Septic ShockPhase 3Adress-PilotNCT03953677
Evaluation of the Effect of Dexmedetomidine on Phenylephrine Response During Refractory Septic Shock
A Phase 3 study testing Dexmedetomidine 100 Mcg/mL Intravenous Solution and 5% glucose Infusion solution in people with Septic Shock and Vasopressor Resistance, run by Centre Hospitalier Universitaire Dijon at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Vasopressor Resistance
- What is being tested?
- Dexmedetomidine 100 Mcg/mL Intravenous Solution and 5% glucose Infusion solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 27 Oct 2019to 22 Mar 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 12Show fewer
- Catecholamine resistance, defined by the need for a dose of norepinephrine ≥ 0,5 µg/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
Who cannot join
- Cardiac arrest before inclusion and occurring before septic shock criteria are met
- Cardiac index < 2.2 l/min/m² after volume correction, or left ventricular ejection fraction < 40% on echocardiography
- Bradycardia < 55 bpm (apart from treatment with β-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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Pilot Study Evaluating the Effect of Dexmedetomidine on Phenylephrine Response During Refractory Septic Shock
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 α1 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 α2 agonists, usually used for their sedative (dexmedetomidine) or anti-hypertensive (clonidine) effect, normalizes sympathetic activity towards basal values. In animals, α2 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.
- Conditions
- Septic Shock, Vasopressor Resistance
- Being tested
- Dexmedetomidine 100 Mcg/mL Intravenous Solution, 5% glucose Infusion solution
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexmedetomidine 100 Mcg/mL Intravenous SolutionDrug
Continuous infusion of dexmedetomidine at 0.7 µg/kg/h for 2 hours and then 1 µg/kg/h at fixed dose
5% glucose Infusion solutionDrug
Continuous infusion of placebo (5% glucose) at 0.7 µg/kg/h for 2 hours and then 1 µg/kg/h at fixed dose
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Not described Receives: Drug: Dexmedetomidine 100 Mcg/mL Intravenous Solution |
| Placebo | Placebo comparator | Not described Receives: Drug: 5% glucose Infusion solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative change in mean blood pressure, expressed as a percentage
Relative variation in mean blood pressure between the basal value at the beginning of the test and the value reached at the dose of 6 µg/kg/min (%PAM0 = PAMd/PAM0 x100)
Measured: 6 hours after the end of the initial test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start27 Oct 2019
- Primary completion31 Jan 2023
- Study completion22 Mar 2023
Why it stopped: Excess mortality in one arm of the study that led to discontinuation of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire DijonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Dijon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03953677
- Sponsor's protocol ID
- DARGENT APJ 2018
- Acronym
- Adress-Pilot
- Status last verified
- Feb 2026
- First submitted
- 15 May 2019
- Last updated
- 4 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dargent A, Bourredjem A, Jacquier M, Bohe J, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: alpha2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial. Crit Care Med. 2025 Apr 1;53(4):e884-e896. doi: 10.1097/CCM.0000000000006608. Epub 2025 Feb 28.
PubMed 40019329Dargent A, Bourredjem A, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study). Front Med (Lausanne). 2022 Aug 9;9:968274. doi: 10.3389/fmed.2022.968274. eCollection 2022.
PubMed 36017005
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Pilot Study Evaluating the Effect of Dexmedetomidine on Phenylephrine Response During Refractory Septic Shock
- ClinicalTrials.gov ID
- NCT03953677
- Acronym / sponsor ID
- Adress-Pilot / DARGENT APJ 2018
- Conditions
- Septic Shock, Vasopressor Resistance
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Excess mortality in one arm of the study that led to discontinuation of enrollment
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire DijonUniversity, hospital or other
- Study start
- 27 Oct 2019 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 22 Mar 2023 (actual)
- First posted
- 16 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 α1 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 α2 agonists, usually used for their sedative (dexmedetomidine) or anti-hypertensive (clonidine) effect, normalizes sympathetic activity towards basal values. In animals, α2 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: Dexmedetomidine 100 Mcg/mL Intravenous Solution |
| Placebo | Placebo comparator | Drug: 5% glucose Infusion solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 18 years old
- Septic shock, defined by the "Sepsis-3" criteria
- 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 µg/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)
Key exclusion criteria (15 listed)
- Cardiac arrest before inclusion and occurring before septic shock criteria are met
- Cardiac index < 2.2 l/min/m² after volume correction, or left ventricular ejection fraction < 40% on echocardiography
- Bradycardia < 55 bpm (apart from treatment with β-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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexmedetomidine 100 Mcg/mL Intravenous SolutionContinuous infusion of dexmedetomidine at 0.7 µg/kg/h for 2 hours and then 1 µg/kg/h at fixed dose | Drug | Dexmedetomidine |
| 5% glucose Infusion solutionContinuous infusion of placebo (5% glucose) at 0.7 µg/kg/h for 2 hours and then 1 µg/kg/h at fixed dose | Drug | Placebo |
Primary outcome
Relative change in mean blood pressure, expressed as a percentage
Time frame: 6 hours after the end of the initial test
Relative variation in mean blood pressure between the basal value at the beginning of the test and the value reached at the dose of 6 µg/kg/min (%PAM0 = PAMd/PAM0 x100)
Results and safety
The study was stopped early (reason given: Excess mortality in one arm of the study that led to discontinuation of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Results publication: PubMed 40019329Dargent A, Bourredjem A, Jacquier M, Bohe J, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: alpha2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial. Crit Care Med. 2025 Apr 1;53(4):e884-e896. doi: 10.1097/CCM.0000000000006608. Epub 2025 Feb 28.
- Derived from this study: PubMed 36017005Dargent A, Bourredjem A, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study). Front Med (Lausanne). 2022 Aug 9;9:968274. doi: 10.3389/fmed.2022.968274. eCollection 2022.
Related trials for Septic Shock
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexmedetomidine 100 Mcg/mL Intravenous Solution and 5% glucose Infusion solution in people with Septic Shock and Vasopressor Resistance, run by Centre Hospitalier Universitaire Dijon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Excess mortality in one arm of the study that led to discontinuation of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative change in mean blood pressure, expressed as a percentage (time frame: 6 hours after the end of the initial test). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03953677, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.