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

NCT04540094 | Completed Phase 3 Results DMC

• 1 other identifier: AC20043
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 15

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.

Conditions

Sepsis

Keywords

Sepsis; Emergency Care; Albumin; Crystalloid; Fluid; Resuscitation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (22)

• Data Completeness of Primary Outcome

  180 days

• Withdrawal From Study

  Approx 1 year

• 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

  From time of Randomisation until fluid first being administered measured up to 6 hours.

• In-hospital Mortality

  From time of Randomisation until time of hospital discharge or death, whichever is first measured up to 90 days

Study Arms (2)

5% Human Albumin Solution

EXPERIMENTAL

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

Intravenous balanced crystalloid

ACTIVE COMPARATOR

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

Interventions

Human albumin DRUG

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

5% Human Albumin Solution

Balanced crystalloid solution DRUG

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.

Intravenous balanced crystalloid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \>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.

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (15)

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

Derby Teaching Hosptial NHS Foundation Trust

Derby, United Kingdom

Location

Royal Infirmary Edinburgh

Edinburgh, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

St Johns

Livingston, United Kingdom

Location

St Georges Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

John Radcliffe Hospital

Oxford, United Kingdom

Location

Royal Alexandra Hospital

Paisley, United Kingdom

Location

Derriford Hospital Plymouth

Plymouth, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

Musgrove Park Hospital

Taunton, United Kingdom

Location

Related Publications (1)

• Gray AJ, Oatey K, Grahamslaw J, Irvine S, Cafferkey J, Kennel T, Norrie J, Walsh T, Lone N, Horner D, Appelboam A, Hall P, Skipworth RJE, Bell D, Rooney K, Shankar-Hari M, Corfield AR; Albumin, Balanced, and Crystalloid-Sepsis (ABC-Sepsis) Investigators. Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial- The ABC-Sepsis Trial. Crit Care Med. 2024 Oct 1;52(10):1520-1532. doi: 10.1097/CCM.0000000000006348. Epub 2024 Jun 24.

  PMID: 38912884 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Limitations and Caveats

Full Health Economic Analysis was not possible to determine the difference in secondary care costs. It was determined that any comparative analysis of costs would be dominated by mortality difference between arms, with the inevitable lower costs and quality-adjusted life years (QALYs) associated with the higher mortality group, so full analysis of this data was not completed as it would not produce meaningful outcomes. All analyses outlined in the Statistical Analysis Plan were completed.

Results Point of Contact

• Title: Prof Alasdair Gray
• Organization: University of Edinburgh

alasdair.gray@ed.ac.uk

0131 242 1340

Study Officials

• Alasdair Gray

  University of Edinburgh

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label two-arm, multicentre, pragmatic, parallel group randomised trial

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: September 7, 2020
• Study Start: June 1, 2021
• Primary Completion: September 12, 2022
• Study Completion: April 30, 2023
• Last Updated: October 4, 2024
• Results First Posted: October 4, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR, ANALYTIC CODE
• Time Frame: From 2023
• Access Criteria: Requests can be made by email to the Chief Investigator from 2023.

Locations

GB (15)