DEXMEDETOMIDINE for Septic shock | Sepsis

Stratification factors

• Centre
• Use of vasopressin at inclusion (Yes/No)
• Type of baseline sedation (propofol yes/no)
• Instantaneous vasopressor dose at randomization (NEE score)
• pH nearest to randomization

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years.\n- Septic shock, defined according to the ‘Sepsis-3’ criteria: Proven or suspected infection, with a SOFA score increase of ≥2 points ; Persistent hypotension requiring vasopressors to maintain a MAP >65 mmHg ; And a serum lactate level >2 mmol/L despite adequate fluid resuscitation.\n- Catecholamine resistance, defined as: The need for an equivalent dose of norepinephrine tartrate ≥0.5 µg/kg/min (according to the NEE vasopressor score, accounting for any concomitant administration of vasopressin, for example) for more than 2 consecutive hours AND Persistent circulatory failure with at least one of the following criteria present within the 2 hours preceding randomization: Hyperlactatemia >2 mmol/L And/or mottling (score ≥1) And/or oliguria (urine output <0.5 ml/kg/h over the last 2 hours).\n- Adequate fluid resuscitation: ≥30 ml/kg OR absence of preload dependence criteria (e.g., passive leg raise, pulse pressure variation).\n- Patient under invasive mechanical ventilation.\n- Patient affiliated with a social security scheme or equivalent.\n- Written consent obtained from the patient (or from the trusted person, family member, or relative if the patient is unable to sign/express consent), or emergency inclusion if the patient is unable to provide consent and neither the trusted person nor any family member or relative is present at the time of inclusion. In the context of refractory shock, the proposed therapeutic intervention cannot be delayed by more than one hour.\n- Continuation consent obtained from the patient as soon as they are able to provide consent (in cases where consent was initially signed by the trusted person, a family member, or a relative at inclusion) and, in the case of emergency inclusion: continuation consent from the relative obtained as soon as possible (if the trusted person, a family member, or a relative arrives at the hospital while the patient is still unable to consent)."}

Exclusion criteria

• {"criterion_text":"- Cardiac index <2.2 L/min/m² after volume correction\n- Patient for whom a decision to limit or withdraw life-sustaining treatments has been made\n- Patient under legal protection (guardianship or curatorship) or judicial safeguard\n- Contraindications to any of the adjunct medications — norepinephrine, midazolam, propofol, and hydrocortisone — according to their respective SmPCs.\n- Patient participating in another study with an ongoing exclusion period at inclusion\n- Pregnant woman (β-HCG ≥5 IU/L) or breastfeeding\n- Bradycardia <55 bpm (excluding treatment with β-blockers) or second- or third-degree AV block without pacing\n- Moribund patient or those for whom death appears imminent within 24 hours (according to investigator judgment)\n- Acute hepatocellular failure with PT and Factor V <50% in the absence of DIC (disseminated intravascular coagulation)\n- Contraindications to dexmedetomidine: Known hypersensitivity to dexmedetomidine or to any of its excipients, advanced heart block (grade 2 or 3) unless a pacemaker is present, uncontrolled hypotension, acute cerebrovascular conditions.\n- Patient receiving dexmedetomidine prior to randomization\n- Patient treated with iproniazid within 15 days prior to randomization"}

Primary endpoints

• {"endpoint_text":"- Vital status at 30 days after randomization (Day 30).","definition_or_measurement_approach":"Vital status (alive/dead) assessed at 30 days after randomization (Day 30)."}

Secondary endpoints

• {"endpoint_text":"- Efficacy criteria: Vital status at 72 hours after randomization.","definition_or_measurement_approach":"Vital status (alive/dead) assessed at 72 hours after randomization."}
• {"endpoint_text":"- Efficacy criteria: Cumulative dose and peak of vasopressors in norepinephrine equivalent (NEE score, Kotani et al. 2023) at 6h, 12h, and 24h after randomization.","definition_or_measurement_approach":"Cumulative vasopressor dose and peak vasopressor dose expressed as norepinephrine equivalents (NEE score) at H+6, H+12 and H+24 post-randomization."}
• {"endpoint_text":"- Efficacy criteria: Rate of use of vasopressin (VP) or other rescue therapies during the 30 days following randomization (Day 0 → Day 30).","definition_or_measurement_approach":"Proportion of patients receiving vasopressin or other rescue therapies during Day 0 to Day 30 after randomization."}
• {"endpoint_text":"- Efficacy criteria: Evolution of mean arterial pressure (MAP) and MAP/Neq ratio (Neq = norepinephrine equivalent) within the first 24 hours after randomization (H0, H+6, H+12, H+24).","definition_or_measurement_approach":"Serial measurements of MAP and MAP/Neq ratio at randomization (H0), H+6, H+12 and H+24."}
• {"endpoint_text":"- Efficacy criteria: Number of vasopressor-free days during the 30 days following randomization (Day 0 → Day 30).","definition_or_measurement_approach":"Count of days without vasopressor support during Day 0 to Day 30 post-randomization."}
• {"endpoint_text":"- Efficacy criteria: Number of mechanical ventilation–free days during the 30 days following randomization (Day 0 → Day 30).","definition_or_measurement_approach":"Count of days without invasive mechanical ventilation during Day 0 to Day 30 post-randomization."}
• {"endpoint_text":"- Efficacy Criteria: Lactate level at randomization, then at H+6, H+12, and H+24.","definition_or_measurement_approach":"Serum lactate measured at randomization (H0) and at H+6, H+12, H+24."}
• {"endpoint_text":"- Efficacy Criteria: SOFA score at Day 0 and Day 3 after randomization.","definition_or_measurement_approach":"SOFA score assessed at Day 0 (randomization) and Day 3 post-randomization."}
• {"endpoint_text":"- Efficacy Criteria: Difference between total fluid intake (including IV infusions, enteral nutrition, blood products, flushes, and diluents) and total fluid losses (including urine output, drain outputs, and gastric tube losses) over 6 days (from Day 0 to Day 5).","definition_or_measurement_approach":"Net fluid balance calculated as total inputs minus total outputs from Day 0 to Day 5."}
• {"endpoint_text":"- Efficacy Criteria: Occurrence of new-onset or persistent atrial fibrillation within 14 days following randomization.","definition_or_measurement_approach":"Incidence of new-onset or persistent atrial fibrillation within 14 days post-randomization, assessed clinically/ECG."}
• {"endpoint_text":"- Efficacy Criteria: Vital status at ICU discharge and at 90 days after randomization.","definition_or_measurement_approach":"Vital status (alive/dead) assessed at ICU discharge and at Day 90 post-randomization."}
• {"endpoint_text":"- Tolerance Criteria: Occurrence of bradycardia during the treatment period: heart rate (HR) < 50 bpm requiring therapeutic intervention (discontinuation of dexmedetomidine due to bradycardia, administration of atropine, adrenaline, isoprenaline, or external electrical pacing).","definition_or_measurement_approach":"Number/proportion of patients with HR <50 bpm requiring specified therapeutic interventions during treatment period."}
• {"endpoint_text":"- Tolerance Criteria: Number of coma-free days at Day 30 (or at ICU discharge if discharged before Day 30), defined as the number of days with a RASS score ≥ -3.","definition_or_measurement_approach":"Count of days with RASS ≥ -3 up to Day 30 or until ICU discharge."}
• {"endpoint_text":"- Tolerance Criteria: Occurrence of ICU delirium during the stay, screened daily using the CAM-ICU score (Appendix 2) until Day 30 (or ICU discharge if discharged before Day 30) in patients with a RASS score (Appendix 2) ≥ -3.","definition_or_measurement_approach":"Daily CAM-ICU screening to identify incident ICU delirium up to Day 30 or ICU discharge in eligible patients (RASS ≥ -3)."}
• {"endpoint_text":"- Ancillary Study Criteria: Serum electrolyte panel (Na⁺, K⁺, Cl⁻) at H0 (randomization), H+12, H+24, H+48, and Day 5; plasma measurements of endogenous catecholamines and plasma assays of the renin–angiotensin system (angiotensin I and II, aldosterone) at H0 (randomization), H+12, H+48, and Day 5. Urinary electrolyte panel (Na⁺, K⁺, Cl⁻) and urinary measurements of endogenous catecholamines and the renin–angiotensin system (angiotensin I and II, aldosterone) at H+24.","definition_or_measurement_approach":"Ancillary biochemical and hormonal assays at specified time points (serum and urine electrolytes; plasma and urinary catecholamines and renin–angiotensin system markers) as listed."}

France

Earliest CTIS Part Ii Submission Date

19-03-2026

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

41

Number Of Sites

18

Number Of Participants

360

Primary sponsor

Full Name

Hospices Civils De Lyon

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"DGOS","duties_or_roles":"Source of monetary support","organisation_type":""}