium
facility: CH Jolimont
city: Ottignies
country: Belgium
facility: Clinique St Pierre
city: Angers
country: France
facility: Centre Hospitalier d'Angers
city: Angoulême
country: France
facility: Centre Hospitalier d'Angoulême
city: Clermont-Ferrand
country: France
facility: Hopital Estaing
city: Colombes
country: France
facility: Hôpital Louis Mourier,
city: La Roche Sur Yon
country: France
facility: CHD de la Vendée
city: Limoges
country: France
facility: CHU Dupuytren
city: Paris
country: France
facility: Hôpital St Louis
city: Paris
country: France
facility: Hôpital Bichat Claude-Bernard
city: Paris
country: France
facility: Hôpital Lariboisière
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Tours
country: France
facility: CHRU Tours
city: Aachen
country: Germany
facility: Klinik für Operative Intensivmedizin und Intermediate Care
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Erfurt
country: Germany
facility: Klinik für Anästhesie, Intensivmedizin und Schmerztherapie, HELIOS-Klinikum Erfurt,
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Köln
country: Germany
facility: Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Köln
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente; Departement of Intensive Care
city: Nijmegen
country: Netherlands
facility: UMC Radboudziekenhuis, Dept. Intensive Care
Study officials:
affiliation: Hôpital Lariboisière, France
name: Alexandre Mebazaa, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinique Universitaire St Luc, Belgique
name: Pierre François Laterre, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jolly L, Carrasco K, Salcedo-Magguilli M, Garaud JJ, Lambden S, van der Poll T, Mebazaa A, Laterre PF, Gibot S, Boufenzer A, Derive M. sTREM-1 is a specific biomarker of TREM-1 pathway activation. Cell Mol Immunol. 2021 Aug;18(8):2054-2056. doi: 10.1038/s41423-021-00733-5. Epub 2021 Jul 19. No abstract available.
citation: Blet A, Deniau B, Santos K, van Lier DPT, Azibani F, Wittebole X, Chousterman BG, Gayat E, Hartmann O, Struck J, Bergmann A, Antonelli M, Beishuizen A, Constantin JM, Damoisel C, Deye N, Di Somma S, Dugernier T, Francois B, Gaudry S, Huberlant V, Lascarrou JB, Marx G, Mercier E, Oueslati H, Pickkers P, Sonneville R, Legrand M, Laterre PF, Mebazaa A; AdrenOSS-1 Study Investigators. Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study. Crit Care. 2021 Feb 15;25(1):61. doi: 10.1186/s13054-021-03471-2.
citation: Mebazaa A, Geven C, Hollinger A, Wittebole X, Chousterman BG, Blet A, Gayat E, Hartmann O, Scigalla P, Struck J, Bergmann A, Antonelli M, Beishuizen A, Constantin JM, Damoisel C, Deye N, Di Somma S, Dugernier T, Francois B, Gaudry S, Huberlant V, Lascarrou JB, Marx G, Mercier E, Oueslati H, Pickkers P, Sonneville R, Legrand M, Laterre PF; AdrenOSS-1 study investigators. Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study. Crit Care. 2018 Dec 21;22(1):354. doi: 10.1186/s13054-018-2243-2.
citation: Hollinger A, Wittebole X, Francois B, Pickkers P, Antonelli M, Gayat E, Chousterman BG, Lascarrou JB, Dugernier T, Di Somma S, Struck J, Bergmann A, Beishuizen A, Constantin JM, Damoisel C, Deye N, Gaudry S, Huberlant V, Marx G, Mercier E, Oueslati H, Hartmann O, Sonneville R, Laterre PF, Mebazaa A, Legrand M. Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study. Kidney Int Rep. 2018 Aug 22;3(6):1424-1433. doi: 10.1016/j.ekir.2018.08.006. eCollection 2018 Nov.