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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)

Primary Purpose

Sepsis

Status
Active
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Human albumin
Balanced crystalloid solution
Sponsored by
University of Edinburgh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis focused on measuring Sepsis, Emergency Care, Albumin, Crystalloid, Fluid, Resuscitation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

5% Human Albumin Solution

Intravenous balanced crystalloid

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Recruitment rate
To assess deliverability
30-day mortality
To determine effect size

Secondary Outcome Measures

Data completeness
Feasibility Outcome assessing the percentage of missing data fields in the eCRF
Withdrawal from study
Feasibility Outcomes assessing the number of participants who withdraw from study intervention and/or data collection
Proportion of patients who receive any other fluid apart from intervention or control in first 6 hrs after recruitment
Feasibility Outcomes
Time to start of in-hospital intravenous fluids
Feasibility Outcomes
In-hospital mortality
Secondary Clinical Outcome
90-day mortality
Secondary Clinical Outcome
Volume of randomised fluid delivered in each arm in the first 6hrs and 24hrs
Secondary Clinical Outcome
Length of hospital stay
Secondary Clinical Outcome
Proportion of patients admitted to critical care (HDU/ICU)
Secondary Clinical Outcome
Length of stay in critical care (HDU/ICU)
Secondary Clinical Outcome
Proportion of participants needing intravenous vasopressors
Secondary Clinical Outcome
Proportion of participants needing renal replacement
Secondary Clinical Outcome
Proportion of participants needing invasive ventilation
Secondary Clinical Outcome
Proportion of patients readmitted in first 90 days after discharge
Secondary Clinical Outcome
Proportion of patients developing acute kidney injury
Defined by NICE (https://cks.nice.org.uk/acute-kidney-injury#!scenario)
Proportion of patients developing pulmonary oedema
Safety Radiology diagnosis or requirement for rescue management (new diuretic use)
Proportion of patients developing allergy or anaphylaxis
Requirement for rescue management (antihistamines, adrenaline, intravenous fluids, steroid)
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. 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. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
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.

Full Information

First Posted
August 19, 2020
Last Updated
November 1, 2022
Sponsor
University of Edinburgh
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1. Study Identification

Unique Protocol Identification Number
NCT04540094
Brief Title
Feasibility of 5% Albumin Compared With Balanced Crystalloid, as Intravenous Fluid Resuscitation in Adult Patients With Sepsis, Presenting as an Emergency to Hospital
Acronym
ABC Sepsis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
September 12, 2022 (Actual)
Study Completion Date
April 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Edinburgh

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
Sepsis, Emergency Care, Albumin, Crystalloid, Fluid, Resuscitation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Open label two-arm, multicentre, pragmatic, parallel group randomised trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5% Human Albumin Solution
Arm Type
Experimental
Arm Description
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.
Arm Title
Intravenous balanced crystalloid
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Human albumin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Balanced crystalloid solution
Intervention Description
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.
Primary Outcome Measure Information:
Title
Recruitment rate
Description
To assess deliverability
Time Frame
Approx 1 year
Title
30-day mortality
Description
To determine effect size
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Data completeness
Description
Feasibility Outcome assessing the percentage of missing data fields in the eCRF
Time Frame
180 days
Title
Withdrawal from study
Description
Feasibility Outcomes assessing the number of participants who withdraw from study intervention and/or data collection
Time Frame
Approx 1 year
Title
Proportion of patients who receive any other fluid apart from intervention or control in first 6 hrs after recruitment
Description
Feasibility Outcomes
Time Frame
6 hours
Title
Time to start of in-hospital intravenous fluids
Description
Feasibility Outcomes
Time Frame
From time of Randomisation until fluid first being administered measured up to 6 hours.
Title
In-hospital mortality
Description
Secondary Clinical Outcome
Time Frame
From time of Randomisation until time of hospital discharge or death, whichever is first measured up to 90 days
Title
90-day mortality
Description
Secondary Clinical Outcome
Time Frame
90 days
Title
Volume of randomised fluid delivered in each arm in the first 6hrs and 24hrs
Description
Secondary Clinical Outcome
Time Frame
24 hours
Title
Length of hospital stay
Description
Secondary Clinical Outcome
Time Frame
90 days
Title
Proportion of patients admitted to critical care (HDU/ICU)
Description
Secondary Clinical Outcome
Time Frame
90 days
Title
Length of stay in critical care (HDU/ICU)
Description
Secondary Clinical Outcome
Time Frame
90 days
Title
Proportion of participants needing intravenous vasopressors
Description
Secondary Clinical Outcome
Time Frame
From time of Randomisation until time of hospital discharge, measured up to 90 days.
Title
Proportion of participants needing renal replacement
Description
Secondary Clinical Outcome
Time Frame
From time of Randomisation until time of hospital discharge, measured up to 90 days.
Title
Proportion of participants needing invasive ventilation
Description
Secondary Clinical Outcome
Time Frame
From time of Randomisation until time of hospital discharge, measured up to 90 days.
Title
Proportion of patients readmitted in first 90 days after discharge
Description
Secondary Clinical Outcome
Time Frame
90 days
Title
Proportion of patients developing acute kidney injury
Description
Defined by NICE (https://cks.nice.org.uk/acute-kidney-injury#!scenario)
Time Frame
7 days
Title
Proportion of patients developing pulmonary oedema
Description
Safety Radiology diagnosis or requirement for rescue management (new diuretic use)
Time Frame
7 days
Title
Proportion of patients developing allergy or anaphylaxis
Description
Requirement for rescue management (antihistamines, adrenaline, intravenous fluids, steroid)
Time Frame
7 days
Title
Health Related Quality of life (EQ-5D-5L Questionnaire)
Description
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. 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. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Time Frame
180 days
Title
Secondary care costs
Description
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.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: >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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alasdair Gray
Organizational Affiliation
University of Edinburgh
Official's Role
Study Director
Facility Information:
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
Country
United Kingdom
Facility Name
Addenbrookes Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Derby Teaching Hosptial NHS Foundation Trust
City
Derby
Country
United Kingdom
Facility Name
Royal Infirmary Edinburgh
City
Edinburgh
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Facility Name
Glasgow Royal Infirmary
City
Glasgow
Country
United Kingdom
Facility Name
Queen Elizabeth University Hospital
City
Glasgow
Country
United Kingdom
Facility Name
St Johns
City
Livingston
Country
United Kingdom
Facility Name
St Georges Hospital
City
London
Country
United Kingdom
Facility Name
University College London Hospital
City
London
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Oxford
Country
United Kingdom
Facility Name
Royal Alexandra Hospital
City
Paisley
Country
United Kingdom
Facility Name
Derriford Hospital Plymouth
City
Plymouth
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
Country
United Kingdom
Facility Name
Musgrove Park Hospital
City
Taunton
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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