Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001030662
Ethics application status
Approved
Date submitted
11/09/2014
Date registered
25/09/2014
Date last updated
12/11/2018
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised clinical trial comparing peri-discharge management of Acute Decompensated Heart Failure with usual clinical care in terms of rates of death, rates of hospitalisation, health care utilisation, and cost-effectiveness.
Scientific title
A randomised clinical trial comparing peri-discharge management of Acute Decompensated Heart Failure with usual clinical care in terms of rates of death, rates of hospitalisation, health care utilisation, and cost-effectiveness.
Secondary ID [1] 285321 0
nil
Universal Trial Number (UTN)
U1111-1157-8380
Trial acronym
The IMPERATIVE-HF trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 293036 0
Condition category
Condition code
Cardiovascular 293308 293308 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
450 eligible patients admitted with Acute Decompensated Heart Failure (ADHF) will be enrolled and randomised to Natruiretic Peptide (NP)-guided group with treatment adjusted if NP levels are raised, or standard clinically-guided care. Baseline tests including NP levels will be measured by a blood tests at admission and then repeated on the day of discharge. Day of discharge will be determined by the attending physician and care will be transferred to the research team at point of discharge for the NP group to manage follow up visits. Pre-discharge NP levels will only be available for patients randomised to the NP group. Off-label measurement of NP levels outside of guidelines approved indications, will be discouraged and prohibited by study design in both study groups. Patients randomised to usual care will be managed according to usual ADHF care. Patients in the NP group will receive management guided by NP levels. All study participants will be monitored for treatment adherence by phone or in person visits at 2 days, 2, 6 & 12 weeks and additional visits will be arranged as required.
NP group - As for usual care but for patients with NTproBNP >1000pg/ml prior to discharge, delay of discharge for 24hrs will be considered to optimise diuretic and other HF therapy. After discharge, NP levels will be measured during HF nurse review at home within 2 days of discharge. Patients with NT-proBNP >1000pg/ml will receive alternate day telephone contact, weekly in-home HF nurse clinical review and 2-weekly HF clinic visits until NTproBNP <1000pg/ml. NTproBNP / estimated glomerular filtration rate (eGFR) testing will be performed at least weekly to guide up-titration of HF treatment – including increased diuretic dose if congestion or volume overload present, addition of spironolactone, alternate up-titration of ACE inhibitor and beta-blocker doses on a weekly basis.
The overall duration of the intervention period is 12 weeks.
Patients screened but not randomised to a treatment group will be included in a registry. Patients recorded in the registry but not randomised to a treatment arm will have no further interaction with the research team and care will continue as determined by their clinical team. Outcome data will be collected for registry patients to allow comparison with the study cohort.
Intervention code [1] 290232 0
Treatment: Other
Comparator / control treatment
Usual Care as per current standard of care pathways at Christchurch & Auckland Hospitals.
Management: Usual care group – patients will receive usual care for ADHF including in-hospital education about HF, weight self-monitoring, low salt diet, an exercise program, review in primary care and HF clinic within 2 weeks of discharge, coordinated input from district nursing and allied health at discretion of attending physician to ensure adequate support and housing, optimisation of medications according to HF guidelines. Further clinic follow-up will be guided by assessment at the 2-week visit.
Control group
Active

Outcomes
Primary outcome [1] 293143 0
Time to first Heart Failure readmission or all cause death within 90 days
Timepoint [1] 293143 0
90 days
Secondary outcome [1] 310440 0
Time to first Heart Failure readmission or all cause death within 180 days
Timepoint [1] 310440 0
180 days
Secondary outcome [2] 310441 0
Time to first Heart Failure readmission within 30 days; within 90 days; and within 180 days.
Timepoint [2] 310441 0
within 30 days; within 90 days; and within 180 days.
Secondary outcome [3] 310549 0
Time to all cause death within 30 days; within 90 days; and within 180 days
Timepoint [3] 310549 0
within 30 days; within 90 days; and within 180 days

Eligibility
Key inclusion criteria
Patients aged >18 year, living independently and able to provide informed consent, admitted with ADHF as evidenced by typical clinical features plus either radiological evidence of Heart Failure or an NTproBNP level >1000pg/ml.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A primary diagnosis of acute coronary syndrome (ACS), myocarditis/pericarditis, pericardial constriction, a life expectancy due to non-cardiac disease of <6 months, concurrent severe hepatic or pulmonary disease ,severe renal impairment (plasma creatinine >250 micro mol/L), severe valvular disease requiring surgery, severe aortic stenosis (valve area <1cm^2), or HF due to mitral stenosis, or a patient under consideration for cardiac transplantation

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A computer generated randomisation sequence arranged in permuted blocks will be generated prior to any recruitment. Once a patient has met inclusion/exclusion criteria and given written informed consent, the next sequential randomisation envelope will be opened. Randomisation will be stratified above and below 75 years of age.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation sequence arranged in permuted blocks
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Primary and secondary clinical outcomes will be analysed on an intention to treat basis as time-to-event data using Cox proportional hazards regression models. Health care utilisation over 90 days including all hospital admissions and lengths of stay, nurse visits, clinical tests, clinician times and therapy costs will be summarized individually and totaled for each patient to allow a comparison between NP-guided and usual care groups to determine their relative cost-effectiveness.

Sample Size and Power Analysis : based on an expected 90-day event rate of 35% a cohort of 450 patients will provide 80% power to show a 33% reduction in this event rate in the BNP-guided group and 90% power to show a 40% reduction, with a two-tailed alpha level of 0.05'.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/11/2014
Actual
18/11/2014
Date of last participant enrolment
Anticipated
31/12/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
450
Accrual to date
300
Final
Recruitment outside Australia
Country [1] 6349 0
New Zealand
State/province [1] 6349 0
Christchurch
Country [2] 6350 0
New Zealand
State/province [2] 6350 0
Auckland

Funding & Sponsors
Funding source category [1] 289942 0
Government body
Name [1] 289942 0
Health Research Council
Country [1] 289942 0
New Zealand
Funding source category [2] 294098 0
Charities/Societies/Foundations
Name [2] 294098 0
Heart Foundation of New Zealand
Country [2] 294098 0
New Zealand
Primary sponsor type
University
Name
Christchurch Heart Institute. University of Otago
Address
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 292930 0
None
Name [1] 292930 0
Address [1] 292930 0
Country [1] 292930 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291656 0
Health and Disability Ethics Committee
Ethics committee address [1] 291656 0
1 The Terrace
Wellington Central
Wellington 6011
Ethics committee country [1] 291656 0
New Zealand
Date submitted for ethics approval [1] 291656 0
10/09/2014
Approval date [1] 291656 0
21/10/2014
Ethics approval number [1] 291656 0
14/CEN/147

Summary
Brief summary
450 eligible patients admitted with ADHF will be enrolled and randomised to NP-guided or clinically-guided care. Baseline tests including NP levels will be measured at admission and then repeated on the day of discharge. Day of discharge will be determined by the attending physician and care will be transferred to the research team at point of discharge. Pre-discharge NP levels will only be available for patients randomised to the NP group. Off-label measurement of NP levels outside of guidelines approved indications, will be discouraged and prohibited by study design in both study groups. Patients randomised to usual care will be managed according to usual ADHF care. Patients in the BNP group will receive management guided by NP levels
Management: Usual care group – patients will receive usual care for ADHF including in-hospital education about HF, weight self-monitoring, low salt diet, an exercise program, review in primary care and HF clinic within 2 weeks of discharge, coordinated input from district nursing and allied health at discretion of attending physician to ensure adequate support and housing, optimisation of medications according to HF guidelines. Further clinic follow-up will be guided by assessment at the 2-week visit.
NP group - As for usual care but for patients with NTproBNP >1000pg/ml prior to discharge, delay of discharge for 24hrs will be considered to optimise diuretic and other HF therapy. After discharge, NP levels will be measured during HF nurse review at home within 2 days of discharge. Patients with NT-proBNP >1000pg/ml will receive alternate day telephone contact, weekly in-home HF nurse clinical review and 2-weekly HF clinic visits until NTproBNP <1000pg/ml. NTproBNP / estimated glomerular filtration rate (eGFR) testing will be performed at least weekly to guide up-titration of HF treatment – including increased diuretic dose if congestion or volume overload present, addition of spironolactone, alternate up-titration of ACE inhibitor and beta-blocker doses on a weekly basis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51382 0
Prof Richard Troughton
Address 51382 0
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 51382 0
New Zealand
Phone 51382 0
+643 364 0640
Fax 51382 0
+643 364 1115
Email 51382 0
[email protected]
Contact person for public queries
Name 51383 0
Ms Lorraine Skelton
Address 51383 0
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 51383 0
New Zealand
Phone 51383 0
+643 364 1063
Fax 51383 0
+643 364 1115
Email 51383 0
[email protected]
Contact person for scientific queries
Name 51384 0
Prof Richard Troughton
Address 51384 0
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 51384 0
New Zealand
Phone 51384 0
+643 364 0640
Fax 51384 0
+643 364 1115
Email 51384 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.