Samu Save Sepsis: Early Goal Directed Therapy in Pre Hospital Care of Patients With Severe Sepsis and/or Septic Shock (SSS)

The purpose of this study is to determine whether an aggressive strategy of severe sepsis patients since pre hospital care, including early antibiotics administration, hemodynamic optimization, and opotherapy when indicated, could reduce mortality

Study Overview

• Status: Completed
• Conditions: Severe Septic Syndrome (Severe Sepsis and Septic Shock) Diagnosed and Treated by Mobile Intensive Care Unit
• Intervention / Treatment: Drug: Ceftriaxone; Drug: Piperacillin tazobactam; Drug: Norepinephrine; Drug: Hydrocortisone

Detailed Description

Major prognostic factor in sepsis management is rapidity of treatments implementation. In 2001, Rivers observed a reduction in mortality through early hemodynamic optimization. In 2009, Arnold emphasizes that establishing more early antibiotic therapy allowed a further reduction of mortality.

In France, pre hospital care is based on mobile intensive care unit (MICU) called SMUR. SMUR is consisting of a driver, a nurse and an emergency physician.

Actually in France, management of severe septic syndrome (severe sepsis and septic shock) are not standardized and based on a "conventional" strategy at the discretion of the emergency physician. Antibiotics are given in only two cases: fulminans purpura and meningitis. Hemodynamic optimization is not a standard of care and no recommendation exist for hemodynamic targets.

An "aggressive" strategy based on early antibiotics administration, hemodynamic optimization and opotherapy when required could be initiated by SMUR since first contact with the patient before hospital admission.

We assume that an "aggressive" strategy initiated during the first 60 minutes of prehospital stage compared to "conventional" strategy could allow to reduce mortality in severe sepsis patients.

• Study Type: Interventional
• Enrollment (Actual): 398
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Anesthesiology, Intensive Care Unit and emergency department - Necker Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All patients fulfilling the following criteria:

• Age ≥ 18 years

• Patient with suspected severe infection defined by the existence of a suspected infection AND

  • Hypotension before vascular fluid loading AND/OR
  • Lactataemia greater than 4 mmol/l AND/OR
  • Glasgow scale lower than 13 AND/OR
  • Mottling score greater than 2
• Patient with a septic shock

Exclusion Criteria:

• Age <18 years or Unable
• Pregnant
• Severe concomitant pathology requiring urgent care(i.e.epilepsy)
• Status "not to be reanimated" life expectancy less than 6 months with no indication of reanimation support ( prior decision on care limitation).
• Fulminans purpura
• True allergy to beta-lactam defined by an angioedema or by an anaphylactic shock during a prior exposure to beta-lactam.
• Patient who have already received hemodynamic optimization or antibiotic treatment before the MICU's (Mobile Intensive Care Unit) care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Conventional; No antibiotic administration and no hemodynamic target are required
Active Comparator: Aggressive; Antibiotics (Ceftriaxone or piperacillin tazobactam) administration, hemodynamic optimization and opotherapy (norepinephrine, hydrocortisone) when required should be performed in the first 60 minutes after contact with the patient	Drug: Ceftriaxone; Ceftriaxone 2g IV will be infused in the first 60 minutes, for non nosocomial severe septic syndrome; Drug: Piperacillin tazobactam; Piperacillin/tazobactam 4g IV will be infused in the first 60 minutes, for nosocomial severe septic syndrome; Drug: Norepinephrine; Norepinephrine will be infused after failure of hemodynamic optimization using vascular fluid loading; Drug: Hydrocortisone; Hydrocortisone 100mg IV will be infused after failure of hemodynamic optimization using norepinephrine with at least 1.5mg/h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of death	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of death	90 days
Number of death	at hospital discharge time, estimated at 90 days
Number of days of stay in intensive care unit	at Intensive Care Unit discharge time, estimated at 90 days
Number of days of stay at hospital	at hospital discharge time, estimated at 90 days
Number of days of vasopressor support	at Intensive Care Unit discharge time, estimated at 90 days
Number of days of mechanical ventilation support	at Intensive Care Unit discharge time, estimated at 90 days
Number of days of renal replacement therapy	at Intensive Care Unit discharge time, estimated at 90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Romain Jouffroy, MD, Anesthesiology, Intensive Care Unit and emergency department - Necker Hospital - 149 rue de Sèvres 75015 Paris - France

Publications and helpful links

General Publications

• Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
• Pottecher T, Calvat S, Dupont H, Durand-Gasselin J, Gerbeaux P; SFAR/SRLF workgroup. Haemodynamic management of severe sepsis: recommendations of the French Intensive Care Societies (SFAR/SRLF) Consensus Conference, 13 October 2005, Paris, France. Crit Care. 2006;10(4):311. doi: 10.1186/cc4965.
• Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
• Sebat F, Johnson D, Musthafa AA, Watnik M, Moore S, Henry K, Saari M. A multidisciplinary community hospital program for early and rapid resuscitation of shock in nontrauma patients. Chest. 2005 May;127(5):1729-43. doi: 10.1378/chest.127.5.1729.
• Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008 Jan;34(1):17-60. doi: 10.1007/s00134-007-0934-2. Epub 2007 Dec 4.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2016
• Primary Completion (Actual): February 9, 2019
• Study Completion (Actual): February 9, 2019

Study Registration Dates

• First Submitted: June 12, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimated): June 16, 2015

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: antibiotics; strategy; Severe septic syndrome; mobile intensive care unit; hemodynamic optimization
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Disease; Sepsis; Toxemia; Shock, Septic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Amides; Amines; Pregnanes; Steroids; Fused-Ring Compounds; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Cephalosporins; Thiazines; Sulfones; Tazobactam; Penicillanic Acid; Piperacillin; Biogenic Monoamines; Biogenic Amines; Catecholamines; Ampicillin; Penicillins; Cefotaxime; Cephacetrile; Piperacillin, Tazobactam Drug Combination; Ceftriaxone; Hydrocortisone; Norepinephrine
• Other Study ID Numbers: 2014-A01030-47

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO