Feasibility of 5% Albumin Compared With Balanced Crystalloid, as Intravenous Fluid Resuscitation in Adult Patients With Sepsis, Presenting as an Emergency to Hospital (ABC Sepsis)

Feasibility of 5% Albumin Compared With Balanced Crystalloid, as Intravenous Fluid Resuscitation in Adult Patients With Sepsis, Presenting as an Emergency to Hospital: ABC Sepsis Trial

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Drug: Human albumin; Drug: Balanced crystalloid solution

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom
    • Aberdeen Royal Infirmary
  • Cambridge, United Kingdom
    • Addenbrookes Hospital
  • Derby, United Kingdom
    • Derby Teaching Hosptial NHS Foundation Trust
  • Edinburgh, United Kingdom
    • Royal Infirmary Edinburgh
  • Exeter, United Kingdom
    • Royal Devon and Exeter Hospital
  • Glasgow, United Kingdom
    • Glasgow Royal Infirmary
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • Livingston, United Kingdom
    • St Johns
  • London, United Kingdom
    • University College London Hospital
  • London, United Kingdom
    • St Georges Hospital
  • Oxford, United Kingdom
    • John Radcliffe Hospital
  • Paisley, United Kingdom
    • Royal Alexandra Hospital
  • Plymouth, United Kingdom
    • Derriford Hospital Plymouth
  • Salford, United Kingdom
    • Salford Royal NHS Foundation Trust
  • Taunton, United Kingdom
    • Musgrove Park Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Adult patients (18 years or older) who present to UK NHS hospitals with community acquired sepsis meeting all of the 4 criteria:

1. Clinically suspected or proven infection resulting in principal reason for acute illness;
2. NEWS score ≥5 (or NEWS2 if adopted in recruitment site);
3. Hospital presentation within last 12hrs; and
4. Clinician decision has been made that immediate (within 1 hour) intravenous fluid resuscitation is needed.

Exclusion Criteria:

1. >1 litre of intravenous crystalloid fluid or any intravenous HAS administered prior to eligibility assessment;
2. Requirement for immediate surgery (within one hour of eligibility assessment);
3. Chronic renal replacement therapy;
4. Known allergy/adverse reaction to HAS;
5. Balanced crystalloid or HAS not available;
6. Known adverse reaction to blood products;
7. 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);
8. Religious beliefs precluding HAS administration;
9. Previous recruitment in the trial;
10. Known recent severe traumatic brain injury (within 3 months);
11. Patients with permanent incapacity;
12. Known recruitment in another CTIMP studies within the last 30 days where co-enrolment has not been agreed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5% Human Albumin Solution; 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.	Drug: Human albumin; Any preparation of 5% Human Albumin Solution which has marketing authorisation in the UK to be used for this indication and is stocked by local hospital pharmacies at the participating sites, may be prescribed in this study
Active Comparator: Intravenous balanced crystalloid; 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.	Drug: Balanced crystalloid solution; Any preparation of intravenous "balanced" crystalloid which has marketing authorisation in the UK to be used for this indication and is stocked by local hospital pharmacies at the participating sites, may be prescribed in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	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.	Approx 1 year
30-day Mortality	Assessment of how many participants in each arm died after 30 days to determine the effect size between the treatment groups.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Data Completeness of Primary Outcome	Feasibility Outcome assessing the number of participants who provided data for clinical primary outcome (30 day mortality)	180 days
Withdrawal From Study	Feasibility Outcomes assessing the number of participants who withdraw from study intervention and/or data collection	Approx 1 year
Number of Patients Who Receive Any Other Fluid Apart From Intervention or Control in First 6 Hrs After Recruitment	Feasibility Outcome- number of patients who receive any other fluid apart from intervention or control in first 6 hrs after recruitment	6 hours
Time to Start of In-hospital Intravenous Fluids	Feasibility Outcome- Time to start of in-hospital intravenous fluids	From time of Randomisation until fluid first being administered measured up to 6 hours.
In-hospital Mortality	Secondary Clinical Outcome	From time of Randomisation until time of hospital discharge or death, whichever is first measured up to 90 days
90-day Mortality	Secondary Clinical Outcome	90 days
Volume of Randomised Fluid Delivered in Each Arm in the First 6hrs	Secondary Clinical Outcome- Volume of randomised fluid delivered in each arm in the first 6hrs	6 hours
Length of Hospital Stay	Secondary Clinical Outcome	90 days
Proportion of Patients Admitted to Critical Care (HDU/ICU)	Secondary Clinical Outcome- Proportion of patients admitted to critical care (HDU/ICU)	90 days
Length of Stay in Critical Care (HDU/ICU)	Secondary Clinical Outcome- Length of stay in critical care (HDU/ICU)	90 days
Number of Participants Needing Intravenous Vasopressors	Secondary Clinical Outcome-number of participants needing intravenous vasopressors	From time of Randomisation until time of hospital discharge, measured up to 90 days.
Number of Participants Needing Renal Replacement	Secondary Clinical Outcome- Number of participants needing renal replacement	From time of Randomisation until time of hospital discharge, measured up to 90 days.
Number of Participants Needing Invasive Ventilation	Secondary Clinical Outcome- Number of participants needing invasive ventilation	From time of Randomisation until time of hospital discharge, measured up to 90 days.
Number of Patients Readmitted in First 90 Days After Discharge	Secondary Clinical Outcome- Number of patients readmitted in first 90 days after discharge	90 days
Number of Patients Developing Acute Kidney Injury (AKI)	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.	7 days
Number of Patients Developing Pulmonary Oedema	Safety Radiology diagnosis or requirement for rescue management (new diuretic use)	7 days
Number of Patients Developing Allergy or Anaphylaxis	Requirement for rescue management (antihistamines, adrenaline, intravenous fluids, steroid)	7 days
Health Related Quality of Life (EQ-5D-5L Questionnaire)	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.	baseline
Secondary Care Costs	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.	30 days
Volume of Randomised Fluid Delivered in Each Arm in the First 24hrs	Secondary Clinical Outcome-Volume of randomised fluid delivered in each arm in the first 24hrs	24 hours
Health Related Quality of Life (EQ-5D-5L Questionnaire)	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.	7 Days
Health Related Quality of Life (EQ-5D-5L Questionnaire)	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.	180 Days

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Investigators: Study Director: Alasdair Gray, University of Edinburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Sepsis; Crystalloid; Resuscitation; Fluid; Albumin; Emergency Care
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Toxemia; Emergencies
• Other Study ID Numbers: AC20043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The intention is to share anonymised data with external collaborators and scientists one year after the primary publication has been published (anticipated Jun 2022).
• IPD Sharing Time Frame: From 2023
• IPD Sharing Access Criteria: Requests can be made by email to the Chief Investigator from 2023.
• IPD Sharing Supporting Information Type: ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No