Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000116628
Ethics application status
Approved
Date submitted
16/01/2023
Date registered
3/02/2023
Date last updated
29/07/2024
Date data sharing statement initially provided
3/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The acute effects of glyceryl trinitrate (GTN) on exercise capacity in patients who have an implantable cardiac pump (LVAD)
Scientific title
The Acute Effects of Translingual Glyceryl Trinitrate (GTN) on Exercise Parameters in Patients with Left Ventricular Assist Devices
Secondary ID [1] 308767 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart failure 328713 0
Condition category
Condition code
Cardiovascular 325723 325723 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cardiopulmonary Test:
• Cardiopulmonary exercise testing (CPET) will be performed on an upright bicycle ergometer using a ramp protocol, limited by fatigue. Resistance will be increased every 3 minutes.
• Breath-by-breath expired gas analysis will be measured by indirect calorimetry using a calibrated metabolic analysis system
• Ventilatory anaerobic threshold (VAT) will be determined as the breakpoint between the increase in the carbon dioxide output and VO2 (V-slope) or the point at which the ventilator equivalent for oxygen and end-tidal oxygen partial pressure curves reach their respective minimum values and began to rise.
• The test will be interrupted when the participant can no longer maintain the exercise intensity, ideally after maximal respiratory exchange ratio is greater than or equal to 1.1.
• VO2 peak will be calculated as the highest 30 second average VO2 recorded during the exercise test.
• Test duration will be 10-15 minutes
• Subjects will undergo 2 CPETs in in total, 7-70 days apart
o First CPET with GTN (Group A) or placebo (Group B)
o Second CPET with GTN (Group B) or placebo (GroupA)


Echocardiogram:
• All patients will undergo a transthoracic echocardiogram prior to the CPET to ensure their pump speed is optimised. The goals are to achieve a midline interventricular septum position, reduction in mitral regurgitation and intermittent aortic valve opening.

Blinded 6MWT:
It should be noted that the randomisation for this part of the study is independent from the CPET randomisation.
Tests will be conducted according to the 2002 American Thoracic Society guidelines, performed on two separate days (7-28 days apart).
The test should take approximately 15 minutes.
Patients will perform a test with placebo and a test with GTN, in a randomised order. The test should take approximately 15 minutes.
Patients will be consented for both the CPET tests and the 6MWTs. Patients will undergo all tests(CPETs and 6MWTs) or one of them, depending on their availability.

6MWTs with placebo:
• Randomisation will take place prior to test start.
• Subject and nurse responsible for supervising 6MWT will record BP, oxygen saturation. They should remain blinded to pump speed setting.
• Responsible physician is to remain available for duration of 6MWT but must not be involved in the conduct of the test.
• Subjects will receive a translingual placebo dose 5 minutes prior to test initiation
• At the end of the 6 minutes, record the distance covered, heart rate, oxygen saturation and Borg Fatigue score.
6MWTs with GTN (performed on a different day):
• Randomisation will take place prior to test start.
• Data collected will be same as described above.
• Subjects will receive 400mcg of translingual GTN 5 minutes prior to test initiation
• This step of the study will only take place if the mean arterial pressure of the subject is less than 70mmHg.
• Both 6MWTs will be separated by at least 48 hours from the CPETs

Dispensing of study drug:
• Participants will be randomized to study drug vs placebo after enrolment. The study drug (active and placebo) will be obtained from St Vincent’s Hospital as discussed with the Clinical Trials Unit.
• A health care worker not directly involved with the study will be responsible for administering the drug/placebo. Patients and supervising physicians will be blind to the administered drug.
• Subjects will receive either 400mcg of translingual GTN 5 minutes prior to test initiation or placebo, in a randomised order. The study drug (active and placebo) will be obtained from St Vincent’s Hospital pharmacy. The placebo component will be made from peppermint water, which has a similar taste to translingual GTN. The spray containers will not be identical. To account for this and maintain blinding, patients will be blindfolded prior to drug administration. The drug will be administered by a healthcare professional that is not directly involved with the study.
Intervention code [1] 325218 0
Treatment: Drugs
Comparator / control treatment
Placebo made from peppermint water, which has a similar taste to translingual GTN
Patients will be their own controls
Control group
Placebo

Outcomes
Primary outcome [1] 333570 0
Difference in peak VO2 between the cardiopulmonary tests with GTN and placebo, as assessed using a cardiometabolic cart
Timepoint [1] 333570 0
First CPET session and second CPET session (7-28 days apart)
Primary outcome [2] 333571 0
Distance completed during 6 minute walk test, measured in a corridor with a known distance
Timepoint [2] 333571 0
First 6 minute walk test and second 6 minute walk test (7-28 days apart).
These tests occur in parallel with the CPETs and no specific timeframe has been specified relative to the performance of the CPETs.
Secondary outcome [1] 417564 0
Difference in exercise duration during CPET, as measured by the integrated bicycle ergometer/computer software
Timepoint [1] 417564 0
First CPET session and second CPET session (7-28 days apart)
Secondary outcome [2] 417565 0
Difference in ventilatory efficiency (Ve/VCO2 slope), as assessed by the cardio metabolic cart during CPET
Timepoint [2] 417565 0
First CPET session and second CPET session (7-28 days apart)
Secondary outcome [3] 417566 0
Difference in fatigue levels as assessed by Borg Scale
Timepoint [3] 417566 0
First 6 minute walk test and second 6 minute walk test (7-28 days apart)

Eligibility
Key inclusion criteria
• Willingness to give written informed consent and willingness to participate to and comply with the study.
• Age greater or equal to 18
• Clinically stable: no new additional disease-modifying drug (angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, sacubitril, beta-blocker), no change in disease-modifying drug dosage more than 50% (excluded: diuretics), no recent (previous 3 months) admission to the hospital with decompensated heart failure.
• Ambulatory.
• >8 weeks after pump insertion.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Active, uncontrolled infection.
• Exercise induced myocardial ischaemia or significant arrhythmias.
• Recent acute coronary syndrome (<6 weeks).
• Limiting musculoskeletal disorder.
• Poor exercise capacity on 6MWT
• Significant lung disease that is likely to limit exercise capacity
• Exercise induced asthma
• Regular sildenafil use.
• Hypotension (mean arterial pressure <65mmHg)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes, prepared by a researcher not involved with the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated block randomisation. Study investigators are blind to to the block sizes and order.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Paired samples t-test will be used for normally distributed variables. Wilcoxon signed-rank test will be used for non-parametric variables. For unpaired data, t-test for normally distributed variables, Wilcoxon rank-sum test for non-parametric variables and Fisher’s exact test for unpaired categorical data will be used to compare independent samples.
Results will be presented as means with 95% confidence intervals (CIs), mean SD, or median and interquartile range, as appropriate. A p value of < 0.05 will be considered statistically significant. Statistical analysis will be conducted using R studio (R Core Team 2022, R foundation for Statistical Computing, Vienna, Austria) version 2022.07.1-554 (or later if updates become available)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/02/2023
Actual
22/03/2023
Date of last participant enrolment
Anticipated
1/11/2024
Actual
Date of last data collection
Anticipated
6/01/2025
Actual
Sample size
Target
20
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23842 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 39297 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 312990 0
Charities/Societies/Foundations
Name [1] 312990 0
MCS research trust fund (242058)
Country [1] 312990 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Sydney
Address
390 Victoria Street, Darlinghurst. 2010, NSW
Country
Australia
Secondary sponsor category [1] 314673 0
None
Name [1] 314673 0
Address [1] 314673 0
Country [1] 314673 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312253 0
St Vincent's Hosital Sydney Human Ethics Committee
Ethics committee address [1] 312253 0
Ethics committee country [1] 312253 0
Australia
Date submitted for ethics approval [1] 312253 0
21/09/2022
Approval date [1] 312253 0
07/12/2022
Ethics approval number [1] 312253 0
2022/STE02304

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

Contacts
Principal investigator
Name 124002 0
Prof Christopher Hayward
Address 124002 0
Cardiology Department St Vincent's Hospital 390 Victoria Street Darlinghurst, 2010 NSW
Country 124002 0
Australia
Phone 124002 0
+61 0409575454
Fax 124002 0
Email 124002 0
[email protected]
Contact person for public queries
Name 124003 0
Ricardo Deveza e Silva
Address 124003 0
Cardiology Department St Vincent's Hospital 390 Victoria Street Darlinghurst, 2010 NSW
Country 124003 0
Australia
Phone 124003 0
+61 283823052
Fax 124003 0
Email 124003 0
[email protected]
Contact person for scientific queries
Name 124004 0
Ricardo Deveza e Silva
Address 124004 0
Cardiology Department St Vincent's Hospital 390 Victoria Street Darlinghurst, 2010 NSW
Country 124004 0
Australia
Phone 124004 0
+61 283823052
Fax 124004 0
Email 124004 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


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.