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Trial registered on ANZCTR


Registration number
ACTRN12616000452493
Ethics application status
Approved
Date submitted
25/09/2015
Date registered
7/04/2016
Date last updated
7/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Frailty and health outcomes in older people initiating an oral anticoagulant
Scientific title
A prospective multicentre cohort study on the influence of frailty on health outcomes in older people initiating an oral anticoagulant
Secondary ID [1] 287546 0
Nil
Universal Trial Number (UTN)
U1111-1174-8816
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation 296318 0
thromboembolism 296319 0
stroke 296320 0
haemorrhage 296321 0
Condition category
Condition code
Cardiovascular 296595 296595 0 0
Other cardiovascular diseases
Blood 296596 296596 0 0
Other blood disorders
Stroke 296597 296597 0 0
Ischaemic

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients who are commencing therapy with an anticoagulant (either warfarin or the novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban) will be followed up for 36 months or until cessation of the anticoagulant or death.
Intervention code [1] 292944 0
Not applicable
Comparator / control treatment
not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296207 0
Time to first episode of major haemorrhage or clinically relevant non-major haemorrhage.
Major haemorrhage will be defined according to the International Society of Thrombosis and Haemostasis and (ISTH) definition of:
a. Fatal bleeding and/or
b. Symptomatic bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, or pericardial, or intramuscular with compartment syndrome and/or
c. Bleeding causing a fall in haemoglobin level of 20g/L or more or leading to transfusion of two or more units of whole blood or red cells.

Clinically relevant non-major bleeding will be defined according to the ISTH definition of any sign or symptom of clinically overt bleeding that does not meet the criteria for major bleed but requires medical attention, including at least one of the following:
a. Medical intervention by a healthcare professional,
b. Hospitalisation or increased level of care,
c. Face to face evaluation by a clinician
Examples of clinically relevant non-major bleeding include macroscopic haematuria requiring intervention, epistaxis that requires tamponade or medical intervention, haemoptysis, hematemesis or rectal bleeding which requires endoscopy or other medical intervention.

Diagnostic codes for haemorrhage will be used to identify cases in accord with the International Classification of Diseases (ICD)-10AM from hospital medical records, follow-up phone calls to patients and/or their GP meeting the above pre-defined criteria.
Timepoint [1] 296207 0
Participants will be followed for 36 months from initiation of an oral anticoagulant or will be censored at primary outcome, cessation of oral anticoagulant or death.
Primary outcome [2] 296208 0
Time to first hospitalisation for stroke or VTE.
Diagnostic codes for stroke, deep vein thrombosis or pulmonary embolism will be used to identify cases in accord with ICD-10AM from hospital medical record, follow-up telephone interview with patients and/or their GP
Timepoint [2] 296208 0
Participants will be followed for 36 months from initiation of an oral anticoagulant or will be censored at primary outcome, cessation of oral anticoagulant or death.
Secondary outcome [1] 317814 0
Time to death. this will be determined from medical records or national death index-AIHW
Timepoint [1] 317814 0
Participants will be followed for 36 months from initiation of an oral anticoagulant or will be censored at primary outcome, cessation of oral anticoagulant or death.
Secondary outcome [2] 317815 0
The median duration of persistence with oral anticoagulants will be determined by frailty status accounting for death. This will be determined from medical record, pharmacy records, interview with patients and/or their GP
Timepoint [2] 317815 0
Participants will be followed for 36 months from initiation of an oral anticoagulant or will be censored at primary outcome, cessation of oral anticoagulant or death.
Secondary outcome [3] 317816 0
Ability to perform daily tasks assessed using The Lawton Instrumental Activities of Daily Living (IADL) Scale.
IADL will be determined using data from a patient questionnaire on IADL.
Timepoint [3] 317816 0
Participants will be assessed for IADL at baseline (commencement of oral anticaogulant)
Secondary outcome [4] 322231 0
Stroke risk assessed using CHADS2 score.
Stroke risk will be determined using data from medical records and medications.
Timepoint [4] 322231 0
Participants will be assessed for CHADS2 at baseline (commencement of oral anticaogulant)
Secondary outcome [5] 322232 0
Bleeding risk assessed using HAS-BLED score.
Bleeding risk will be determined using data from medical records and medications.
Timepoint [5] 322232 0
Participants will be assessed for HAS-BLED at baseline (commencement of oral anticaogulant)
Secondary outcome [6] 322233 0
Burden of drug use assessed by the drug burden index (DBI).
Drug burden will be determined using data from medical records and medications.
Timepoint [6] 322233 0
Participants will be assessed for DBI at baseline (commencement of oral anticaogulant)

Eligibility
Key inclusion criteria
commencement of an oral anticoagulant in the past 4 weeks
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
previous use of warfarin or other oral anticoagulants in the previous 12 months. severe hearing impairment such that the participant cannot participate in an interview or where the investigator feels that it will not be possible to collect adequate follow-up information.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A recent systematic review of 31 observational studies reported the incidence of bleeding with warfarin use in patients with AF (mean age range 64-83 years), ranged from 0.2-7.6 bleeds per 100 patient-years. Data on the incidence of bleeding in frail patients is scarce. A previous study reported a six-month 30% incidence of major or severe haemorrhage in frail older people aged =70 years who were users of warfarin19 and another more recent study found a six month incidence of 5.8%. We intend to recruit a total of 1,000 patients initiated on an oral anticoagulant, a two-sided log rank test with such a sample size assuming that 40% of the patients will be frail, and 60% non-frail, achieves 80% power at 5% significance level to detect a difference between 5% of the frail group having a major haemorrhage compare to 1% of the non-frail group, allowing for 20% drop out. (PASS 11. NCSS, LLC. Kaysville, Utah, USA).

Competing risks multivariate survival analysis will be used to examine time to event.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2016
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC

Funding & Sponsors
Funding source category [1] 292111 0
Self funded/Unfunded
Name [1] 292111 0
Country [1] 292111 0
Primary sponsor type
Hospital
Name
Clinical Pharmacology, Royal Adelaide Hospital
Address
North Tce, Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 290787 0
None
Name [1] 290787 0
Address [1] 290787 0
Country [1] 290787 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293597 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 293597 0
Level 3, Hanson Institute IMVS Building. North Terrace, Adelaide, South Australia, 5000
Ethics committee country [1] 293597 0
Australia
Date submitted for ethics approval [1] 293597 0
Approval date [1] 293597 0
25/06/2015
Ethics approval number [1] 293597 0
120911

Summary
Brief summary
The primary objective of the study is to investigate whether frailty increases the risk of major haemorrhage / clinically significant non-major bleed in older patients initiating an oral anticoagulant. The secondary objectives are to investigate whether frailty is a risk factor for cessation of oral anticoagulants, stroke / VTE and the association between pharmacological risk factors ability to predict the primary and secondary outcomes will be investigated in frail and non-frail participants.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60618 0
Dr Sepehr Shakib
Address 60618 0
Clinical Pharmacology, Level 7 Emergency Block, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000 and University of Adelaide, Medical School South, Discipline of Clinical Pharmacology, Frome Rd, Adelaide, South Australia, 5000
Country 60618 0
Australia
Phone 60618 0
+61882222763
Fax 60618 0
Email 60618 0
[email protected]
Contact person for public queries
Name 60619 0
Gillian Caughey
Address 60619 0
Clinical Pharmacology, Level 7 Emergency Block, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000
Country 60619 0
Australia
Phone 60619 0
+61882222763
Fax 60619 0
Email 60619 0
[email protected]
Contact person for scientific queries
Name 60620 0
Gillian Caughey
Address 60620 0
Clinical Pharmacology, Level 7 Emergency Block, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000
Country 60620 0
Australia
Phone 60620 0
+61882222763
Fax 60620 0
Email 60620 0
[email protected]

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

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