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NCT Number: NCT07179276

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

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.

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Key information

Conditions

Sepsis - to Reduce Mortality in the Intensive Care Unit Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Septic Shock Shock Shock, Septic Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHu Angers, Angers, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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
  • 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

Treatment and study plan

CO2gap-guided resuscitation strategy

Procedure

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).

Primary outcomes

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

    Time frame: Every day until Day 28

Secondary outcomes

  1. Key secondary endpoints

    Time frame: Every day until Day 28

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

  2. Key secondary endpoints

    Time frame: Every day until Day 90

    All-cause mortality at Day 90

  3. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

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

  4. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

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

  5. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

    Mechanical ventilation-free days up to Day 28

  6. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

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

  7. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

    Duration of mechanical ventilation up to Day 28

  8. Secondary Efficacy Endpoints

    Time frame: Every day until Day 7

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

  9. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

    ICU-free days up to Day 28

  10. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

    ICU length of stay up to Day 28

  11. Secondary Efficacy Endpoints

    Time frame: Every day until Day 28

    Hospital length of stay up to Day 28

  12. Secondary Efficacy Endpoints

    Time frame: At Day 90 after randomization

    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.

  13. Secondary Safety Endpoints

    Time frame: Every day until Day 28

    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

Study contacts

Contact information is provided by the study sponsor or research team.

Lise Laclautre

CONTACT

[email protected]

0473754963

Sponsors and collaborators

Lead sponsor

University Hospital, Clermont-Ferrand

Other

Registry information

Official study title

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

Acronym: CARBON

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Sep 17, 2025
Registry last updated
Jun 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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