Efficacy of Dexmedetomidine as Adjunctive Therapy for Refractory Septic Shock in Mechanically Ventilated Patients: A Randomized Controlled Trial
- Trial ID
- 2025-524122-18-00
- Protocol
- 69HCL25 0485
- Sponsor
- Hospices Civils De Lyon
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of dexmedetomidine as an adjunctive treatment for septic shock in mechanically ventilated patients, specifically assessing its impact on 30-day mortality compared to standard care. 5
Secondary objectives include:
- Assessment of 72-hour mortality, ICU mortality, and 90-day mortality.
- Evaluation of hemodynamic parameters, including vasopressor doses at 6, 12, and 24 hours, the rate of rescue therapies, blood pressure changes during the first 24 hours, and the duration of vasopressor dependence over 30 days.
- Monitoring of clinical markers such as lactate clearance, SOFA score evolution at 3 days, daily fluid balance, and resuscitation fluids volume over 5 days.
- Evaluation of clinical outcomes including the duration of mechanical ventilation, incidence of atrial fibrillation, and delayed awakening.
- Assessment of safety and tolerability through the monitoring of bradycardia and ICU delirium.
- Ancillary investigation of sympathetic activity and the renin-angiotensin-aldosterone axis.
Participants
The sponsor did not provide the total number of participants for this study. The study population consists of adult patients, both male and female, experiencing septic shock. Eligible individuals are those undergoing invasive mechanical ventilation and meeting specific physiological parameters, including a SOFA score increase of at least 2 points and persistent hypotension despite adequate fluid resuscitation. The population includes patients exhibiting catecholamine resistance, characterized by a requirement for high-dose vasopressors and persistent circulatory failure. Participants are identified based on clinical indicators such as hyperlactatemia, mottling, or oliguria. This study involves a vulnerable population, requiring specific consent protocols from the patient or a legal representative.
Plans and Procedures
This randomized, controlled trial is designed to evaluate the efficacy of dexmedetomidine as an adjunctive treatment for septic shock. The study focuses on patients experiencing catecholamine resistance while undergoing invasive mechanical ventilation. Following a screening process to confirm eligibility based on Sepsis-3 criteria and specific hemodynamic requirements, participants are randomized to receive either the test intervention or standard care. The primary endpoint is mortality assessed at 30 days post-randomization. Secondary endpoints include vital status at 72 hours and 90 days, vasopressor requirements, mean arterial pressure, lactate levels, SOFA score, and the incidence of atrial fibrillation or ICU delirium. Clinical monitoring includes assessments of bradycardia as a tolerance criterion. The research involves multiple follow-up assessments, including blood and urine sampling for electrolytes and catecholamines at specific hourly and daily intervals. The trial is expected to conclude recruitment by July 2028.
Treatment
The experimental treatment consists of dexmedetomidine administered as a solution for infusion. The dosage is 23.4 µg/kg via intravenous injection.
Background therapies include dobutamine hydrochloride administered at a dose of 0.3 mg/kg through intravenous injection.
Additional background treatments consist of hydrocortisone acetate and lidocaine hydrochloride monohydrate, provided as an intravenous injection at a dose of 200 mg.
Propofol is administered via intravenous injection at a dosage of 2 mg/kg.
Noradrenaline tartrate is utilized as a background therapy at a dose of 7.2 mg/kg via intravenous injection.
Efficacy
The primary efficacy endpoint is vital status at 30 days after randomization. Secondary efficacy parameters include vital status at 72 hours after randomization, as well as at ICU discharge and 90 days after randomization. The assessment of hemodynamic response involves measuring the cumulative dose and peak of vasopressors in norepinephrine equivalent (NEE score) at 6, 12, and 24 hours after randomization. The evolution of mean arterial pressure (MAP) and the MAP/Neq ratio will be evaluated at 0, 6, 12, and 24 hours. Additional efficacy measures include the rate of vasopressin or other rescue therapy use, the number of vasopressor-free days, and the number of mechanical ventilation-free days during the 30-day period following randomization.
Clinical assessments also include lactate level measurements at randomization, 6, 12, and 24 hours, and the SOFA score at Day 0 and Day 3. The difference between total fluid intake and total fluid losses will be monitored from Day 0 to Day 5. The occurrence of new-onset or persistent atrial fibrillation within 14 days post-randomization will be recorded. Furthermore, serum electrolyte panel (Na⁺, K⁺, Cl⁻), plasma measurements of endogenous catecholamines, and plasma assays of the renin–angiotensin system (angiotensin I, angiotensin II, and aldosterone) will be collected at specified timepoints including randomization, 12, 24, 48 hours, and Day 5. Urinary electrolyte panel and urinary measurements of catecholamines and the renin–angiotensin system will be assessed at 24 hours.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 years.
- 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.
- 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).
- Adequate fluid resuscitation: ≥30 ml/kg OR absence of preload dependence criteria (e.g., passive leg raise, pulse pressure variation).
- Patient under invasive mechanical ventilation.
- Patient affiliated with a social security scheme or equivalent.
- 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.
- 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
- Cardiac index <2.2 L/min/m² after volume correction
- Patient participating in another study with an ongoing exclusion period at inclusion
- Pregnant woman (β-HCG ≥5 IU/L) or breastfeeding
- Bradycardia <55 bpm (excluding treatment with β-blockers) or second- or third-degree AV block without pacing
- Moribund patient or those for whom death appears imminent within 24 hours (according to investigator judgment)
- Acute hepatocellular failure with PT and Factor V <50% in the absence of DIC (disseminated intravascular coagulation)
- 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.
- Patient receiving dexmedetomidine prior to randomization
- Patient treated with iproniazid within 15 days prior to randomization
- Patient for whom a decision to limit or withdraw life-sustaining treatments has been made
- Patient under legal protection (guardianship or curatorship) or judicial safeguard
- Contraindications to any of the adjunct medications — norepinephrine, midazolam, propofol, and hydrocortisone — according to their respective SmPCs.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 01 Apr 2026 | 360 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
DEXMÉDÉTOMIDINE VIATRIS 100 microgrammes/mL, solution à diluer pour perfusion | Test | SOLUTION À DILUER POUR PERFUSION | INTRAVENOUS INJECTION | 23.4 | 14 | PRD9896862 |
NOREPINEPHRINE | Other | PHF00230MIG | INTRAVENOUS INJECTION | 7.2 | 14 | SCP124183469 |
MIDAZOLAM | Other | PHF00230MIG | INTRAVENOUS INJECTION | 0.3 | 14 | SCP112629113 |
HYDROCORTISONE | Other | PHF00243MIG | INTRAVENOUS INJECTION | 200 | 14 | SCP101878468 |
PROPOFOL | Other | PHF742 | INTRAVENOUS INJECTION | 2 | 7 | SCP12667971 |