Feasibility of 5% Albumin Compared With Balanced Crystalloid, as Intravenous Fluid Resuscitation in Adult Patients With Sepsis, Presenting as an Emergency to Hospital
- Registration Number
- NCT04540094
- Lead Sponsor
- University of Edinburgh
- Brief Summary
The aim of this research study is to compare two different fluids (Human Albumin Solution (HAS) and Balanced Crystalloid that are given via a drip to patients with severe infection (sepsis). The investigators plan to see which fluid is better, and to see if they have a role in improving a patient's recovery time, reducing complications and the length of time they stay in hospital. This study plans to find out if there is evidence that one fluid is better overall to determine the need for a subsequent definitive trial.
- Detailed Description
This trial will be an open label two-arm, multicentre, pragmatic, parallel group randomised trial of adult patients with community acquired sepsis recruited from the Emergency Department and Medical and Surgical Assessment Units across \~10 UK NHS Hospitals. The treatment phase will be the first 6 hours following randomisation. 30-day and 90-day follow up will be conducted using routine data only. The exception to this will be the first 50 patients enrolled in the study, Health Related Quality of Life (HRQoL) will be measured using the EQ-5D-5L at baseline, 7 days and at 180 days. At baseline, the participant or their relative will be asked to recall the quality of life 4 weeks prior to the index hospital admission. Questionnaires will be administered by direct patient completion or, postal or email survey with telephone follow up for non-responders after two mailings two weeks apart.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
Adult patients (18 years or older) who present to UK NHS hospitals with community acquired sepsis meeting all of the 4 criteria:
- Clinically suspected or proven infection resulting in principal reason for acute illness;
- NEWS score ≥5 (or NEWS2 if adopted in recruitment site);
- Hospital presentation within last 12hrs; and
- Clinician decision has been made that immediate (within 1 hour) intravenous fluid resuscitation is needed.
- >1 litre of intravenous crystalloid fluid or any intravenous HAS administered prior to eligibility assessment;
- Requirement for immediate surgery (within one hour of eligibility assessment);
- Chronic renal replacement therapy;
- Known allergy/adverse reaction to HAS;
- Balanced crystalloid or HAS not available;
- Known adverse reaction to blood products;
- Palliation/end of life care (explicit decision by patient/family/carers in conjunction with clinical team that any active treatment beyond symptomatic relief is not appropriate);
- Religious beliefs precluding HAS administration;
- Previous recruitment in the trial;
- Known recent severe traumatic brain injury (within 3 months);
- Patients with permanent incapacity;
- Known recruitment in another CTIMP studies within the last 30 days where co-enrolment has not been agreed.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 5% Human Albumin Solution Human albumin Participants allocated to the treatment arm will receive intravenous 5% Human Albumin Solution (HAS) administered as the sole intravenous fluid during the initial 6-hour resuscitation period. The clinician can deliver up to 10ml/kg in the first 3 hours using 250ml boluses of HAS based on clinical judgement, using clinical assessment supplemented by technology if that is their usual practice. This will be followed by repeat clinical assessment after each bolus (including vital signs; lactate testing). After 3 hours further HAS boluses up to 6 hours post-randomisation will be at clinical discretion and will be documented in the CRF. Patients in the albumin arm should not receive balanced crystalloid as a resuscitation fluid in the first 6 hours. Intravenous balanced crystalloid Balanced crystalloid solution Participant allocated to the usual care arm will receive intravenous balanced crystalloid administered as the sole intravenous fluid during the initial 6 hour resuscitation period. The clinician can deliver up to 30ml/kg in the first 3 hours using 250ml boluses of balanced crystalloid based on clinical judgement, using clinical assessment supplemented by technology if that is their usual practice. This will be followed by repeat clinical assessment after each bolus (including vital signs; lactate testing). Thereafter, further crystalloid boluses up to 6 hours will be at the discretion of the clinical team and will be documented in the CRF. Patients in the balanced crystalloid arm should not receive albumin as a resuscitation fluid in the first 6 hours.
- Primary Outcome Measures
Name Time Method Recruitment Rate Approx 1 year We measured the recruitment rate to assess deliverability. We aimed to recruit 300 participants in approximately 1 year in a 1:1 ratio into each treatment arm.
30-day Mortality 30 days Assessment of how many participants in each arm died after 30 days to determine the effect size between the treatment groups.
- Secondary Outcome Measures
Name Time Method Data Completeness of Primary Outcome 180 days Feasibility Outcome assessing the number of participants who provided data for clinical primary outcome (30 day mortality)
Withdrawal From Study Approx 1 year Feasibility Outcomes assessing the number of participants who withdraw from study intervention and/or data collection
Number of Patients Who Receive Any Other Fluid Apart From Intervention or Control in First 6 Hrs After Recruitment 6 hours Feasibility Outcome- number of patients who receive any other fluid apart from intervention or control in first 6 hrs after recruitment
Time to Start of In-hospital Intravenous Fluids From time of Randomisation until fluid first being administered measured up to 6 hours. Feasibility Outcome- Time to start of in-hospital intravenous fluids
In-hospital Mortality From time of Randomisation until time of hospital discharge or death, whichever is first measured up to 90 days Secondary Clinical Outcome
90-day Mortality 90 days Secondary Clinical Outcome
Volume of Randomised Fluid Delivered in Each Arm in the First 6hrs 6 hours Secondary Clinical Outcome- Volume of randomised fluid delivered in each arm in the first 6hrs
Length of Hospital Stay 90 days Secondary Clinical Outcome
Proportion of Patients Admitted to Critical Care (HDU/ICU) 90 days Secondary Clinical Outcome- Proportion of patients admitted to critical care (HDU/ICU)
Length of Stay in Critical Care (HDU/ICU) 90 days Secondary Clinical Outcome- Length of stay in critical care (HDU/ICU)
Number of Participants Needing Intravenous Vasopressors From time of Randomisation until time of hospital discharge, measured up to 90 days. Secondary Clinical Outcome-number of participants needing intravenous vasopressors
Number of Participants Needing Renal Replacement From time of Randomisation until time of hospital discharge, measured up to 90 days. Secondary Clinical Outcome- Number of participants needing renal replacement
Number of Participants Needing Invasive Ventilation From time of Randomisation until time of hospital discharge, measured up to 90 days. Secondary Clinical Outcome- Number of participants needing invasive ventilation
Number of Patients Readmitted in First 90 Days After Discharge 90 days Secondary Clinical Outcome- Number of patients readmitted in first 90 days after discharge
Number of Patients Developing Acute Kidney Injury (AKI) 7 days AKI Defined using National Institute for Health and Care Excellence (NICE) criteria:
A diagnosis of AKI may be made if there is one of the following:
A rise in serum creatinine of 26 micromol/L or greater within 48 hours. A 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days.
A fall in urine output to less than 0.5 mL/kg/hour for more than 6 hours.Number of Patients Developing Pulmonary Oedema 7 days Safety Radiology diagnosis or requirement for rescue management (new diuretic use)
Number of Patients Developing Allergy or Anaphylaxis 7 days Requirement for rescue management (antihistamines, adrenaline, intravenous fluids, steroid)
Health Related Quality of Life (EQ-5D-5L Questionnaire) 180 Days Health Economic Outcomes are measured using the the 5-level EQ-5D version (EQ-5D-5L). The EQ-5D-5L descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. A high score indicates a worse outcome. The patient is asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions. The digits for the five dimensions can be combined into a 5-digit number (profile) that describes the patient's health state. The EQ-5D profile can be converted to a single number between 0-1 called the EQ-5D value. These EQ-5D values to lie on between 0-1 to indicate health where 0 represents the minimum score (dead) and 1 is full health. Values less than 0 are possible for health states considered worse than dead.
Secondary Care Costs 30 days Costs will be estimated by assigning national standard unit costs to inpatient stays (critical care and general ward level), readmissions and additional high costs activities observed in the study. Baseline (pre-admission) HQoL will be estimated using age/sex matched population reference data.
Volume of Randomised Fluid Delivered in Each Arm in the First 24hrs 24 hours Secondary Clinical Outcome-Volume of randomised fluid delivered in each arm in the first 24hrs
Trial Locations
- Locations (15)
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
St Georges Hospital
🇬🇧London, United Kingdom
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Royal Infirmary Edinburgh
🇬🇧Edinburgh, United Kingdom
Derby Teaching Hosptial NHS Foundation Trust
🇬🇧Derby, United Kingdom
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
St Johns
🇬🇧Livingston, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Royal Alexandra Hospital
🇬🇧Paisley, United Kingdom
Derriford Hospital Plymouth
🇬🇧Plymouth, United Kingdom