A large clinical trial across 60 NHS hospitals will test whether giving the drug norepinephrine early through a peripheral vein can save more lives from septic shock than the current standard of giving fluids first. Sepsis kills tens of thousands of people in the UK each year. When blood pressure drops dangerously low, doctors currently rush to infuse large volumes of intravenous fluids. But fluids can cause fluid overload, worsening lung and kidney function. An alternative is to start a vasopressor drug like norepinephrine earlier, which raises blood pressure directly. No large UK trial has yet determined which approach is better for survival. If the trial shows that early peripheral norepinephrine reduces deaths, it could change the immediate treatment protocol for septic shock in emergency departments and acute medical units across the NHS. This would affect a common, life-threatening condition that clinicians manage daily. The trial also includes a health economic analysis to assess whether the approach saves the NHS money over the long term, and an embedded qualitative study to understand how easily the new protocol could be adopted by busy clinical staff.
View original technical description
Population: Adults presenting to an ED, AMU or SAU with signs or symptoms of community acquired sepsis and a SBP 2mmol/l Intervention: Intravenous Norepinephrine infusion administered via a peripheral intravenous cannula in the first 48 hrs after randomisation to a target MAP>65mmHg. Control group treatment: Intravenous crystalloid administered as 250-1000ml boluses up to 30ml/kg in the first 3 hours after randomisation, and thereafter according to national guidelines for remaining 45 hours to a target MAP>65mmHg. Outcome: 30 day mortality Design: open label two-arm, multicentre, pragmatic, parallel group definitive randomised trial of adult patients with community acquired septic shock recruited from the ED, AMU or SAU. There will be an internal pilot with progression from pilot to main study assessed on (a) recruitment feasibility and (b) protocol adherence. Setting: 60 ED and AMU within NHS hospitals with patient case mix typical of UK acute care, with a proven track record of successful participation in NIHR Portfolio national clinical trials. Population: Adult patients who present to UK NHS hospitals with community acquired septic shock Inclusion criteria A. Adults (18 years and older); B. Suspected or confirmed infection causing acute illness; C. SBP 2; D. Hospital presentation within last 6hrs. Exclusion criteria A. >1000ml of iv fluid prior to screening; B. Requirement for Immediate surgery; C. Established chronic renal replacement therapy; D. Confirmed pregnancy/lactation; E. Known allergy/adverse reaction to NE; F. No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial G. Previous recruitment in the trial Secondary outcomes during first 48 hours: volume of iv fluid delivered in each arm in the first 6,12,24,48hrs; rate of lactate clearance at 3,6hrs; SOFA score at 0, 24,48hrs; total dose of NE delivered in first 6,12,24,48hrs. Vasopressor ucontrol arm. Protocol Adherence: Proportion of patients who have PVI discontinued for non-clinical reasons after recruitment to intervention arm; Safety: proportion of patients developing vasopressor extravasation, worsening acute kidney injury or pulmonary oedema Process evaluation: embedded qualitative research to: (a) establish the extent to which the intervention is implemented as intended; (b) ascertain how feasible and acceptable the intervention is to clinical staff; and (c) identify any facilitators and barriers to recruitment. This will consist of a rapid ethnographic assessment. Longer term follow up: 90 day mortality, length of hospital stay for index admission; readmission in first 30 days after discharge; critical care stay and interventions Health Economic evaluation: This will be conducted from the perspective of the NHS and PSS in line with NICE guidance. Data on healthcare resource use will include inpatient and community care health services. Unit costs will be obtained from standard sources. HRQoL will be assessed at baseline, 30 days and 6 months using EQ5D-5L. Patient-level costs and quality adjusted life years (QALYs) will be estimated. Within trial and a model-based analyses will be undertaken based on six-month and lifetime horizon, respectively. All appropriate deterministic and probabilistic sensitivity analyses will be carried out
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know