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

NCT07179276 | Recruiting

• 1 other identifier: PHRC N 2020 FUTIER
• Study Type: interventional
• Target: 750
• Locations: 1 country
• Sites: 28

Brief 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. 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.

Conditions

Septic Shock; Sepsis - to Reduce Mortality in the Intensive Care Unit

Keywords

lactate; CO2 gap; resuscitation strategie; sepsis; hemodynamic therapy

Outcome Measures

Primary Outcomes (1)

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

  Every day until Day 28

Secondary Outcomes (13)

• Key secondary endpoints

  Every day until Day 28

• Key secondary endpoints

  Every day until Day 90

• Secondary Efficacy Endpoints

  Every day until Day 28

• Secondary Efficacy Endpoints

  Every day until Day 28

• Secondary Efficacy Endpoints

  Every day until Day 28

Study Arms (2)

CO2gap-guided resuscitation strategy

EXPERIMENTAL

CO2gap-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

Procedure: CO2gap-guided resuscitation strategy

Lactate level-guided resuscitation strategy

NO INTERVENTION

Lactate 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.

Interventions

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).

CO2gap-guided resuscitation strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (28)

CHu Angers

Angers, France

NOT YET RECRUITING

CH Aurillac

Aurillac, France

NOT YET RECRUITING

CH de la Côte Basque

Bayonne, France

RECRUITING

CHU Bordeaux Hôpital Haut Lévèque

Bordeaux, France

RECRUITING

CHU Bordeaux Pellegrin Hospital

Bordeaux, France

RECRUITING

CHU Clermont-Ferrand Estaing

Clermont-Ferrand, France

RECRUITING

CHU Clermont-Ferrand Gabriel Montpied

Clermont-Ferrand, France

RECRUITING

CHU Dijon

Dijon, France

RECRUITING

CHU Grenoble

Grenoble, France

NOT YET RECRUITING

CH Le puy en Velay

Le Puy-en-Velay, France

RECRUITING

HCL - Lyon Sud

Lyon, France

NOT YET RECRUITING

HCL Hôpital Edouard Herriot

Lyon, France

NOT YET RECRUITING

AP HM Hôpital la Timone

Marseille, France

RECRUITING

CHU Montpellier

Montpellier, France

RECRUITING

CH Moulins-Yzeure

Moulins, France

NOT YET RECRUITING

CHU Nantes

Nantes, France

RECRUITING

CHU Nîmes

Nîmes, France

NOT YET RECRUITING

APHP Beaujon

Paris, France

RECRUITING

APHP Bicêtre

Paris, France

RECRUITING

APHP La pitié Salpêtrière - Anesthésie et soin intensif

Paris, France

RECRUITING

APHP Lariboisière

Paris, France

RECRUITING

CHU la pitié slapêtrière - Anesthésie Réanimation

Paris, France

RECRUITING

CHU Poitiers

Poitiers, France

RECRUITING

CHU Rennes

Rennes, France

RECRUITING

CHRU Strasbourg - Service d'anesthésie-Réanimation médicale

Strasbourg, France

RECRUITING

CHU Strasbourg Service d'Anesthésie-Réanimation chirurgicale

Strasbourg, France

RECRUITING

Chu Toulouse

Toulouse, France

RECRUITING

CH Vichy

Vichy, France

NOT YET RECRUITING

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Related Links

• How Can We Use Tissue Carbon Dioxide Measurement as an Index of Perfusion? E. Futier, J.-L. Teboul, and B. Vallet

MeSH Terms

Conditions

Shock, Septic; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Central Study Contacts

Lise Laclautre

CONTACT

0473754963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Data will be collected and entered into the electronic web-based case report form by trial or clinical trained personal blinded to the allocation group. Statistical analyses will be performed with the statistician blinded to the allocation group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 17, 2025
• Study Start: March 29, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (28)