Septic ShockPhase 3MILANOSNCT04931225
LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)
A Phase 3 study testing Landiolol in people with Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in Heart Rate (HR) on microcirculatory vascular reactivity vs. usual tachycardia management and evaluate the hemodynamic effects of Landiolol vs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Landiolol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteFrance
- Study dates
- 18 Jul 2022to Jul 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Sinus tachycardia not compensatory, if the doctor considers that the heart rate acceleration should be treated.
- The study will be carried out in
- reanimated and stabilized septic shock defined as:
- Septic shock is tachycardic (HR>100/min) patients with sepsis (suspected infection + 2 SOFA points) according to the latest international definition and the need to receive noradrenaline to maintain an average blood pressure above 65 mmHg
- Patient supported for at least 6 hours, necessary for diagnostic management and hemodynamic optimization according to international standards and for less than 24 hours to limit confounding factors related to prolonged reanimation (sedation) and empowerment of organ failure in general and vascular in particular. Hemodynamic stabilization will be defined as the absence of increased doses of norepinephrine in the previous two hours to limit the risk of hypotension induced by Landiolol infusion.
- Age >18 years
- Patient (or family member) informed consent signature or emergency consent
- Affiliation to a social security system
Who cannot join
- Asthma
- Patients treated with the following bradycardizing drugs:
- Digitalis
- Bradycardizing calcium channel blockers
- Cordarone
- Other beta-blocker
Show all 15Show fewer
- Hypersensitivity to Landiolol or to one of its excipients (Mannitol E421, sodium hydroxide)
- Sinus disease
- Cardiogenic shock
- Decompensated heart failure when considered unrelated to arrhythmia
- Pregnant or nursing woman,
- Participation in another interventional research involving the human person or being in the exclusion period following a previous research involving the human person, if applicable
- Ward or curative patient
- Moribund patient
- Estimated life expectancy less than 1 month
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Intensive care department, Hôpital Saint Antoine
Paris, 75012
Hafid AIT-OUFELLA, Professor, 01 49 28 23 15, hafid.aitoufella@aphp.fr
About this study
Official title: LANdiolol MIcrocirculatory Effects During Septic chOc
The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in Heart Rate (HR) on microcirculatory vascular reactivity vs. usual tachycardia management and evaluate the hemodynamic effects of Landiolol vs. usual management in patients with septic shock.
Read the detailed description
This is a Phase 3, prospective, randomized, open label, evaluation of the efficacy of continuous intravenous Landiolol injection up to a 15% decrease in HR on microcirculatory vascular reactivity vs. usual tachycardia management.
Design:
A monocentric, open-label, randomised, superiority clinical trial
Sample size :
44 patients, 22 in each group
Treatments groups:
Continuous intravenous Landiolol injection ( from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in HR on microcirculatory vascular reactivity vs usual tachycardia management
Treatment duration :
24 hours
Assessement:
Landiolol (Rapibloc)'s perfusion will be started at T0 at 0.5 mcg/kg/min and increased by 0.5 mcg/kg/min every 30 minutes in order to achieve a 15% (T1) decrease in HR, within the limit of 10 mcg/kg/min. Then the dosage will be maintained for 2 hours (T2) then the drug will be stopped gradually over 2 hours.
Maximum duration of Landiolol infusion will be 12 hours.
No interim analysis is planned. Analysis will be performed at the end of the study after data review and freezing of database.
- Conditions
- Septic Shock
- Being tested
- Landiolol
- Keywords
- Septic shock, Landiolol, Microcirculatory effects, Heart rate, Hemodynamic effects, Microvascular reactivity
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LandiololDrug
Also called Rapibloc
Intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours) up to a 15% decrease in HR on microcirculatory vascular reactivity.
| Study group | Role | What they receive |
|---|---|---|
| Landiolol injection | Experimental | Intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours) up to a 15% decrease in HR on microcirculatory vascular reactivity. Receives: Drug: Landiolol |
| Usual tachycardia management | No intervention | No treatment, usual tachycardia management. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity
The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in HR on microcirculatory vascular reactivity vs. usual tachycardia management in patients with septic shock.
Measured: 24 hours
Secondary outcomes (5)
Cardiac flow
Measure of the cardiac flow to evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management
Measured: 24 hours
marbling score
Measure of the marbling score to evaluate the effects of Landiolol vs. usual tachycardia management
Measured: 24 hours
skin recoloration time
Measure of skin recoloration time to evaluate the effects of Landiolol vs. usual tachycardia management
Measured: 24 hours
Arterial lactate clearance
Measure of sarterial lactate clearance to evaluate the effects of Landiolol vs. usual tachycardia management
Measured: 24 hours
Measure of Systemic and endothelial inflammation parameters
Evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management on Systemic and endothelial inflammation parameters: Plasma cytokines (Procartaplex) VCAM-1 (vascular endothelial cell adhesion molecule), Soluble Endocan (ELISA)
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start18 Jul 2022
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hafid AIT-OUFELLA, Professor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04931225
- Sponsor's protocol ID
- APHP191047
- Acronym
- MILANOS
- Status last verified
- Jul 2025
- First submitted
- 14 May 2021
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LANdiolol MIcrocirculatory Effects During Septic chOc
- ClinicalTrials.gov ID
- NCT04931225
- Acronym / sponsor ID
- MILANOS / APHP191047
- Conditions
- Septic Shock
- Keywords
- Septic shock, Landiolol, Microcirculatory effects, Heart rate, Hemodynamic effects, Microvascular reactivity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 18 Jul 2022 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 18 Jun 2021 (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.
The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in Heart Rate (HR) on microcirculatory vascular reactivity vs. usual tachycardia management and evaluate the hemodynamic effects of Landiolol vs. usual management in patients with septic shock.
Detailed description
This is a Phase 3, prospective, randomized, open label, evaluation of the efficacy of continuous intravenous Landiolol injection up to a 15% decrease in HR on microcirculatory vascular reactivity vs. usual tachycardia management.
Design:
A monocentric, open-label, randomised, superiority clinical trial
Sample size :
44 patients, 22 in each group
Treatments groups:
Continuous intravenous Landiolol injection ( from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in HR on microcirculatory vascular reactivity vs usual tachycardia management
Treatment duration :
24 hours
Assessement:
Landiolol (Rapibloc)'s perfusion will be started at T0 at 0.5 mcg/kg/min and increased by 0.5 mcg/kg/min every 30 minutes in order to achieve a 15% (T1) decrease in HR, within the limit of 10 mcg/kg/min. Then the dosage will be maintained for 2 hours (T2) then the drug will be stopped gradually over 2 hours.
Maximum duration of Landiolol infusion will be 12 hours.
No interim analysis is planned. Analysis will be performed at the end of the study after data review and freezing of database.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Landiolol injection | Experimental | Drug: LandiololIntravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours) up to a 15% decrease in HR on microcirculatory vascular reactivity. |
| Usual tachycardia management | No intervention | –No treatment, usual tachycardia management. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Sinus tachycardia not compensatory, if the doctor considers that the heart rate acceleration should be treated.
- The study will be carried out in
- reanimated and stabilized septic shock defined as:
- Age >18 years
- Patient (or family member) informed consent signature or emergency consent
Key exclusion criteria (15 listed)
- Asthma
- Patients treated with the following bradycardizing drugs:
- Digitalis
- Bradycardizing calcium channel blockers
- Cordarone
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 |
|---|---|---|
| LandiololAlso: RapiblocIntravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours) up to a 15% decrease in HR on microcirculatory vascular reactivity. | Drug | Landiolol injection |
Primary outcome
Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity
Time frame: 24 hours
The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in HR on microcirculatory vascular reactivity vs. usual tachycardia management in patients with septic shock.
5 secondary outcomes
Cardiac flow
Time frame: 24 hours
marbling score
Time frame: 24 hours
skin recoloration time
Time frame: 24 hours
Arterial lactate clearance
Time frame: 24 hours
Measure of Systemic and endothelial inflammation parameters
Time frame: 24 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Individual participant dataSharing planned: Undecided
Related trials for Septic Shock
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ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
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Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
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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.
Hafid AIT-OUFELLA, Professor principal investigator
Assistance Publique - Hôpitaux de Paris
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 Landiolol in people with Septic Shock, run by Assistance Publique - Hôpitaux de Paris 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 8 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: looking for participants now, as of the sponsor's last update on 1 Aug 2025. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hafid AIT-OUFELLA, Professor (01 49 28 23 15, hafid.aitoufella@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Aug 2025.