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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
Date results information initially provided
7/12/2020
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] 287941 0
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 296821 0
Condition category
Condition code
Respiratory 297051 297051 0 0
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] 293290 0
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] 296652 0
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] 296652 0
7 days
Secondary outcome [1] 319000 0
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] 319000 0
Every day till extubation (if earlier than 7 days) for the maximum of 7 days
Secondary outcome [2] 319043 0
Inflammatory biomarkers (plasma and BAL) (CRP, TNF alpha, IL6, IL8, Ang 2, PLA2, TGF beta)
Timepoint [2] 319043 0
Baseline , day 3 and day 7
Secondary outcome [3] 319044 0
Plateau pressure - Lung ventilator data
Timepoint [3] 319044 0
Every day till extubation (if earlier than 7 days) for the maximum of 7 days
Secondary outcome [4] 319045 0
Static lung compliance- Lung ventilator data
Timepoint [4] 319045 0
Every day till extubation (if earlier than 7 days) for the maximum of 7 days
Secondary outcome [5] 319046 0
PaO2/FiO2 ratio
Data from the blood gases
Timepoint [5] 319046 0
Every day till extubation (if earlier than 7 days) for the maximum of 7 days
Secondary outcome [6] 319047 0
Sequential organ failure assessment (SOFA)score
Timepoint [6] 319047 0
Every day till extubation (if earlier than 7 days) for the maximum of 7 days
Secondary outcome [7] 319048 0
Ventilator free days
Outcome assessed by examining patient medical records
Timepoint [7] 319048 0
Day 28
Secondary outcome [8] 319049 0
Use of rescue therapy such as inhlaed NO,ECMO, Prone positioning
Outcome assessed by examining patient medical records
Timepoint [8] 319049 0
Every day till extubation (if earlier than 7 days) for the maximum of 7 days
Secondary outcome [9] 319050 0
ICU and hospital length of stay
Outcome assessed by examining patient medical records
Timepoint [9] 319050 0
at discharge from ICU and at hospital discharge.
Secondary outcome [10] 319051 0
ICU and hospital mortality
Outcome assessed by examining patient medical records
Timepoint [10] 319051 0
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?
No
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
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 4690 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 12265 0
5042 - Flinders University

Funding & Sponsors
Funding source category [1] 292425 0
Charities/Societies/Foundations
Name [1] 292425 0
Intensive Care Foundation
Country [1] 292425 0
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] 291113 0
None
Name [1] 291113 0
NONE
Address [1] 291113 0
None
Country [1] 291113 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293885 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 293885 0
Flinders Medical
Centre
The Flats G5 –
Rooms 3 and 4
Flinders Drive,
Bedford Park
SA 5042
Ethics committee country [1] 293885 0
Australia
Date submitted for ethics approval [1] 293885 0
05/02/2015
Approval date [1] 293885 0
30/04/2015
Ethics approval number [1] 293885 0
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 61690 0
Dr Shailesh Bihari
Address 61690 0
Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042
Country 61690 0
Australia
Phone 61690 0
+618 82044247
Fax 61690 0
+ 61 8 82045751
Email 61690 0
[email protected]
Contact person for public queries
Name 61691 0
Dr Shivesh Prakash
Address 61691 0
Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042
Country 61691 0
Australia
Phone 61691 0
+618 82044247
Fax 61691 0
+ 61 8 82045751
Email 61691 0
[email protected]
Contact person for scientific queries
Name 61692 0
Dr Shailesh Bihari
Address 61692 0
Dept of ICCU, Flinders Medical Centre , Flinders Lane, Bedford Park SA 5042
Country 61692 0
Australia
Phone 61692 0
+618 82044247
Fax 61692 0
+ 61 8 82045751
Email 61692 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Single centre study and not planned


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
3992Study protocol  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseInduced hypernatremia in patients with moderate-to-severe ARDS: a randomized controlled study.2021https://dx.doi.org/10.1186/s40635-021-00399-3
N.B. These documents automatically identified may not have been verified by the study sponsor.