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RECRUITINGPhase 3INTERVENTIONAL

Early Vasopressors in Sepsis

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

Sepsis is a life-threatening reaction to an infection. It happens when the immune system overreacts to an infection and starts to damage the body's tissues and organs. The aim of this research study is to compare the two different ways to treat sepsis, in the early phase of treatment immediately after the participants arrive in hospital. The standard approach is to give a salt solution fluid through a drip in the participants arm to start with, then adding in a medication that increases the blood flow to the participants vital organs (a vasopressor mediation called norepinephrine) if required. The alternative approach is to start the vasopressor medication immediately, and then add in extra salt solution fluid via a drip if required. Vasopressors work by increasing the blood pressure which allows a better blood flow to the internal organs. The investigators plan to see which approach is better and to see if they have a role in improving a patient's recovery time, reducing complications, the length of time they stay in hospital and longer term poor health. Based on research that has already been done, the investigators believe treating patients with vasopressors when they arrive in the Emergency Department, may have potential advantages over the standard fluids used today. However, the evidence is not clear and that is why this research is being done.

Who May Be Eligible (Plain English)

Who May Qualify: - Age \>18 years - Clinically suspected or proven infection resulting in principal reason for acute illness - SBP \< 90 mmHg or MAP of \< 65 mmHg (within an hour of eligibility assessment) - Measured serum lactate of \> 2 mmol/L. The serum lactate should be measured 2 hours prior to determination of eligibility, where possible. Longer timeframes may be used and justified within the medical notes if, in the opinion of the investigator, the clinical status of the patient has not significantly improved in the time interval between lactate measurement and eligibility assessment. Lactate measurements more than 4 hours prior to eligibility assessment should not normally be used. - Hospital presentation within last 12 hours Who Should NOT Join This Trial: - \>1500ml of intravenous fluid prior to screening - Clinically judged to require immediate surgery (within one hour of eligibility assessment) - Immediate (\< 1 hour) requirement for central venous access - Chronic renal replacement therapy - Known allergy/adverse reaction to norepinephrine - Palliation / end of life care (explicit decision by patient/family/carer in conjunction with clinical team that active treatment beyond symptomatic relief is not appropriate) - Previous recruitment in the trial - Patients with permanent incapacity - Pregnancy. All women of childbearing potential (WoCBP) must have a negative urine or serum pregnancy test result completed as part of screening requirements. WoCBP are defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. - Other primary causes of shock (e.g. suspected cardiogenic shock, haemorrhagic shock, etc) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * Age \>18 years * Clinically suspected or proven infection resulting in principal reason for acute illness * SBP \< 90 mmHg or MAP of \< 65 mmHg (within an hour of eligibility assessment) * Measured serum lactate of \> 2 mmol/L. The serum lactate should be measured 2 hours prior to determination of eligibility, where possible. Longer timeframes may be used and justified within the medical notes if, in the opinion of the investigator, the clinical status of the patient has not significantly improved in the time interval between lactate measurement and eligibility assessment. Lactate measurements more than 4 hours prior to eligibility assessment should not normally be used. * Hospital presentation within last 12 hours Exclusion Criteria: * \>1500ml of intravenous fluid prior to screening * Clinically judged to require immediate surgery (within one hour of eligibility assessment) * Immediate (\< 1 hour) requirement for central venous access * Chronic renal replacement therapy * Known allergy/adverse reaction to norepinephrine * Palliation / end of life care (explicit decision by patient/family/carer in conjunction with clinical team that active treatment beyond symptomatic relief is not appropriate) * Previous recruitment in the trial * Patients with permanent incapacity * Pregnancy. All women of childbearing potential (WoCBP) must have a negative urine or serum pregnancy test result completed as part of screening requirements. WoCBP are defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. * Other primary causes of shock (e.g. suspected cardiogenic shock, haemorrhagic shock, etc) * History or evidence of any other medical, neurological or psychological condition that would expose the subject to an undue risk of a significant Adverse Effect as determined by the clinical judgement of the investigator * Participation in other clinical trials of investigational medicinal products

Treatments Being Tested

DRUG

Norepinephrine

Norepinepherine should be prepared and delivered at a concentration of 16 micrograms/ml

OTHER

Balanced Crystalloid

IV fluids administered as per standard care

Locations (20)

Aintree University Hospital
Aintree, United Kingdom
Royal Blackburn Hospital
Blackburn, United Kingdom
Fairfield General Hospital
Bury, United Kingdom
Addenbrookes Hospital, Cambridge
Cambridge, United Kingdom
Royal Derby Hospital
Derby, United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom
Victoria Hospital
Fife Keith, United Kingdom
Glasgow Royal Infirmary
Glasgow, United Kingdom
Queen Elizabeth University Hospital
Glasgow, United Kingdom
Hull Royal Infirmary
Hull, United Kingdom
Kettering General
Kettering, United Kingdom
University Hospital Crosshouse
Kilmarnock, United Kingdom
University Hospital Monklands
Lanark, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom
Newham University Hospital
London, United Kingdom
Royal London Hospital
London, United Kingdom
St George's
London, United Kingdom
University Hospital Lewisham
London, United Kingdom
John Radcliffe Hospital
Oxford, United Kingdom