Comparison of Landiolol versus standard of care for prevention of mortality in patients hospitalized for a septic shock with hypercontractlity: an open label prospective randomized study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Amiens Picardie

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]

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518251-31-00

EudraCT number

2020-002671-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

is to demonstrate that the reduction of heart rate using the landiolol may improve the mortality of septic shock patients with tachycardia and hypercontractility in comparison to control group at day 28

Secondary objectives 1

1. Secondary objectives are to demonstrate that the reduction of heart rate using the landiolol in comparison to standard of care may: - Reduce tachycardia - Reduce hypercontractility - Reduce shock duration - Reduce the length of stay - Reduce the multi organ failure - Reduce the incidence of atrial fibrillation

Conditions and MedDRA coding

patients hospitalized for a septic shock with hypercontractlity

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years old
2. Patient with a septic shock (according to the SEPSIS3 definition: sepsis with persisting hypotension (MAP<65mmHg or SAP <90mmHg) requiring vasopressors to maintain MAP>65mmHg with at least one lactate dosage >2 mmol/L during the current shock episode.
3. patient who received between 10 and 30ml/kg of fluid and absence of fluid responsiveness
4. Left ventricular ejection fraction > 60 % (visual or Simpson method using echocardiography)
5. Tachycardia >95 bpm with a MAP 65mmHg for more than 1 hour
6. Patient either in spontaneous ventilation or intubated and ventilated

Exclusion criteria 18

1. Patients with inclusion criteria already present for more than 36 hours
2. Patient treated with Dobutamine, adrenaline or isoprenaline
3. Patient currently treated with beta blockers (previous home betablocker treatment is not an exclusion criteria)
4. Patients with any form of cardiac pacing
5. Sick sinus syndrome
6. Severe atrioventricular (AV) nodal conductance disorders (without pacemaker): 2nd or 3rd degree AV block
7. Known pulmonary hypertension
8. Moribund
9. in- or out-of-hospital cardiac arrest without signs of early recovery
10. Non-treated phaeochromocytoma
11. Acute asthmatic attack
12. Hypersensitivity to the active substance or to any of the excipients
13. Severe bradycardia (less than 50 beats per minute)
14. Cardiogenic shock
15. Severe hypotension uncontrolled
16. Decompensated heart failure when considered not related to the errhythmia
17. Severe, uncorrectable metabolic acidosis
18. Presence of significant bleeding, or spontaneously ventilated patient in respiratory distress requiring immediate intubation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. mortality at day 28

Secondary endpoints 9

1. - Number of patients that achieved a reduction of heart rate equal or higher to 20% of the initial HR with landiolol
2. - Number of days receiving catecholamines
3. - Number of days receiving mechanical ventilation
4. - Length of stay in ICU and hospital
5. - SOFA score at inclusion and day 1, 2, 3, 7, 14 and 28 following the inclusion
6. - Number of patients developing atrial fibrillation of flutter during the first three days
7. - Hospital mortality
8. - Number of episodes of bradycardia (<50 bpm) or LVEF < 45% or MAP <65mmHg requiring an increase of Norepinephrine > 40% during the entire period of treatment with the landiolol
9. - Unexpected cardiac arrest

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Amiens Picardie

Sponsor organisation

Centre Hospitalier Universitaire Amiens Picardie

Address

1 Rond Point Du Pr Christian Cabrol

City

Amiens Cedex 1

Postcode

80054

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Amiens Picardie

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire Amiens Picardie

Contact name

Projet manager

Locations

1 EU/EEA country · 39 investigational sites

By country

Investigational sites

Results and documents

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

Documents 16 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