STRESS-L: STudy into the REversal of Septic Shock with Landiolol (Beta Blockade)

Phase 1

Conditions: Tachycardia in Septic Shock
MedDRA version: 20.0Level: PTClassification code 10040070Term: Septic shockSystem Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.0Level: PTClassification code 10043071Term: TachycardiaSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2017-001785-14-GB

Lead Sponsor: niversity Hospitals Birmingham NHS Foundation Trust

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 340

Inclusion Criteria

• Male or female aged 18 years or above
• Being treated on an ICU
• Septic shock according to internationally accepted definitions*
• Heart rate =95 bpm (24 hours after start of vasopressor therapy)
• Receiving vasopressor support with noradrenaline to maintain a target blood pressure for =24 hours
• Are being treated with noradrenaline at a rate = 0.1mcg/kg/min

*Sepsis -3 definitions:
o confirmed or suspected infection requiring antibiotic therapy
o new organ dysfunction, as evidenced by an increase in SOFA score =2
o a blood lactate >2 mmol/l at any point during shock resuscitation
o vasopressor therapy to maintain mean arterial pressure (MAP) =65 mmHg

In particular the presence of a blood lactate > 2 mmol/l is only necessary for the diagnosis of septic shock and is NOT necessary for randomisation 24 hours later.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

The participant may not enter the trial if any of the following apply:
•Noradrenaline infusion <0.1mcg/kg/min
•>48 hours after start of vasopressor therapy
•Having pre-existing severe cardiac dysfunction (NYHA grade 4 or more)
•Having pre-existing severe pulmonary hypertension (mean PA pressures > 55mmHg)
•Acute severe bronchospasm (due to asthma or COPD)
•Untreated second or third degree heart block
•Untreated pheochromocytoma
•Prinzmetal's angina
•A past history of ischaemic stroke or transient ischaemic attack (TIA) or untreated severe carotid stenosis.
•Advanced liver disease
•Having been treated with any beta-blocker drug in the seventy two hours prior to screening.
•Known sensitivity to beta-blockers
•Patient / legal representative unwilling to provide written informed consent
•Known to be pregnant
•Terminal illness other than septic shock with a life expectancy < 28 days
•Participants who have participated in another research trial involving an investigational medicinal product in the past 30 days.
•Patients in whom the clinical team feel are about to finish their noradrenaline therapy.