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Trial registered on ANZCTR

Registration number

ACTRN12615001282572

Ethics application status

Approved

Date submitted

19/11/2015

Date registered

25/11/2015

Date last updated

7/12/2020

Date data sharing statement initially provided

19/08/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Induced hypernatremia - a therapy for acute lung injury?

Scientific title

Effect of induced hypernatremia in patients with ARDS in addition to lung protective ventilation and conservative fluid management therapy, compared to lung protective ventilation and conservative fluid management therapy only, on lung injury score (LIS) and successful extubation

Secondary ID [1]

Nil Known

Universal Trial Number (UTN)

Trial acronym

HALT study

Linked study record

Health condition

Health condition(s) or problem(s) studied:

acute respiratory distress syndrome (ARDS) patient

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Administration of intravenous 20% saline to maintain serum sodium between 145 - 150 mmol /l for 7 days in addition to lung protective ventilation (in accordance with LOVS study; JAMA 2008;299:637-45 ie target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O- examined with by recording the tidal volume and plateau pressure every day,) and conservative fluid management therapy (in accordance with the conservative arm of the FACTT trial (N Engl J Med 2006; 354:2564-2575; with use of frusemide, restriction of fluid boluses aiming for a negative fluid balance- examined by recording the fluid balance every day )

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

ARDS patient -Lung protective ventilation and use of conservative fluid management therapy

lung protective ventilation (in accordance with LOVS study; JAMA 2008;299:637-45 ie target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O- examined with by recording the tidal volume and plateau pressure every day,) and conservative fluid management therapy (in accordance with the conservative arm of the FACTT trial (N Engl J Med 2006; 354:2564-2575; with use of frusemide, restriction of fluid boluses aiming for a negative fluid balance- examined by recording the fluid balance every day )

Control group

Active

Outcomes

Primary outcome [1]

Proportion of patients with a 1-point reduction in lung injury score (LIS), or successful extubation by day 7. as a composite outcome

Timepoint [1]

7 days

Secondary outcome [1]

Oxygenation index (OI) (OI= FiO2 X mean airway pressure/PaO2
Mean airway pressure - Lung ventilator data
PaO2 and FiO2 by recording the blood gases

Timepoint [1]

Every day till extubation (if earlier than 7 days) for the maximum of 7 days

Secondary outcome [2]

Inflammatory biomarkers (plasma and BAL) (CRP, TNF alpha, IL6, IL8, Ang 2, PLA2, TGF beta)

Timepoint [2]

Baseline , day 3 and day 7

Secondary outcome [3]

Plateau pressure - Lung ventilator data

Timepoint [3]

Every day till extubation (if earlier than 7 days) for the maximum of 7 days

Secondary outcome [4]

Static lung compliance- Lung ventilator data

Timepoint [4]

Every day till extubation (if earlier than 7 days) for the maximum of 7 days

Secondary outcome [5]

PaO2/FiO2 ratio
Data from the blood gases

Timepoint [5]

Every day till extubation (if earlier than 7 days) for the maximum of 7 days

Secondary outcome [6]

Sequential organ failure assessment (SOFA)score

Timepoint [6]

Every day till extubation (if earlier than 7 days) for the maximum of 7 days

Secondary outcome [7]

Ventilator free days
Outcome assessed by examining patient medical records

Timepoint [7]

Day 28

Secondary outcome [8]

Use of rescue therapy such as inhlaed NO,ECMO, Prone positioning
Outcome assessed by examining patient medical records

Timepoint [8]

Every day till extubation (if earlier than 7 days) for the maximum of 7 days

Secondary outcome [9]

ICU and hospital length of stay
Outcome assessed by examining patient medical records

Timepoint [9]

at discharge from ICU and at hospital discharge.

Secondary outcome [10]

ICU and hospital mortality
Outcome assessed by examining patient medical records

Timepoint [10]

up to hospital discharge.

Eligibility

Key inclusion criteria

ICU Patients more than equal to 16 years of age who are i) intubated, ii) within 48 hours of a diagnosis of ARDS (PaO2/FiO2 less than equal to 200 mmHg, PEEP = 5 cm H2O, bilateral opacities on chest Xray and respiratory failure not fully explained by cardiac failure or fluid overload) with a known respiratory risk factor for ARDS.

Minimum age

16 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Active bronchospasm or a history of significant chronic obstructive airway disease or asthma, moderate and severe traumatic brain injury, the presence of an intracranial pressure monitor, or any medical condition associated with a clinical suspicion of raised intracranial pressure, lack of consent (treating physician or next of kin), inevitable and imminent death, pregnancy,receiving ECMO, invlovement in other prospective clinical studies.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

sealed opaque envelopes

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Block randomisation with variable block size, stratified by site.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 1 / Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Statistical justification : We do not have any previous data for sample size calculation. This is a pilot study and our primary end point is similar to that used by Meduri et al (Chest. 2007;131:954-63); if we achieve similar kind of separation between the groups, with a power of 80% and alpha of less than 0.05 we will require 18 patients per group. To allow for contingencies, we aim to enrol 20 subjects per group.

Baseline and outcome variables will be compared using Chi-square tests for equal proportion, Student’s t-test for normally distributed outcomes and Wilcoxon rank-sum tests otherwise. Multivariate models adjusting for baseline imbalances and known covariates will be performed using logistic regression. In order to account for the longitudinal correlated nature of variables Generalized linear and repeated measures modelling will used to analyse each of the outcomes (primary and secondary). Multiple imputations and mixed modelling will be utilised if there is missing data.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/06/2016

Actual

5/10/2016

Date of last participant enrolment

Anticipated

1/09/2020

Actual

15/03/2020

Date of last data collection

Anticipated

Actual

1/07/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Flinders Medical Centre - Bedford Park

Recruitment postcode(s) [1]

5042 - Flinders University

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Intensive Care Foundation

Address [1]

level 2,10 Ievers Terrace, Carlton VIC 3053

Country [1]

Australia

Primary sponsor type

Individual

Name

Shailesh Bihari

Address

Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042

Country

Australia

Secondary sponsor category [1]

None

Name [1]

NONE

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee

Ethics committee address [1]

Flinders Medical
Centre
The Flats G5 –
Rooms 3 and 4
Flinders Drive,
Bedford Park
SA 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/02/2015

Approval date [1]

30/04/2015

Ethics approval number [1]

55.15 - HREC/15/SAC/50

Summary

Brief summary

Acute Respiratory Distress Syndrome (ARDS) is a severe form of lung damage that follows a variety of insults, most commonly infection. This is characterized by lung inflammation and flooding of airspaces within the lung by fluid leaking from the blood vessels. Patients with ARDS usually require life support from a breathing machine (ventilator). 
About 34% of patients suffering from ARDS die despite best care. At any given point about 6% of patients in all Australian ICUs are suffering from this disease. 
There is growing evidence to suggest that higher salt levels in the blood may have protective effect on lungs in ARDS. Higher salt concentrations in blood have been shown to reduce inflammatory damage to the lungs, less flooding of airspaces and improved function. However, these data are from isolated cell studies or experiments in non-human lungs. There is an urgent need to explore the beneficial effects of high salt concentration in blood in a controlled study in humans.
As a first step towards investigating the beneficial effect of a high blood salt concentration, we will randomize 40 patients with ARDS to either receive usual care or usual care with additional treatment to increase the salt concentration in blood. Higher salt concentrations in blood will be achieved by administering fluids with higher salt content and will be maintained up to 7 days. Daily assessments of lung function and severity of illness will be performed along with close monitoring of any adverse effects of high salt concentrations.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Shailesh Bihari

Address

Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042

Country

Australia

Phone

+618 82044247

Fax

+ 61 8 82045751

[email protected]

Contact person for public queries

Name

Shivesh Prakash

Address

Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042

Country

Australia

Phone

+618 82044247

Fax

+ 61 8 82045751

[email protected]

Contact person for scientific queries

Name

Shailesh Bihari

Address

Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042

Country

Australia

Phone

+618 82044247

Fax

+ 61 8 82045751

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Single centre study and not planned

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
3992	Study protocol			[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Induced hypernatremia in patients with moderate-to-severe ARDS: a randomized controlled study.	2021	https://dx.doi.org/10.1186/s40635-021-00399-3

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically