Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001521718
Ethics application status
Approved
Date submitted
24/11/2022
Date registered
7/12/2022
Date last updated
14/01/2024
Date data sharing statement initially provided
7/12/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Multivessel compared to Single Vessel Functional Angiography to Diagnose Patients with No Obstructive Coronary Artery Disease: The MAD-NOCA trial
Scientific title
Multivessel compared to single vessel functional angiography to diagnose a disorder of coronary vasomotion and predict clinical outcomes in patients with no obstructive coronary artery disease: The MAD-NOCA trial
Secondary ID [1] 308571 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The MAD-NOCA trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Angina 328298 0
Coronary ischaemia 328299 0
Condition category
Condition code
Cardiovascular 325349 325349 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Multivessel functional angiography
- Qualified study personnel will complete coronary physiology and vasoreactivity testing (with intracoronary acetylcholine) to assess the coronary microcirculation and propensity for coronary vasospasm. Vasoreactivity testing will include incremental doses of acetylcholine (20/50/100/200mcg into the left coronary system and 20/50/80mcg into the right coronary system, respectively)
- All 3 major epicardial coronary arteries (left anterior descending, left circumflex and right coronary artery) will be assessed.
- This intervention will occur in the cardiology catheterization lab and be delivered once during the study period.
- The intervention will take approximately 45 minutes to complete
Intervention code [1] 324925 0
Diagnosis / Prognosis
Comparator / control treatment
Single vessel functional angiography
- Qualified study personnel will complete coronary physiology and vasoreactivity testing (with intracoronary acetylcholine) to assess the coronary microcirculation and propensity for coronary vasospasm.
- Only 1 epicardial coronary artery (at the operator's discretion) will be assessed.
- This intervention will occur in the cardiology catheterization lab and be delivered once during the study period.
- The intervention will take approximately 30 minutes to complete
Control group
Active

Outcomes
Primary outcome [1] 333206 0
Seattle angina questionnaire (SAQ) score
Timepoint [1] 333206 0
6 months (primary endpoint) and 12 months post-angiography
Primary outcome [2] 333256 0
The proportion of patients diagnosed with a disorder of coronary vasomotion.
- This will be based on coronary angiographic criteria through a review of this angiographic data.
Timepoint [2] 333256 0
6 months (primary endpoint) and 12 months post-angiography
Secondary outcome [1] 416166 0
Incidence of major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke/TIA or hospitalization for heart failure or angina
Method of assessment: medical record review and participant self-reporting
Timepoint [1] 416166 0
6 months and 12 months post-angiography.
Secondary outcome [2] 416367 0
Incidence of all-cause mortality
Method of assessment: medical record review and participant self-reporting
Timepoint [2] 416367 0
6 months and 12 months post-angiography.
Secondary outcome [3] 416368 0
Incidence of non-fatal myocardial infarction.
Method of assessment: medical record review and participant self-reporting.
Timepoint [3] 416368 0
6 months and 12 months post-angiography.
Secondary outcome [4] 416369 0
Incidence of non-fatal stroke/TIA.
Method of assessment: medical record review and participant self-reporting.
Timepoint [4] 416369 0
6 months and 12 months post-angiography.
Secondary outcome [5] 416370 0
Incidence of hospitalization for heart failure or angina
Method of assessment: medical record review and participant self-reporting.
Timepoint [5] 416370 0
6 months and 12 months post-angiography.
Secondary outcome [6] 416371 0
Incidence of cardiovascular mortality.
Method of assessment: medical record review and participant self-reporting.
Timepoint [6] 416371 0
6 months and 12 months post-angiography.
Secondary outcome [7] 416373 0
Limitations caused by angina using Seattle Angina Questionnaire (SAQ).
Timepoint [7] 416373 0
6 months and 12 months post-angiography.
Secondary outcome [8] 416374 0
General health status and self-reported quality of life using the Euro-QoL-5D (EQ5D).
Timepoint [8] 416374 0
6 months and 12 months post-angiography.
Secondary outcome [9] 416375 0
Self-reported levels of treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM).
Timepoint [9] 416375 0
6 months and 12 months post-angiography.
Secondary outcome [10] 416376 0
Perception of their illness using the Brief Illness Perception Questionnaire (IPQ-B).
Timepoint [10] 416376 0
6 months and 12 months post-angiography.
Secondary outcome [11] 416377 0
Impact of disclosure of the coronary function test results on medical decisions (including treatment and investigations).
Method of assessment: medical record review and participant self-reporting.
Timepoint [11] 416377 0
6 months and 12 months post-angiography.
Secondary outcome [12] 416379 0
Assess resource utilisation, including primary and secondary care costs for tests, procedures and outpatient visits and medicines between groups.
Method of assessment: medical record review and accessing hospital administrative data
Timepoint [12] 416379 0
6 months and 12 months post-angiography.
Secondary outcome [13] 416579 0
Self-reported levels of anxiety and depression using the Patient Health Questionnaire-4 (PHQ-4)
Timepoint [13] 416579 0
6 months and 12 months post-angiography.

Eligibility
Key inclusion criteria
• Adult men and women aged over 18
• Clinically referred for coronary angiography
• Coronary angiography diagnosis of non-obstructive coronary arteries (<50% stenosis of a major epicardial vessel or a FFR >0.8)
• Acute or subacute ischemic symptoms such as chest pain or anginal equivalent symptoms at rest or new onset exertional angina
• Symptoms of atypical chest pain which is difficult to characterise
• Underlying diagnosis of a cardiomyopathy, valvular heart disease or arrhythmia
• Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances
• Able to personally read and understand the Participant Information and Consent Form and provide written, signed and data informed consent to participate in study (health care interpreters will be engaged for people with cultural and linguistically diverse backgrounds).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Cardiogenic shock
• Coronary angiography revealing obstructive coronary arteries (above or equal to 50% stenosis)
• Myocardial infarction within 7 days
• Severe obstructive airways – any prior admission to ICU or general hospital admission in the past 12 months for infective exacerbation of airways disease.
• Active internal bleeding or history of haemorrhagic diathesis (including heparin-induced thrombocytopenia)
• Recent use of vasospastic agents, such as cocaine, triptans, or ergot alkaloids (less than or equal to 1 month)
• Major Surgery (e.g., Coronary Artery Bypass Graft [CABG]) or trauma within the previous 6 weeks
• Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration (this is routine practice prior to coronary angiography).
• Inability to provide informed consent (compromised mental status e.g., dementia, too ill) for clinically indicated coronary angiography
• Currently a prisoner (has been admitted to hospital via a correctional facility)
• Contraindications to drugs and devices (Adenosine, Glyceryl Trinitrate [GTN], Acetylcholine)
• Heavily calcified or tortuous vessels leading to inability to advance pressure wire

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation completed by central randomisation software
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
17/03/2022
Date of last participant enrolment
Anticipated
1/06/2024
Actual
Date of last data collection
Anticipated
1/07/2025
Actual
Sample size
Target
72
Accrual to date
64
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23640 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 23641 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 39060 0
2139 - Concord
Recruitment postcode(s) [2] 39061 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 312731 0
Hospital
Name [1] 312731 0
Concord Hospital - Cardiology Department
Country [1] 312731 0
Australia
Funding source category [2] 312775 0
Hospital
Name [2] 312775 0
Royal Prince Alfred Hospital
Country [2] 312775 0
Australia
Primary sponsor type
Hospital
Name
Concord Repatriation General Hospital
Address
Hospital Rd, Concord NSW 2139
Country
Australia
Secondary sponsor category [1] 314407 0
None
Name [1] 314407 0
N/A
Address [1] 314407 0
N/A
Country [1] 314407 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312027 0
Sydney Local Health District HREC - Concord Repatriation General Hospital
Ethics committee address [1] 312027 0
Ethics committee country [1] 312027 0
Australia
Date submitted for ethics approval [1] 312027 0
Approval date [1] 312027 0
17/01/2022
Ethics approval number [1] 312027 0

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

Contacts
Principal investigator
Name 123226 0
Prof Andy Yong
Address 123226 0
Concord Repatriation General Hospital, Hospital Road, Concord NSW 2139
Country 123226 0
Australia
Phone 123226 0
+61029767 8390
Fax 123226 0
Email 123226 0
[email protected]
Contact person for public queries
Name 123227 0
Andy Yong
Address 123227 0
Concord Repatriation General Hospital, Hospital Road, Concord NSW 2139
Country 123227 0
Australia
Phone 123227 0
+61029767 8390
Fax 123227 0
Email 123227 0
[email protected]
Contact person for scientific queries
Name 123228 0
Andy Yong
Address 123228 0
Concord Repatriation General Hospital, Hospital Road, Concord NSW 2139'
Country 123228 0
Australia
Phone 123228 0
+61029767 8390
Fax 123228 0
Email 123228 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual de-identified participant data underlying published results only.
When will data be available (start and end dates)?
Immediately following publication and ending 5 years following main results publication.
Available to whom?
Case-by-case basis at the discretion of the Primary Sponsor
Available for what types of analyses?
Only to achieve the aims of the approved proposal
How or where can data be obtained?
Access is subject to approvals by Principal Investigator. Email: [email protected]


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.