Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000658112p
Ethics application status
Submitted, not yet approved
Date submitted
29/03/2019
Date registered
2/05/2019
Date last updated
2/05/2019
Date data sharing statement initially provided
2/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II Randomised, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Oral NP202 in Reducing the Incidence of Atrial Fibrillation in Adults who have undergone Cardiac Surgery.
Scientific title
A Phase II Randomised, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Oral NP202 in Reducing the Incidence of Atrial Fibrillation in Adults who have undergone Cardiac Surgery.
Secondary ID [1] 297648 0
NP202-004
Universal Trial Number (UTN)
U1111-1229-6733
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation
 311921 0
Cardiac bypass graft surgery 311922 0
valve surgery
 311923 0
Condition category
Condition code
Cardiovascular 310510 310510 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
NP202
1,000mg by oral capsule once daily, for up to 10 days Treatment will begin 3 days prior to the scheduled surgery and continue discharge from hospital. Adherence will be monitored by unused capsule return and observation by study personnel.
Intervention code [1] 313882 0
Prevention
Comparator / control treatment
Placebo, which will be, microceullose capsules
Control group
Placebo

Outcomes
Primary outcome [1] 319367 0
Incidence of post-operative atrial fibrillation, defined as any episode lasting longer than 30 seconds, as measured by the ICU bedside monitor
Timepoint [1] 319367 0
By 7 days post surgery, or discharge from hospital, whichever comes first
Secondary outcome [1] 367915 0
• Time of onset of atrial fibrillation in relation to time of surgery, as measured by the ICU bedside monitor
Timepoint [1] 367915 0
By 7 days post surgery, or discharge from hospital, whichever comes first
Secondary outcome [2] 368943 0
Duration of atrial fibrillation episodes, as measured by the ICU bedside monitor
Timepoint [2] 368943 0
By 7 days post surgery, or discharge from hospital, whichever comes first
Secondary outcome [3] 368944 0
Requirement for pharmacological management of atrial fibrillation episodes, as assessed by recording of concomitant medications from hospital records
Timepoint [3] 368944 0
By 7 days post surgery, or discharge from hospital, whichever comes first
Secondary outcome [4] 368945 0
Requirement for inotropic drug use post-surgery, as assessed by recording of concomitant medications from hospital records
Timepoint [4] 368945 0
By 7 days post surgery, or discharge from hospital, whichever comes first
Secondary outcome [5] 368946 0
Change from the area under the curve (AUC) of troponin-I measured over 24 hours post-surgery, as assessed by serial serum assays
Timepoint [5] 368946 0
Blood samples for measurement of troponin-I levels will be collected pre, immediately post, and at 4, 8, 12, 24, and 48 hours post-surgery
Secondary outcome [6] 368947 0
Cardiac index over 12 hours post-surgery, as measured by the ICU bedside monitor
Timepoint [6] 368947 0
By 7 days post surgery, or discharge from hospital, whichever comes first

Eligibility
Key inclusion criteria
• Are male or female and aged at least 70 years old at the time of consent.
• Are scheduled for coronary arterial bypass graft and/or valve replacement surgery
• Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements.
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Clinical history of chronic or paroxysmal atrial fibrillation.
• Estimated glomerular filtration rate (eGFR) <30ml/min
• Have received any investigational research agent within 30 days or 5 half-lives (whichever is longer) prior to the first dose of IP.
• History of severe or life-threatening drug allergy and/or known drug hypersensitivity.
• Current malignancy or previous malignancy that is likely to recur during the period of the study (with the exception of a past history of basal or squamous cell carcinomas).
• Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C (note these will not be tested for)
• Other than the protocol indication, history of or current clinically significant gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunodeficiency, neurological, metabolic, haematological, autoimmune or psychological disorder that, in the investigator’s opinion, would compromise subject safety or protocol compliance

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)
Allocation is concealed. Allocation is central and randomized
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary efficacy endpoint is the incidence of post-operative atrial fibrillation.
The primary analysis will be performed using a two-sided Cochran-Mantel-Haenszel (CMH) test with treatment group and surgery type as stratification factors to compare the proportions of subjects with AF (incidence) between the NP202 and Placebo groups. The primary analysis will be based on the modified intention-to-treat analysis set.
The null hypothesis is that there is no difference in the proportion of subjects with AF between the NP202 and Placebo groups. The alternative hypothesis is that there is a difference in the proportion of subjects with AF between the groups.
A sample size of at least 160 subjects achieves 80.2% power to detect a difference of -0.2 between the proportions of the NP202 and Placebo groups. Assuming a Placebo response of 40% (pPlacebo = 0.4), this amounts to a 50% reduction in post-operative AF in the NP202 group compared to Placebo. The sample size was calculated based on a two-sided chi-test at a significance level of 5%.
A total of 180 subjects will be randomised into the study to ensure that at least 160 evaluable subjects.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/06/2019
Actual
Date of last participant enrolment
Anticipated
1/06/2020
Actual
Date of last data collection
Anticipated
30/06/2020
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 13321 0
John Hunter Hospital - New Lambton
Recruitment hospital [2] 13322 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 25921 0
2305 - New Lambton
Recruitment postcode(s) [2] 25922 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 302177 0
Commercial sector/Industry
Name [1] 302177 0
Armaron Bio Ltd
Country [1] 302177 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Armaron Bio Ltd
Address
86 Denmark St
Kew
VIC 3101
Country
Australia
Secondary sponsor category [1] 302019 0
None
Name [1] 302019 0
Address [1] 302019 0
Country [1] 302019 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302859 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 302859 0
Ethics committee country [1] 302859 0
Australia
Date submitted for ethics approval [1] 302859 0
28/02/2019
Approval date [1] 302859 0
Ethics approval number [1] 302859 0

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

Contacts
Principal investigator
Name 91634 0
Prof Rinaldo Bellomo
Address 91634 0
Intensive Care
Austin Hospital
145 Studley Road,
Heidelberg
Victoria 3084
Country 91634 0
Australia
Phone 91634 0
+61-3-94965000
Fax 91634 0
+61-3-94963932
Email 91634 0
[email protected]
Contact person for public queries
Name 91635 0
Grant McLachlan
Address 91635 0
Armaron Bio Ltd
86 Denmark St
Kew VIC 3101
Country 91635 0
Australia
Phone 91635 0
+61396522117
Fax 91635 0
Email 91635 0
[email protected]
Contact person for scientific queries
Name 91636 0
Grant McLachlan
Address 91636 0
Armaron Bio Ltd
86 Denmark St
Kew VIC 3101
Country 91636 0
Australia
Phone 91636 0
+61 438356071
Fax 91636 0
Email 91636 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
This is a small study designed to aid in further development studies and individual participant results are not useful to the participants nor others outside of the sponsor.


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.