Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000948695
Ethics application status
Approved
Date submitted
26/08/2014
Date registered
4/09/2014
Date last updated
10/12/2018
Date data sharing statement initially provided
10/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
SIGNal peptides Indicative For Immediate Cardiac and Anti-pneumonic Treatment in acute Heart Failure
Scientific title
Evaluating the effectiveness of signal peptides in diagnosing pneumonia and heart failure in patients who present with acute shortness of breath.
Secondary ID [1] 285227 0
Nil known
Universal Trial Number (UTN)
U1111-1160-8940
Trial acronym
SIGNIFICANT-HF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Heart Failure 292857 0
pneumonia 292858 0
Condition category
Condition code
Cardiovascular 293157 293157 0 0
Coronary heart disease
Infection 293186 293186 0 0
Other infectious diseases
Respiratory 293187 293187 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We will recruit 2000 patients presenting to the Emergency Department (ED) of Christchurch Hospital with the primary complaint of breathlessness.

Blood samples will be taken at presentation in the ED, at 24 hours and at discharge to test the diagnostic performance of Ghrelin signal peptide (GHRsp) and Neutrophil gelatinase associated lipocalin signal peptide (NGALsp) against and alongside N-terminal of the prohormone brain natriuretic peptide (NTproBNP) and procalcitonin (PCT) for the diagnosis of pneumonia, HF and concurrent pneumonia and HF.

Patients will be followed up at 30 and 90 days and 1 year to allow for assessment of prognostic power of GHRsp and NGALsp to predict subsequent events.All diagnoses will undergo standardised adjudication by two clinicians blinded to marker results.
Intervention code [1] 290103 0
Not applicable
Comparator / control treatment
n/a
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293015 0
Serum assay results will be used to assess the performance of signal peptides in early detection of pneumonia complicating Acute Decompensated Heart Failure (ADHF)
Timepoint [1] 293015 0
30, 90 and 365 days
Secondary outcome [1] 310155 0
Serum assay results will be used to identify a superior marker with the potential to be tested in a study of marker guidance of early antibiotic treatment in complicated ADHF.
Timepoint [1] 310155 0
outcome assessed at 30, 90 and 365 days by serum assay
Secondary outcome [2] 310298 0
The prognostic utility of markers for all-cause mortality
Timepoint [2] 310298 0
30, 90 and 365 days by data linkage to patient medical records
Secondary outcome [3] 310299 0
readmission with HF, pneumonia or other infection
Timepoint [3] 310299 0
30, 90 and 365 days by data linkage to patient medical records to adjudicate readmission discharge diagnoses
Secondary outcome [4] 310300 0
all cardiovascular and infectious events and all readmissions
Timepoint [4] 310300 0
30, 90 and 365 days by data linkage to patient medical records to adjudicate readmission discharge diagnoses

Eligibility
Key inclusion criteria
Eligible patients who report shortness of breath not due to trauma as their primary complaint upon presentation to the ED.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients under 18 years of age or unable to provide consent are excluded.
Patients with an acute ST-elevation myocardial infarction and patients on haemodialysis for renal failure are also excluded.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Based on current enrolment data (n=500), we anticipate that of the 1200, approximately 13% (~160) will have pneumonia and ~2.5% (~30) will have concurrent ADHF and pneumonia. On the basis of our data a sample size of 30 for the combination diagnosis group (the smallest of the groups) will provide sufficient power (>90%) to detect ROC AUCs >0.75 as statistically significant (two-tailed alpha=0.05). The test performance of each marker to diagnose pneumonia, ADHF and co-existing pneumonia/ADHF will be assessed by AUCs of the ROC curves and calculation of sensitivity, specificity, positive and negative predictive values and overall accuracy for specific cut-points. The prognostic utility of markers for all-cause mortality, readmission with HF, pneumonia or other infection, all cardiovascular and infectious events and all readmissions at 30, 90 and 365 days will be examined using Kaplan-Meier curves with groups defined by ROC curve- derived “optimal” cut-points and with multivariate analysis using Cox Proportional hazards regressions using a base model incorporating standard clinical predictors of outcome with rotation of single and multiple candidate markers through the model to test for independent predictors of these outcomes.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/07/2007
Actual
20/07/2007
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1200
Accrual to date
766
Final
Recruitment outside Australia
Country [1] 6309 0
New Zealand
State/province [1] 6309 0
Christchurch

Funding & Sponsors
Funding source category [1] 289839 0
Government body
Name [1] 289839 0
Health Research Council
Country [1] 289839 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] 288529 0
None
Name [1] 288529 0
Address [1] 288529 0
Country [1] 288529 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291572 0
NZ Health & Disability Ethics Committees
Ethics committee address [1] 291572 0
1 The Terrace
Wellington Central
Wellington 6011
Ethics committee country [1] 291572 0
New Zealand
Date submitted for ethics approval [1] 291572 0
23/02/2007
Approval date [1] 291572 0
11/04/2007
Ethics approval number [1] 291572 0
URB/07/03/011

Summary
Brief summary
There is a pressing need for additional tools to help differentiate heart failure from other causes of dyspnea in acutely short of breath patients, and to improve our ability to provide accurate prognostic information and sound therapeutic management to heart failure patients. Where ADHF is the primary cause of dyspnoea, plasma BNP is a proven diagnostic adjunct. However, where pneumonia and ADHF co-exist, lack of specific pneumonic findings can delay appropriate introduction of antibiotic therapy. Misdiagnosis or delay in the introduction of appropriate therapy leads to significant morbidity and mortality from respiratory/circulatory failure and septicaemia. There is a need for biomarkers that can; 1) assist in the rapid diagnosis of pneumonia in ADHF, 2) assist in the prediction of who may be at risk of serious pneumonia-related complications and 3) aid the decision to administer antibiotic therapy where there is suspicion of pneumonia present in ADHF.
The SIGNIFICANT-HF Study is an initiative to assess a new and unique biological markers in an acute shortness of breath population. 1200 people presenting to the Christchurch Hospital Emergency Department with non-traumatic shortness of breath will be invited to participate. 3 additional blood samples will be collected during admission for analysis of the levels of these newly identified heart hormones.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50950 0
Prof Mark Richards
Address 50950 0
Christchurch Heart Institute
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 50950 0
New Zealand
Phone 50950 0
+643 364 0640
Fax 50950 0
+643 364 1115
Email 50950 0
mark.richards@cdhb.health.nz
Contact person for public queries
Name 50951 0
Ms Lorraine Skelton
Address 50951 0
Christchurch Heart Institute
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 50951 0
New Zealand
Phone 50951 0
+643 364 1063
Fax 50951 0
+643 364 1115
Email 50951 0
lorraine.skelton@cdhb.health.nz
Contact person for scientific queries
Name 50952 0
A/Prof Chris Pemberton
Address 50952 0
Christchurch Heart Institute
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 50952 0
New Zealand
Phone 50952 0
+643 364 0887
Fax 50952 0
+643 3640818
Email 50952 0
chris.pemberton@otago.ac.nz

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.