Trial Outcomes & Findings for Feasibility of 5% Albumin Compared With Balanced Crystalloid, as Intravenous Fluid Resuscitation in Adult Patients With Sepsis, Presenting as an Emergency to Hospital (NCT NCT04540094)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

300 participants

Primary outcome timeframe

Approx 1 year

Results posted on

2024-10-04

Participant Flow

Participant milestones

Participant milestones
Measure	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. 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	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. 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.
Overall Study STARTED	150	150
Overall Study COMPLETED	150	150
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.	Total n=300 Participants Total of all reporting groups
Age, Continuous	70 years STANDARD_DEVIATION 15 • n=150 Participants	68 years STANDARD_DEVIATION 18 • n=150 Participants	69 years STANDARD_DEVIATION 16 • n=300 Participants
Sex: Female, Male Female	79 Participants n=150 Participants	70 Participants n=150 Participants	149 Participants n=300 Participants
Sex: Female, Male Male	71 Participants n=150 Participants	80 Participants n=150 Participants	151 Participants n=300 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Lactate	3 mmol/l STANDARD_DEVIATION 3 • n=150 Participants	3 mmol/l STANDARD_DEVIATION 2 • n=150 Participants	3 mmol/l STANDARD_DEVIATION 3 • n=300 Participants
National Early Warning Score (NEWS) Score	8 units on a scale STANDARD_DEVIATION 2.4 • n=150 Participants	8.3 units on a scale STANDARD_DEVIATION 2.7 • n=150 Participants	8.1 units on a scale STANDARD_DEVIATION 2.5 • n=300 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Recruitment Rate	150 Participants	150 Participants

PRIMARY outcome

Timeframe: 30 days

Assessment of how many participants in each arm died after 30 days to determine the effect size between the treatment groups.

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=147 Participants 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. 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	Intravenous Balanced Crystalloid n=149 Participants 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. 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.
30-day Mortality	31 Participants	22 Participants

SECONDARY outcome

Timeframe: 180 days

Feasibility Outcome assessing the number of participants who provided data for clinical primary outcome (30 day mortality)

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Data Completeness of Primary Outcome	147 Participants	149 Participants

SECONDARY outcome

Timeframe: Approx 1 year

Feasibility Outcomes assessing the number of participants who withdraw from study intervention and/or data collection

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Withdrawal From Study	3 Participants	1 Participants

SECONDARY outcome

Timeframe: 6 hours

Feasibility Outcome- number of patients who receive any other fluid apart from intervention or control in first 6 hrs after recruitment

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Patients Who Receive Any Other Fluid Apart From Intervention or Control in First 6 Hrs After Recruitment	33 Participants	1 Participants

SECONDARY outcome

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

Feasibility Outcome- Time to start of in-hospital intravenous fluids

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Time to Start of In-hospital Intravenous Fluids	41 minutes Interval 17.0 to 76.0	36 minutes Interval 17.0 to 63.0

SECONDARY outcome

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

Secondary Clinical Outcome

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
In-hospital Mortality	29 Participants	23 Participants

SECONDARY outcome

Timeframe: 90 days

Secondary Clinical Outcome

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
90-day Mortality	43 Participants	32 Participants

SECONDARY outcome

Timeframe: 6 hours

Secondary Clinical Outcome- Volume of randomised fluid delivered in each arm in the first 6hrs

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Volume of Randomised Fluid Delivered in Each Arm in the First 6hrs	750 ml Interval 500.0 to 1334.0	1250 ml Interval 1000.0 to 2000.0

SECONDARY outcome

Timeframe: 90 days

Secondary Clinical Outcome

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Length of Hospital Stay	12.7 days Standard Deviation 15.9	13.9 days Standard Deviation 19.3

SECONDARY outcome

Timeframe: 90 days

Secondary Clinical Outcome- Proportion of patients admitted to critical care (HDU/ICU)

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Proportion of Patients Admitted to Critical Care (HDU/ICU)	6 Participants	3 Participants

SECONDARY outcome

Timeframe: 90 days

Secondary Clinical Outcome- Length of stay in critical care (HDU/ICU)

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Length of Stay in Critical Care (HDU/ICU)	1.3 days Standard Deviation 5.9	1.5 days Standard Deviation 5.4

SECONDARY outcome

Timeframe: From time of Randomisation until time of hospital discharge, measured up to 90 days.

Secondary Clinical Outcome-number of participants needing intravenous vasopressors

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Participants Needing Intravenous Vasopressors	18 Participants	12 Participants

SECONDARY outcome

Timeframe: From time of Randomisation until time of hospital discharge, measured up to 90 days.

Secondary Clinical Outcome- Number of participants needing renal replacement

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Participants Needing Renal Replacement	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From time of Randomisation until time of hospital discharge, measured up to 90 days.

Secondary Clinical Outcome- Number of participants needing invasive ventilation

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Participants Needing Invasive Ventilation	7 Participants	4 Participants

SECONDARY outcome

Timeframe: 90 days

Secondary Clinical Outcome- Number of patients readmitted in first 90 days after discharge

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Patients Readmitted in First 90 Days After Discharge	20 Participants	21 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Patients Developing Acute Kidney Injury (AKI)	36 Participants	30 Participants

SECONDARY outcome

Timeframe: 7 days

Safety Radiology diagnosis or requirement for rescue management (new diuretic use)

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Patients Developing Pulmonary Oedema	22 Participants	11 Participants

SECONDARY outcome

Timeframe: 7 days

Requirement for rescue management (antihistamines, adrenaline, intravenous fluids, steroid)

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Number of Patients Developing Allergy or Anaphylaxis	0 Participants	1 Participants

SECONDARY outcome

Timeframe: baseline

Population: Health Related Quality of life questionnaires were applicable only to the first 50 participants who entered the study. As this is a self-reported questionnaire, participants may not be well enough to complete this at any given time-point.

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.

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=19 Participants 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. 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	Intravenous Balanced Crystalloid n=26 Participants 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. 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.
Health Related Quality of Life (EQ-5D-5L Questionnaire)	0.8 score on a scale Interval 0.2 to 0.9	0.5 score on a scale Interval 0.2 to 0.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours

Secondary Clinical Outcome-Volume of randomised fluid delivered in each arm in the first 24hrs

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=150 Participants 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. 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	Intravenous Balanced Crystalloid n=150 Participants 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. 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.
Volume of Randomised Fluid Delivered in Each Arm in the First 24hrs	1012 ml Standard Deviation 703	2209 ml Standard Deviation 1461

SECONDARY outcome

Timeframe: 7 Days

Population: Health Related Quality of life questionnaires were applicable only to the first 50 participants who entered the study. As this is a self-reported questionnaire, participants may not be well enough to complete this at any given time-point.

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.

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=19 Participants 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. 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	Intravenous Balanced Crystalloid n=27 Participants 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. 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.
Health Related Quality of Life (EQ-5D-5L Questionnaire)	0.4 score on a scale Interval 0.1 to 0.8	0.5 score on a scale Interval 0.2 to 0.7

SECONDARY outcome

Timeframe: 180 Days

Population: Health Related Quality of life questionnaires were applicable only to the first 50 participants who entered the study. As this is a self-reported questionnaire, participants may not be well enough to complete this at any given time-point.

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.

Outcome measures

Outcome measures
Measure	5% Human Albumin Solution n=20 Participants 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. 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	Intravenous Balanced Crystalloid n=28 Participants 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. 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.
Health Related Quality of Life (EQ-5D-5L Questionnaire)	0.4 units on a scale Interval 0.1 to 0.8	0.5 units on a scale Interval 0.2 to 0.7

Adverse Events

5% Human Albumin Solution

Serious events: 5 serious events

Other events: 25 other events

Deaths: 43 deaths

Intravenous Balanced Crystalloid

Serious events: 2 serious events

Other events: 20 other events

Deaths: 32 deaths

Serious adverse events

Serious adverse events
Measure	5% Human Albumin Solution n=150 participants at risk 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. 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	Intravenous Balanced Crystalloid n=150 participants at risk 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. 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.
General disorders General Disorders	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Gastrointestinal disorders Gastrointestinal Disorders	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Reproductive system and breast disorders Reproductive system and breast disorders	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Vascular disorders Vascular Disorders	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis

Other adverse events

Additional Information

Prof Alasdair Gray

University of Edinburgh

Phone: 0131 242 1340

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	5% Human Albumin Solution n=150 participants at risk 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. 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	Intravenous Balanced Crystalloid n=150 participants at risk 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. 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.
Blood and lymphatic system disorders Blood and Lymphatic	2.0% 3/150 • Number of events 3 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Cardiac disorders Cardiac Disorders	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Gastrointestinal disorders Gastrointestinal disorders	2.0% 3/150 • Number of events 3 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
General disorders General disorders and administration	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Infections and infestations Infections and infestations	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Investigations Investigations	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	3.3% 5/150 • Number of events 6 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Metabolism and nutrition disorders Metabolism and nutrition disorders	2.7% 4/150 • Number of events 7 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Nervous system disorders Nervous system disorders	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Renal and urinary disorders Renal and urinary disorders	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Reproductive system and breast disorders Reproductive system and breast disorders	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Surgical and medical procedures Surgical and medical procedures	0.00% 0/150 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis
Vascular disorders Vascular disorders	0.67% 1/150 • Number of events 1 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis	1.3% 2/150 • Number of events 2 • SAEs defined as outcome events were collected for 90 days. All other SAEs were collected for 7 days. All SAEs that meet the definition given in protocol section 11.1 and occur between consent and 7 days afterwards were recorded/reported to Sponsor. Outcome events are anticipated in this participant group were recorded for 90 days but exempt from reporting to the Sponsor: All-cause Death Death related to infection (including multi-organ failure) Critical care (HDU/ICU) admission Acute kidney injury Pulmonary oedema, Allergy or anaphylaxis