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Sepsis - to Reduce Mortality in the Intensive Care UnitCARBONNCT07179276

Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock

A study testing CO2gap-guided resuscitation strategy in people with Sepsis - to Reduce Mortality in the Intensive Care Unit and Septic Shock, run by University Hospital, Clermont-Ferrand at 28 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction and represents a major healthcare problem. Septic shock is the most severe form, characterized by increased capillary permeability and vasodilation, resulting in hypotension and tissue hypoxia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CO2gap-guided resuscitation strategy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
750 participants
Where
28 sitesFrance
Study dates
29 Mar 2026to 31 Dec 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged 18 years or older AND
  • Acutely admitted to a study ICU AND
  • Primary diagnosis of septic shock according to the Sepsis-3 criteria and defined as:
  • A suspected or documented site of infection or positive blood culture AND
  • Acute increase of at least 2 points in the Sequential Organ Failure Assessment (SOFA) score consequent to the infection AND
  • Having a serum lactate level >2 mmol/l AND
  • Requirement of vasopressors (any dose of norepinephrine) to maintain mean arterial pressure (MAP) ≥65 mmHg despite adequate fluid resuscitation (at least 1L of IV fluid in the last 24 hours prior to screening)

Who cannot join

  • Septic shock for more than 12 hours at the time of screening
  • Primary cause of hypotension not due to sepsis (e.g., acute bleeding)
  • Decision not to resuscitate (or to limit full care) or not to intubate taken before obtaining consent
  • Death is deemed to be imminent or inevitable or patients with an underlying disease process with a life expectancy of less than 3 months
  • Anticipated surgery during the first 24 hours after randomization
  • Patient or their relatives' refusal to participate
Show all 11Show fewer
  • Patients participating in another RCT with interventions possibly compromising the primary outcome
  • Prior enrollment in the CARBON trial
  • Known to be pregnant.
  • Legal protection (i.e., incompetence to provide consent and no guardian or incarceration)
  • No affiliation with the French health care system

Trial locations and contacts

28 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Lise Laclautre contact

0473754963

promo_interne_drci@chu-clermontferrand.fr

28 sites in 1 country

France28 sites, 28 recruiting

  • CHu Angers

    Angers

    Sigismond Lasocki

    Not yet recruiting

  • CH Aurillac

    Aurillac

    Emanuele TURBIL

    Not yet recruiting

  • CH de la Côte Basque

    Bayonne

    Hadrien ROZE

    Recruiting

  • CHU Bordeaux Hôpital Haut Lévèque

    Bordeaux

    Antoine DEWITTE

    Recruiting

  • CHU Bordeaux Pellegrin Hospital

    Bordeaux

    Matthieu BIAIS

    Recruiting

  • CHU Clermont-Ferrand Estaing

    Clermont-Ferrand

    Lise Laclautre, 0473754963, promo_interne_drci@chu-clermontferrand.fr

    Emmanuel FUTIER

    Recruiting

  • CHU Clermont-Ferrand Gabriel Montpied

    Clermont-Ferrand

    Lise Laclautre, 0473754963, promo_interne_drci@chu-clermontferrand.fr

    Thomas GODET

    Recruiting

  • CHU Dijon

    Dijon

    Grégoire GUINOT

    Recruiting

  • CHU Grenoble

    Grenoble

    Marie Christine HERAULT

    Not yet recruiting

  • CH Le puy en Velay

    Le Puy-en-Velay

    Rémi ESPENEL

    Recruiting

  • HCL - Lyon Sud

    Lyon

    Romain FORT

    Not yet recruiting

  • HCL Hôpital Edouard Herriot

    Lyon

    Anne Claire LUKASZEWICZ

    Not yet recruiting

  • AP HM Hôpital la Timone

    Marseille

    Pierre SIMEONE

    Recruiting

  • CHU Montpellier

    Montpellier

    Samir JABER

    Recruiting

  • CH Moulins-Yzeure

    Moulins

    Pierre-antoine PIOCHE

    Not yet recruiting

  • CHU Nantes

    Nantes

    Paul ROOZE

    Recruiting

  • CHU Nîmes

    Nîmes

    Claire Roger

    Not yet recruiting

  • APHP Beaujon

    Paris

    Emmanuel WEISS

    Recruiting

  • APHP Bicêtre

    Paris

    Benjamin BERGIS

    Recruiting

  • APHP La pitié Salpêtrière - Anesthésie et soin intensif

    Paris

    Fanny VARDON

    Recruiting

  • APHP Lariboisière

    Paris

    Maxime COUTROT

    Recruiting

  • CHU la pitié slapêtrière - Anesthésie Réanimation

    Paris

    Constantin Jean Michel

    Recruiting

  • CHU Poitiers

    Poitiers

    Quentin SAINT GENIS

    Recruiting

  • CHU Rennes

    Rennes

    Yoann LAUNEY

    Recruiting

  • CHRU Strasbourg - Service d'anesthésie-Réanimation médicale

    Strasbourg

    Olivier COLLANGE

    Recruiting

  • CHU Strasbourg Service d'Anesthésie-Réanimation chirurgicale

    Strasbourg

    Julien POTTERCHER

    Recruiting

  • Chu Toulouse

    Toulouse

    Fanny VARDON

    Recruiting

  • CH Vichy

    Vichy

    Loic DOPEUX

    Not yet recruiting

Other trials in France

About this study

Official title: Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock: A Multicenter Prospective Randomized Trial (CARBON)

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction and represents a major healthcare problem. Septic shock is the most severe form, characterized by increased capillary permeability and vasodilation, resulting in hypotension and tissue hypoxia. Early identification and treatment of tissue hypoperfusion are pivotal components of initial resuscitation to limit progression to multiple organ dysfunction and death. The 2021 Surviving Sepsis Guidelines recommend guiding initial resuscitation by targeting decreases in serum lactate levels in patients with elevated lactate. However, although elevated lactate levels may reflect tissue hypoxia, serum lactate is not a direct marker of tissue perfusion. Hyperlactatemia may be attributable to mechanisms other than tissue hypoperfusion, such as accelerated aerobic glycolysis driven by excessive β-adrenergic stimulation or impaired clearance (e.g., in liver failure).

The venous-to-arterial carbon dioxide partial pressure difference (CO₂ gap), which is inversely related to cardiac output, has been shown to reflect the adequacy of venous blood flow to remove CO₂ from tissues. The CO₂ gap is closely linked to microcirculatory blood flow during the early resuscitation phase of septic shock and may effectively identify persistent tissue hypoperfusion in shock states. A persistently high CO₂ gap during early resuscitation has been associated with significantly higher 28-day mortality and increased Sequential Organ Failure Assessment (SOFA) scores. Moreover, the CO₂ gap has been shown to respond to changes in cardiac output during inotrope infusion in patients with low blood flow, suggesting that its assessment could be useful for therapeutic adjustments. Therefore, there are compelling arguments to evaluate the usefulness of the CO₂ gap in guiding early resuscitation in patients with septic shock.

The investigators postulated that CO₂ gap-guided early resuscitation may be more effective in improving outcomes than lactate-guided resuscitation.

Read the detailed description

Main objective: The aim of the CARBON trial is to compare a veno-arterial CO2 difference-guided resuscitation strategy (CO2gap-guided strategy) with a lactate level-guided resuscitation on mortality in adults intensive care unit (ICU) patients fulfilling the SEPSIS-3 criteria consensus definition.

HYPOTHESIS: The investigators hypothesized that a CO2gap-guided resuscitation strategy during early septic shock would reduce mortality compared with a lactate level-guided resuscitation.

Being tested
CO2gap-guided resuscitation strategy
Keywords
lactate, CO2 gap, resuscitation strategie, sepsis, hemodynamic therapy
Medical subject headings
Shock, Septic, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CO2gap-guided resuscitation strategyProcedure or surgery

    For patients assigned to the interventional arm, adherence to the algorithm will complement clinical practices in the following areas:

    • Blood sampling for venous blood gas analysis. Blood samples will be taken from an existing central venous catheter; central venous access is common clinical practice in critically ill patients.
    • The use of dobutamine and blood transfusions in patients showing signs of oxygen deficiency (both will be carried out in accordance with the intended use and conditions of current practice).
Study groups in NCT07179276
Study groupRoleWhat they receive
CO2gap-guided resuscitation strategyExperimentalCO2gap-guided resuscitation strategy aimed at maintaining central venous-to-arterial CO2 partial pressure difference (CO2gap) lower than 6 mmHg, using a sequential approach through a dedicated hemodynamic algorithm. Arterial and central venous blood samples will be drawn simultaneously and reassessed at 2 to 4-hour intervals
Receives: Procedure: CO2gap-guided resuscitation strategy
Lactate level-guided resuscitation strategyNo interventionLactate level-guided resuscitation strategy aimed at normalizing or decreasing lactate levels by 20% at 2 to 4-hour intervals, as per the surviving sepsis campaign guidelines.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The primary end point is all-cause mortality at 28 days after randomization

    Measured: Every day until Day 28

Secondary outcomes (13)

  1. Key secondary endpoints

    Duration of septic shock (i.e., vasopressor use) up to Day 28

    Measured: Every day until Day 28

  2. Key secondary endpoints

    All-cause mortality at Day 90

    Measured: Every day until Day 90

  3. Secondary Efficacy Endpoints

    Vasopressor-free and inotrope-free days up to Day 28

    Measured: Every day until Day 28

  4. Secondary Efficacy Endpoints

    Renal replacement therapy-free days (excluding patients on renal replacement therapy at time of randomization) up to Day 28

    Measured: Every day until Day 28

  5. Secondary Efficacy Endpoints

    Mechanical ventilation-free days up to Day 28

    Measured: Every day until Day 28

  6. Secondary Efficacy Endpoints

    Duration of renal replacement therapy (excluding patients on renal replacement therapy at time of randomization) up to Day 28

    Measured: Every day until Day 28

  7. Secondary Efficacy Endpoints

    Duration of mechanical ventilation up to Day 28

    Measured: Every day until Day 28

  8. Secondary Efficacy Endpoints

    Incidence of new organ dysfunction (based on the SOFA score) up to Day 7

    Measured: Every day until Day 7

  9. Secondary Efficacy Endpoints

    ICU-free days up to Day 28

    Measured: Every day until Day 28

  10. Secondary Efficacy Endpoints

    ICU length of stay up to Day 28

    Measured: Every day until Day 28

  11. Secondary Efficacy Endpoints

    Hospital length of stay up to Day 28

    Measured: Every day until Day 28

  12. Secondary Efficacy Endpoints

    EuroQol 5 Dimensions, 5 Levels (EQ-5D-5L) :a measure of health-related quality of life at Day 90:

    The EQ-5D-5L score is analyzed using the utility value (global index score).

    In France, the score ranges from about -0.53 (health states considered worse than death) to 1.00 (full health).

    0.00 corresponds to a health state equivalent to death.

    Measured: At Day 90 after randomization

  13. Secondary Safety Endpoints

    Incidence of adverse events with specific emphasis on the incidence of ischemic (e.g., myocardial, stroke, intestinal, limb ischemia) and arrhythmia (excluding sinus tachycardia or sinus arrhythmia) events reported as having a reasonable possibility of a causal relationship with the study procedures

    Measured: Every day until Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2025
  2. Study start29 Mar 2026
  3. Primary completion30 Nov 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
750 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07179276
Sponsor's protocol ID
PHRC N 2020 FUTIER
Acronym
CARBON
Status last verified
Jun 2026
First submitted
11 Sep 2025
Last updated
15 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993 Dec 22-29;270(24):2957-63. doi: 10.1001/jama.270.24.2957.

    PubMed 8254858

  • Levey AS, Becker C, Inker LA. Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. JAMA. 2015 Feb 24;313(8):837-46. doi: 10.1001/jama.2015.0602.

    PubMed 25710660

  • Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.

    PubMed 8844239

  • Laterre PF, Berry SM, Blemings A, Carlsen JE, Francois B, Graves T, Jacobsen K, Lewis RJ, Opal SM, Perner A, Pickkers P, Russell JA, Windelov NA, Yealy DM, Asfar P, Bestle MH, Muller G, Bruel C, Brule N, Decruyenaere J, Dive AM, Dugernier T, Krell K, Lefrant JY, Megarbane B, Mercier E, Mira JP, Quenot JP, Rasmussen BS, Thorsen-Meyer HC, Vander Laenen M, Vang ML, Vignon P, Vinatier I, Wichmann S, Wittebole X, Kjolbye AL, Angus DC; SEPSIS-ACT Investigators. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial. JAMA. 2019 Oct 15;322(15):1476-1485. doi: 10.1001/jama.2019.14607.

    PubMed 31577035

  • STARRT-AKI Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group; United Kingdom Critical Care Research Group; Canadian Nephrology Trials Network; Irish Critical Care Trials Group; Bagshaw SM, Wald R, Adhikari NKJ, Bellomo R, da Costa BR, Dreyfuss D, Du B, Gallagher MP, Gaudry S, Hoste EA, Lamontagne F, Joannidis M, Landoni G, Liu KD, McAuley DF, McGuinness SP, Neyra JA, Nichol AD, Ostermann M, Palevsky PM, Pettila V, Quenot JP, Qiu H, Rochwerg B, Schneider AG, Smith OM, Thome F, Thorpe KE, Vaara S, Weir M, Wang AY, Young P, Zarbock A. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020 Jul 16;383(3):240-251. doi: 10.1056/NEJMoa2000741.

    PubMed 32668114

  • Fergusson D, Aaron SD, Guyatt G, Hebert P. Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ. 2002 Sep 21;325(7365):652-4. doi: 10.1136/bmj.325.7365.652. No abstract available.

    PubMed 12242181

  • Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994 Jun 16;330(24):1717-22. doi: 10.1056/NEJM199406163302404.

    PubMed 7993413

  • Deis AS, Whiles BB, Brown AR, Satterwhite CL, Simpson SQ. Three-Hour Bundle Compliance and Outcomes in Patients With Undiagnosed Severe Sepsis. Chest. 2018 Jan;153(1):39-45. doi: 10.1016/j.chest.2017.09.031. Epub 2017 Oct 5.

    PubMed 28987477

  • Pruinelli L, Westra BL, Yadav P, Hoff A, Steinbach M, Kumar V, Delaney CW, Simon G. Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2018 Apr;46(4):500-505. doi: 10.1097/CCM.0000000000002949.

    PubMed 29298189

  • Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, Lemeshow S, Osborn T, Terry KM, Levy MM. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017 Jun 8;376(23):2235-2244. doi: 10.1056/NEJMoa1703058. Epub 2017 May 21.

    PubMed 28528569

  • Creteur J, De Backer D, Vincent JL. A dobutamine test can disclose hepatosplanchnic hypoperfusion in septic patients. Am J Respir Crit Care Med. 1999 Sep;160(3):839-45. doi: 10.1164/ajrccm.160.3.9807029.

    PubMed 10471606

  • Teboul JL, Mercat A, Lenique F, Berton C, Richard C. Value of the venous-arterial PCO2 gradient to reflect the oxygen supply to demand in humans: effects of dobutamine. Crit Care Med. 1998 Jun;26(6):1007-10. doi: 10.1097/00003246-199806000-00017.

    PubMed 9635647

  • Mallat J, Pepy F, Lemyze M, Gasan G, Vangrunderbeeck N, Tronchon L, Vallet B, Thevenin D. Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock: a prospective observational study. Eur J Anaesthesiol. 2014 Jul;31(7):371-80. doi: 10.1097/EJA.0000000000000064.

    PubMed 24625464

  • Vallee F, Vallet B, Mathe O, Parraguette J, Mari A, Silva S, Samii K, Fourcade O, Genestal M. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med. 2008 Dec;34(12):2218-25. doi: 10.1007/s00134-008-1199-0. Epub 2008 Jul 8.

    PubMed 18607565

  • De Backer D. Detailing the cardiovascular profile in shock patients. Crit Care. 2017 Dec 28;21(Suppl 3):311. doi: 10.1186/s13054-017-1908-6.

    PubMed 29297372

Questions about this trial

What is this clinical trial studying?

A study testing CO2gap-guided resuscitation strategy in people with Sepsis - to Reduce Mortality in the Intensive Care Unit and Septic Shock, run by University Hospital, Clermont-Ferrand at 28 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lise Laclautre (0473754963, promo_interne_drci@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The primary end point is all-cause mortality at 28 days after randomization (time frame: Every day until Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07179276, which also lists 49 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.

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