Evaluation of the Effect of Dexmedetomidine on Phenylephrine Response During Refractory Septic Shock (Adress-Pilot)

  • End date
    Jul 6, 2023
  • participants needed
  • sponsor
    Centre Hospitalier Universitaire Dijon
Updated on 16 February 2022
lactic acid
mechanical ventilation
organ failure
lactate level
increase blood pressure


Septic shock is common in patients admitted to intensive care and hospital mortality occurs in close to 50% of these patients. In half of the cases, death occurs within the first 72 hours in a context of multiple organ failure that does not respond to conventional therapies, particularly circulatory therapies, despite increasing doses of catecholamines. Vasopressor resistance in septic patients defines refractory septic shock. In one study (Conrad et al. 2015), the increase in blood pressure observed with an infusion of increasing doses of phenylephrine (dose-response curve) made it possible to quickly and clearly identify patients resistant to vasopressors at a high risk of death by refractory shock (ROC AUC 0.92). This resistance is due in particular to a downregulation of 1 adrenergic receptors, linked to sympathetic hyper activation associated with septic shock. To date, there is no validated therapy in this situation. However, experimental data have shown that the administration of 2 agonists, usually used for their sedative (dexmedetomidine) or anti-hypertensive (clonidine) effect, normalizes sympathetic activity towards basal values. In animals, 2 agonists restore the sensitivity of alpha1 adrenergic receptors, resulting in improved vasopressor sensitivity and survival. In humans, a beneficial effect on mortality was suggested in the first trial testing dexmedetomidine in septic patients in 2017. This effect was observed especially in the most severe patients, suggesting a restoration of sensitivity to vasopressors.

The hypothesis is that the administration of dexmedetomidine in patients in refractory septic shock may improve response to phenylephrine and decrease resistance to vasopressors. This pilot study could lay the foundation for a randomized controlled trial.

Condition Septic Shock, Vasopressor Resistance
Treatment Dexmedetomidine 100 Mcg/mL Intravenous Solution, 5% glucose Infusion solution
Clinical Study IdentifierNCT03953677
SponsorCentre Hospitalier Universitaire Dijon
Last Modified on16 February 2022


Yes No Not Sure

Inclusion Criteria

Age 18 years old
Septic shock, defined by the "Sepsis-3" criteria
proven or suspected infection, with modification of the SOFA score 2 points
with persistent hypotension requiring vasopressors to maintain MAP 65 mmHg
and a serum lactate level > 2 mmol/L despite adequate vascular filling
Adequate vascular filling: 30ml/kg, OR absence of preload-dependency criteria at time of assessment (respiratory variability of the inferior vena cava, passive leg lift, pulsed pressure variation)
Catecholamine resistance, defined by the need for a dose of norepinephrine 0,5 g/kg/min for more than 2 consecutive hours within 24 hours of admission to intensive care unit
persistence of circulatory failure with at least one of the following criteria present in the 2 hours prior to randomisation: hyperlactatemia > 2mmol/l, and/or mottling ( 1 score), and/or oliguria (diuresis < 0,5 ml/kg/h over the last 2 hours)
Invasive Mechanical ventilation
Under sedation by midazolam or propofol
Informed consent obtained from a relative for patient included in an emergency
Patient affiliated to the national health insurance system

Exclusion Criteria

Cardiac arrest before inclusion and occurring before septic shock criteria are met
Cardiac index < 2.2 l/min/m after volume correction, or left ventricular ejection fraction < 40% on echocardiography
Bradycardia < 55 bpm (apart from treatment with -blocker) or 2nd or 3rd degree BAV not equipped
Proven or suspected decompensation of coronary heart disease
Acute cerebrovascular condition within 2 weeks prior to inclusion
Severe hepatic insufficiency with TP and factor V <50% in the absence of DIC (disseminated intravascular coagulation)
Patient on adrenaline or vasopressors at the time of inclusion (epinephrine or vasopressin stopped prior to inclusion is not a criterion for non-inclusion)
Patient on non-selective MAOI iproniazid within 15 days of inclusion
Patient for whom a decision has been made to limit the use of therapies
Hypersensitivity to dexmedetomidine or phenylephrine
Patient on dexmedetomidine before inclusion
Person subject to a legal protection measure (curatorship, guardianship)
Person subject to limited judicial protection
Pregnant, parturient or breastfeeding woman
Patient with suspected or confirmed mesenteric ischemia
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note