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)

• ClinicalTrials.gov Identifier: NCT04540094
• Recruitment Status: Not yet recruiting
• First Posted: September 7, 2020
• Last Update Posted: April 28, 2021
• Sponsor: University of Edinburgh
• Information provided by (Responsible Party): University of Edinburgh

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.

Condition or disease	Intervention/treatment	Phase
Sepsis	Drug: Human albumin; Drug: Balanced crystalloid solution	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open label two-arm, multicentre, pragmatic, parallel group randomised trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: June 1, 2021
• Estimated Primary Completion Date: June 28, 2022
• Estimated Study Completion Date: September 30, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Recruitment rate [ Time Frame: Approx 1 year ]
   To assess deliverability
2. 30-day mortality [ Time Frame: 30 days ]
   To determine effect size

Secondary Outcome Measures :

1. Data completeness [ Time Frame: 180 days ]
   Feasibility Outcome assessing the percentage of missing data fields in the eCRF
2. Withdrawal from study [ Time Frame: Approx 1 year ]
   Feasibility Outcomes assessing the number of participants who withdraw from study intervention and/or data collection
3. Proportion of patients who receive any other fluid apart from intervention or control in first 6 hrs after recruitment [ Time Frame: 6 hours ]
   Feasibility Outcomes
4. Time to start of in-hospital intravenous fluids [ Time Frame: From time of Randomisation until fluid first being administered measured up to 6 hours. ]
   Feasibility Outcomes
5. In-hospital mortality [ Time Frame: From time of Randomisation until time of hospital discharge or death, whichever is first measured up to 90 days ]
   Secondary Clinical Outcome
6. 90-day mortality [ Time Frame: 90 days ]
   Secondary Clinical Outcome
7. Volume of randomised fluid delivered in each arm in the first 6hrs and 24hrs [ Time Frame: 24 hours ]
   Secondary Clinical Outcome
8. Length of hospital stay [ Time Frame: 90 days ]
   Secondary Clinical Outcome
9. Proportion of patients admitted to critical care (HDU/ICU) [ Time Frame: 90 days ]
   Secondary Clinical Outcome
10. Length of stay in critical care (HDU/ICU) [ Time Frame: 90 days ]
    Secondary Clinical Outcome
11. Proportion of participants needing intravenous vasopressors [ Time Frame: From time of Randomisation until time of hospital discharge, measured up to 90 days. ]
    Secondary Clinical Outcome
12. Proportion of participants needing renal replacement [ Time Frame: From time of Randomisation until time of hospital discharge, measured up to 90 days. ]
    Secondary Clinical Outcome
13. Proportion of participants needing invasive ventilation [ Time Frame: From time of Randomisation until time of hospital discharge, measured up to 90 days. ]
    Secondary Clinical Outcome
14. Proportion of patients readmitted in first 90 days after discharge [ Time Frame: 90 days ]
    Secondary Clinical Outcome
15. Proportion of patients developing acute kidney injury [ Time Frame: 7 days ]
    Defined by NICE (https://cks.nice.org.uk/acute-kidney-injury#!scenario)
16. Proportion of patients developing pulmonary oedema [ Time Frame: 7 days ]
    Safety Radiology diagnosis or requirement for rescue management (new diuretic use)
17. Proportion of patients developing allergy or anaphylaxis [ Time Frame: 7 days ]
    Requirement for rescue management (antihistamines, adrenaline, intravenous fluids, steroid)
18. Health Related Quality of life (EQ-5D-5L Questionnaire) [ Time Frame: 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. 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.
19. Secondary care costs [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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.

Contacts and Locations

Contacts

Contact: Alasdair Gray; 01312421340; alasdair.gray@ed.ac.uk

Contact: Kat Oatey; 01316519913; abcsepsis.trial@ed.ac.uk

Sponsors and Collaborators

University of Edinburgh

Investigators

• Study Director: Alasdair Gray; University of Edinburgh

More Information

• Responsible Party: University of Edinburgh
• ClinicalTrials.gov Identifier: NCT04540094
• Other Study ID Numbers: AC20043
• First Posted: September 7, 2020
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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).
• Supporting Materials: Clinical Study Report (CSR); Analytic Code
• Time Frame: From 2023
• Access Criteria: Requests can be made by email to the Chief Investigator from 2023.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Edinburgh:

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

Additional relevant MeSH terms:

Sepsis; Toxemia; Emergencies; Disease Attributes; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation