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Trial registered on ANZCTR


Registration number
ACTRN12613000921785
Ethics application status
Approved
Date submitted
14/08/2013
Date registered
20/08/2013
Date last updated
8/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The Which Heart failure Intervention is most Cost-effective in reducing Hospital stay (WHICH? II) trial.
Scientific title
A pragmatic multicentre randomised control trial comparing intensive nurse-led intervention management and standard heart failure care by local heart failure services on reducing the cost of health care in hospitalised patients with chronic heart failure.
Secondary ID [1] 282912 0
Nil
Universal Trial Number (UTN)
U1111-1146-7324
Trial acronym
WHICH? II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 289723 0
Condition category
Condition code
Cardiovascular 290051 290051 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Initial profiling of subjects to determine incremental risk of rehospitalisation or death using the Green Amber Red Delineation of Individual risk And Need in Heart Failure (GARDIAN-HF) tool.

Based on subject location (metropolitan or remote dwelling) and GARDIAN-HF profiling, subjects will be exposed to a more intensive, nurse-led management program (including incremental face-to-face visits and structured telephone support), and monitoring of BNP levels using a point of care machine (for those aged younger than 75 years at the date of index hospitalisation) for a minimum of 12 months post index discharge. Active surveillance and management will continue for a minimum of 12 months for major endpoint analyses and then up to 5 years to determine the longer-term effects of the study intervention.

The incremental face-to-face visits include a full physical assessment (i.e. lying and standing blood pressure, pulse, heart sounds, oedema, etc), symptom assessment (i.e. NYHA class, dyspnoea and appetite/evidence of cachexia or malnutrition), and compliance with clinical monitoring and self-management (i.e. daily weighs, fluid intake assessment, and medication adherence), ongoing HF self-management education, assessment of self-care behaviours (i.e. attendance to GP/ Cardiologist, emotional levels, immunisation status and health-related quality of life) and a plan of future care including medication titration and ordering of further tests (i.e. pathology, x-ray), in consultation with the individuals health care team, communication with GP, and/or referral to community services or allied health professionals.

The structured telephone support includes a range of pre-determined questions including presence of symptoms (shortness of breath, or weight increase), length of symptoms, and maintenance of low sodium diet and fluid restriction.

The individuals who are randomly allocated into the intensive management arm of the study will receive at least two home visits throughout the initial 12 month follow-up period. All intensive management patients will also receive weekly to monthly structured telephone support by the National Heart Foundation of Australia (NHFA). Those participants who are designated into standard care and live remotely from the hospital (i.e. greater than 30km’s from the recruitment site) will receive monthly structured telephone support from the NHFA.

Each home visit will take a minimum of 60 minutes. The initial structured telephone support call will take approximately 20 minutes for the initial call and approximately 8 minutes for each call thereafter.

Detailed reports of initial profiling and management will be sent to the subject's heath care team (i.e. GP) utilising the GARDIAN-HF tool.
Intervention code [1] 287606 0
Other interventions
Comparator / control treatment
Standard heart failure treatment as provided by the subject's local heart failure service including pre-discharge planning, formal pathways to improve communication within the health care team, optimisation of gold-standard pharmacological therapy (including up-titration of doses to evidence-based levels), application of non-pharmacological strategies – including access to formal/informal exercise programs, monitoring weight and adjusting dietary intake, patient (and caregiver) education, promotion of self-care, and increased surveillance for impending crises. At least one home visit will be performed.
Control group
Active

Outcomes
Primary outcome [1] 290103 0
Total cost of health care (calculated as cost/day per subject). Assessed via linked data from hospital/death records, GP follow-up and participant feedback.
Timepoint [1] 290103 0
12 Months post index hospital discharge
Secondary outcome [1] 303950 0
Rate of hospitalisation (all-cause, unplanned, CVD and CHF-specific) both in respect to hospital episodes and associated length of stay. This is measured as events per patient per 100 days.

Australia-refined Diagnostic Related Groupings (AR-DRGs) will be used to standardise and categorise each hospital readmission into fixed and variable costs. Fixed costs are those that all surviving patients incur irrespective of their length of stay, whilst variable costs are a per diem (i.e. medical and nursing staff) cost and are dependent on the length of stay. The total costs are the variable costs multiplied by the length of stay plus the fixed cost.
Timepoint [1] 303950 0
12 Months post index hospital discharge
Secondary outcome [2] 303951 0
All-cause mortality. Assessed via linked data from the local death registry.
Timepoint [2] 303951 0
12 Months post index hospital discharge
Secondary outcome [3] 303952 0
Event-free survival from all-cause death or hospitalisation - measured as both a dichotomous variable (yes or no) and expressed as days alive and out-of-hospital.

Assessed via linked data from hospital/death records, GP follow-up and participant feedback.
Timepoint [3] 303952 0
12 Months post index hospital discharge
Secondary outcome [4] 303953 0
Change in health-related quality of life from baseline to 12 months:

Generic (AQoL-8D) and;
Heart failure specific (Kansas City Cardiomyopathy Questionnaire)
Timepoint [4] 303953 0
12 Months post index hospital discharge.
Secondary outcome [5] 303954 0
Pattern of gold-standard therapy (including prescribed doses of angiotensin converting enzyme [ACE] inhibitors and beta blockers) relative to expert guidelines for the management of chronic heart failure.

Assessed during the clinic visit at the 12 month time-point via medical records, GP records, and patient review.
Timepoint [5] 303954 0
12 Months post index hospital discharge.
Secondary outcome [6] 304157 0
Prolonged follow-up of event-free survival from all-cause death or hospitalisation - measured as both a dichotomous variable (yes or no) and expressed as days alive and out-of-hospital.

Assessed via linked data from hospital/death records, GP follow-up and participant feedback.
Timepoint [6] 304157 0
5 Years post index hospital discharge.

Eligibility
Key inclusion criteria
Individuals discharged to home following an admission to a participating hospital will be eligible for study randomisation if they: 1) have a diagnosis of chronic heart failure and 2) a history of 1 or more admissions to hospital with acute HF (including the index hospitalisation).
Minimum age
0 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they have a terminal condition, are non-English speaking and unable to give fully informed consent (in the absence of an interpreter) and/or unable to give fully informed consent for another reason.

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)
All patients with a cardiac diagnosis admitted to four hospitals in SA (The Queen Elizabeth Hospital, Adelaide), NSW (St Vincent's Hospital and Prince of Wales Hospital, Sydney) and VIC (The Western Hospital, Melbourne) will be screened for study eligibility.

Dedicated recruitment staff will monitor hospital cardiac units for patients who fit the eligibility criteria. Once a patient consents, the recruiters will call the data management department at the Mary MacKillop Institute for Health Research, Australian Catholic University on a toll-free 1800-number to complete randomisation. The recruiter will be asked for the patients initials, metropolitan versus rural living status, and type of HF (preserved versus impaired systolic function) for stratification of participants.

Once this data has been entered into the Mary MacKillop Institute for Health Research system, a unique ID code will be generated with the participant's randomised group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random, computer generated sequence with block randomisation for each participating hospital.

Randomisation will be stratified according to 2 criteria:

1) Presence/absence of impaired versus preserved left ventricular ejection fraction (systolic function).

2) Participant location of residence in metropolitan areas -defined by each centre’s pre-defined catchment area for face-to-face management (default less than 30km and/or 45 minutes travel time to patients’ home) or beyond.

Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Complies with CONSORT guidelines for a pragmatic, randomised trial of a health service intervention.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
All baseline and outcome data will be analysed on an intention-to-treat basis.

Continuous data will be presented as a mean +/- standard deviation or median plus interquartile range. Categorical data will be presented as a percentage. Univariate comparisons of baseline data will involve Chi square analyses (with calculation of odds ratios and 95% CIs for categorical data), Mann Whitney U test for non-normally distributed continuous data (including the rate of health care costs and hospital stay) and Student’s t-test for normally distributed continuous data.

All-cause mortality and event-free survival data will be initially analysed using Life Tables and Kaplan Meier survival curves. Days alive out-of- hospital will be calculated as days of survival (of maximal days of survival) free from all-cause hospitalization.

Cox proportional hazards models (including demographic and clinical data) will examine the independent impact of group allocation on event-free survival and all-cause mortality. If study outcomes are highly skewed Poisson Regression Analyses will be undertaken by the study statistician.

Detailed health economic analyses will be derived and informed from initial analyses of primary and secondary endpoint data.

Initial study power estimates:

Based on data from the original WHICH? Trial data and 1:1 randomization this study will have greater than 85% power (two-sided alpha of 0.05), a total of 400 patients in each group (800 in total) to detect a minimum 15% absolute difference in the primary endpoint - total health care costs (expected rate of $90 +/- 100 per day/patient in the standard management group) within 12 months of follow-up (a shorter follow-up than was originally planned). On the same basis, we will have sufficient power to detect a 15% absolute difference in total hospital stay (expected rate of 1.74 +/- 3.1 days per patient).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/08/2013
Actual
2/09/2013
Date of last participant enrolment
Anticipated
1/01/2016
Actual
31/01/2016
Date of last data collection
Anticipated
Actual
3/02/2017
Sample size
Target
800
Accrual to date
Final
787
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 1357 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 1358 0
Western Hospital - Footscray
Recruitment hospital [3] 1359 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [4] 5788 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 7216 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 7217 0
3011 - Footscray
Recruitment postcode(s) [3] 7218 0
5011 - Woodville
Recruitment postcode(s) [4] 13229 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 287689 0
Government body
Name [1] 287689 0
National Health and Medical Research Council
(Project grant 1049133)
Country [1] 287689 0
Australia
Primary sponsor type
Individual
Name
Professor Simon Stewart
Address
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne
VIC 3000
Country
Australia
Secondary sponsor category [1] 286422 0
Individual
Name [1] 286422 0
Associate Professor Melinda Carrington
Address [1] 286422 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne
VIC 3000
Country [1] 286422 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289648 0
Human Research Ethics Committee (TQEH/LMH/MH)
Ethics committee address [1] 289648 0
Ethics committee country [1] 289648 0
Australia
Date submitted for ethics approval [1] 289648 0
21/05/2013
Approval date [1] 289648 0
20/06/2013
Ethics approval number [1] 289648 0
HREC/13/TQEHLMH/99
Ethics committee name [2] 289649 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [2] 289649 0
Ethics committee country [2] 289649 0
Australia
Date submitted for ethics approval [2] 289649 0
12/06/2013
Approval date [2] 289649 0
29/07/2013
Ethics approval number [2] 289649 0
2013.145
Ethics committee name [3] 289650 0
St Vincent's Hospital Research Ethics Committee
Ethics committee address [3] 289650 0
Ethics committee country [3] 289650 0
Australia
Date submitted for ethics approval [3] 289650 0
Approval date [3] 289650 0
12/11/2013
Ethics approval number [3] 289650 0
Ethics committee name [4] 295006 0
South Eastern Sydney Local Health District
Ethics committee address [4] 295006 0
Ethics committee country [4] 295006 0
Australia
Date submitted for ethics approval [4] 295006 0
17/02/2014
Approval date [4] 295006 0
08/04/2014
Ethics approval number [4] 295006 0
14/G/076

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41766 0
Prof Simon Stewart
Address 41766 0
The Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne VIC 3000
Country 41766 0
Australia
Phone 41766 0
+61 3 99533677
Fax 41766 0
Email 41766 0
simon.stewart@acu.edu.au
Contact person for public queries
Name 41767 0
Simon Stewart
Address 41767 0
The Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne VIC 3000
Country 41767 0
Australia
Phone 41767 0
+61 3 99533677
Fax 41767 0
Email 41767 0
MacKillopInstitute.WHICH2@acu.edu.au
Contact person for scientific queries
Name 41768 0
Simon Stewart
Address 41768 0
The Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne VIC 3000
Country 41768 0
Australia
Phone 41768 0
+61 3 99533677
Fax 41768 0
Email 41768 0
Simon.Stewart@acu.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCharacteristics of symptoms and symptom change across different heart failure subtypes: a sex-stratified analysis.2023https://dx.doi.org/10.1093/eurjcn/zvac099
N.B. These documents automatically identified may not have been verified by the study sponsor.