LANdiolol MIcrocirculatory effects during Septic chOc (MILANOS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

18 Jul 2022 → ongoing

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512757-24-00

EudraCT number

2020-004633-21

ClinicalTrials.gov

NCT04931225

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To study the efficacy of continuous intravenous infusion of Landiolol (0.5 to 10 μg/kg/min for 12 h) up to 15% lower HR on microcirculatory vascular reactivity vs. usual tachycardia management.

Secondary objectives 4

1. To study the hemodynamic effects of Landiolol vs. usual management on : - Cardiac output
2. Clinical perfusion parameters: marbling score, skin recoloration time
3. Arterial lactate clearance
4. Systemic and endothelial inflammation parameters: Plasma cytokines (Procartaplex), VCAM-1, Soluble endocan (ELISA)

Conditions and MedDRA coding

Patients with microcirculatory abnormalities during septic shock

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. -Non-compensatory sinus tachycardia, if the doctor considers that the accelerated heart rate needs to be treated.
2. The study will be carried out in patients in :resuscitated and stabilized septic shock defined by : • Septic shock corresponds to tachycardic patients (HR>100/min) with sepsis (suspected infection + 2 SOFA points) according to the latest international definition (Singer et al. JAMA 2016)) and the need to receive norepinephrine to maintain a mean arterial pressure above 65 mmHg • Patient managed for at least 6 hours, necessary for diagnostic management and hemodynamic optimization according to international standards (Dellinger et al. Crit Care Med 2013) and for less than 24 hours to limit confounding factors related to prolonged resuscitation (sedation) and empowerment of organ failure in general and vascular failure in particular. Hemodynamic stabilization will be defined as the absence of an increase in norepinephrine dosages in the previous two hours to limit the risk of arterial hypotension induced by Landiolol infusion.
3. Signature of patient's (or family member's) informed consent or emergency consent.
4. -Age ≥ 18 years
5. Social Security affiliation

Exclusion criteria 17

1. -Asthma
2. Patients treated with the following bradycardia drugs : Digitalis, Bradycardia-inducing, calcium channel blockers, Cordarone, Other beta-blockers
3. Hypersensitivity to Landiolol or any of its excipients (Mannitol E421, sodium hydroxide)
4. Sinus disease
5. Cardiogenic shock
6. Decompensated heart failure when considered unrelated to arrhythmia
7. Pregnant or breast-feeding women
8. Participation in other interventional research involving the human person or being within the exclusion period following previous research involving the human person, if applicable
9. Patients under guardianship or trusteeship
10. Moribund patient
11. Estimated life expectancy less than 1 month
12. Patients with severe atrioventricular conduction disorders (without pacemaker)
13. -Second- and third-degree atrioventricular blocks
14. Pulmonary hypertension
15. Untreated pheochromocytoma
16. Moribund patients with very severe acidosis
17. Left ventricular ejection fraction <30%.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Variation (%) in microcirculatory vascular reactivity (T2-T0/T0x100).

Secondary endpoints 4

1. Variation (%) in cardiac output (echocardiography)
2. Variation (%) in clinical perfusion parameters between T0 and T2: mottling score, skin recoloration time, hourly diuresis
3. Variation (%) in arterial lactate clearance between T0 and T2
4. Variation (%) in systemic and endothelial inflammation parameters between T0 and T2 : Plasma cytokines (Procartaplex), VCAM-1 soluble, Soluble Endocan

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Hafid AIT-OUFELLA

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Hafid AIT-OUFELLA

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications